Cholera studies*†

PubMed Central

Pollitzer, R.; Burrows, W.

1955-01-01

Relevant information regarding the numerous problems encountered in cholera immunity is dealt with in great detail in this study. Toxin production, bacterial virulence, serological reactions, and the antigenic structure of V. cholerae are discussed. Natural, passive, and active cholera immunity receives special attention, the authors describing the various means of vaccination as well as the evaluation of the immunity induced. PMID:13240451

Immune-based therapies.

PubMed

Lein, B

1995-12-01

Several immune-based HIV therapy studies presented at the Interscience Conference on Antimicrobial Agents Chemotherapy (ICAAC) are summarized. These studies involve the following therapies: HIV-IT, a gene therapy approach to augmenting the body's anti-HIV responses; interferon-alpha n3, a new formulation of alpha interferon with fewer toxicities; transfer of immune responses from one individual to another, also called passive immune therapy; and interleukin-2 (IL-2) in combination with protease inhibitors.

A global survey of adverse event following immunization surveillance systems for pregnant women and their infants.

PubMed

Cassidy, Christine; MacDonald, Noni E; Steenbeek, Audrey; Ortiz, Justin R; Zuber, Patrick L F; Top, Karina A

2016-08-02

Strengthening antenatal care as a platform for maternal immunization is a priority of the World Health Organization (WHO). Systematic surveillance for adverse events following immunization (AEFI) in pregnancy is needed to identify vaccine safety events. We sought to identify active and passive AEFI surveillance systems for pregnant women and infants. Representatives from all National Pharmacovigilance Centers and a convenience sample of vaccine safety experts were invited to complete a 14-item online survey in English, French or Spanish. The survey captured maternal immunization policies, and active and passive AEFI surveillance systems for pregnant women and infants in respondents' countries. The analysis was descriptive. We received responses from 51/185 (28%) invited persons from 47/148 (32%) countries representing all WHO regions, and low, middle and high-income countries. Thirty countries had national immunization policies targeting pregnant women. Eleven countries had active surveillance systems to detect serious AEFI in pregnant women and/or their infants, including six low and middle-income countries (LMIC). Thirty-nine countries had passive surveillance systems, including 23 LMIC. These active and passive surveillance programs cover approximately 8% and 56% of the worldwide annual birth cohort, respectively. Data from one active and four passive systems have been published. We identified 50 active and passive AEFI surveillance systems for pregnant women and infants, but few have published their findings. AEFI surveillance appears to be feasible in low and high resource settings. Further expansion of AEFI surveillance for pregnant women and sharing of vaccine safety information will provide additional evidence in support of maternal immunization policies.

Equine Immunoglobulin and Equine Neutralizing F(ab')₂ Protect Mice from West Nile Virus Infection.

PubMed

Cui, Jiannan; Zhao, Yongkun; Wang, Hualei; Qiu, Boning; Cao, Zengguo; Li, Qian; Zhang, Yanbo; Yan, Feihu; Jin, Hongli; Wang, Tiecheng; Sun, Weiyang; Feng, Na; Gao, Yuwei; Sun, Jing; Wang, Yanqun; Perlman, Stanley; Zhao, Jincun; Yang, Songtao; Xia, Xianzhu

2016-12-18

West Nile virus (WNV) is prevalent in Africa, Europe, the Middle East, West Asia, and North America, and causes epidemic encephalitis. To date, no effective therapy for WNV infection has been developed; therefore, there is urgent need to find an efficient method to prevent WNV disease. In this study, we prepared and evaluated the protective efficacy of immune serum IgG and pepsin-digested F(ab')₂ fragments from horses immunized with the WNV virus-like particles (VLP) expressing the WNV M and E proteins. Immune equine F(ab')₂ fragments and immune horse sera efficiently neutralized WNV infection in tissue culture. The passive transfer of equine immune antibodies significantly accelerated the virus clearance in the spleens and brains of WNV infected mice, and reduced mortality. Thus, equine immunoglobulin or equine neutralizing F(ab')₂ passive immunotherapy is a potential strategy for the prophylactic or therapeutic treatment of patients infected with WNV.

Protection of rats against dental caries by passive immunization with hen-egg-yolk antibody (IgY).

PubMed

Otake, S; Nishihara, Y; Makimura, M; Hatta, H; Kim, M; Yamamoto, T; Hirasawa, M

1991-03-01

Hen-egg-yolk antibody (IgY) was prepared against Streptococcus mutans MT8148 serotype c that was cultivated in medium containing sucrose, and it was used in passive caries-immunity studies. Specific pathogen-free rats infected with S. mutans MT8148 (c) and fed with a cariogenic diet containing more than 2% immune yolk powder developed significantly lower caries scores than did the ones infected with the same strain and fed with a diet containing only control yolk powder obtained from non-immunized hens. Similar results were obtained in an experiment with rats infected with S. mutans JC-2 (c) strain. Rats provided a diet supplemented with 0.5% immune water-soluble protein fraction containing S. mutans-specific IgY and challenged with S. mutans MT8148 exhibited significantly fewer caries lesions, compared with control rats on the normal diet.

Effectiveness analyses may underestimate protection of infants after group C meningococcal immunization.

PubMed

Vu, David M; Kelly, Dominic; Heath, Paul T; McCarthy, Noel D; Pollard, Andrew J; Granoff, Dan M

2006-07-15

Group C meningococcal conjugate-vaccine effectiveness in the United Kingdom declines from ~90% in the first year to 0% between 1 and 4 years after immunization in infants immunized at 2, 3, and 4 months of age and to 61% in toddlers given a single dose. Confidence intervals are wide, and the extent of protection is uncertain. Serum samples were obtained from children 3-5 years of age who were participants in a preschool booster-vaccine trial. Serum bactericidal activity was measured with human complement. Group C anticapsular antibody concentrations were measured by a radioantigen binding assay. Passive protection was analyzed in an infant rat bacteremia model. Serum samples from UK children who had been immunized 2-3 years earlier as infants or toddlers had higher levels of radioantigen binding, bactericidal activity, and passive protection than did historical control serum samples from unimmunized children (P<.05). A higher proportion of children immunized as infants had serum bactericidal activity titers > or =1 : 4 (considered to be protective) than those immunized as toddlers (61% vs. 24%; P<.01), but there were no significant differences in the proportion of serum samples conferring passive protection (50% and 41%, respectively; P=.4). We found no evidence of lower immunity in children immunized as infants than as toddlers. On the basis of serum bactericidal activity and/or passive protection, 40%-50% of both age groups are protected at 2-3 years after immunization, which was significantly greater than in unimmunized historical controls (<5%).

79 FR 4730 - Government-Owned Inventions; Availability for Licensing

Federal Register 2010, 2011, 2012, 2013, 2014

2014-01-29

... patent applications. Novel Targets To Prevent Borrelia burgdorferi Infection and Lyme Disease Description... B. burgdorferi infection by passive immunity and provide new diagnostic tools, which will allow.... burgdorferi diagnostics Prevention of B. burgdorferi infection by passive immunity Zoonotic/tick-borne disease...

Passive immunity in transmissible gastroenteritis of swine: immunoglobulin characteristics of antibodies in milk after inoculating virus by different routes.

PubMed Central

Bohl, E H; Saif, L J

1975-01-01

Pregnant swine were exposed to transmissible gastroenteritis (TGE) virus by different routes, and their serum, colostrum, and mild were examined for titer and immunoglobulin (Ig) class of antibodies. When 2 to 4 days old, the litters of most of these animals were challenged with virulent TGE virus to determine the effectiveness of passive immunity. After two oral/intranasal exposures to attenuated virus, none of the six pregnant animals became sick. TGE antibodies in milk were primarily or solely of the IgG class, although low levels of IgA antibodies were detected in three animals. Pigs in the five challenged litters received some passive immunity, the mortality being 25%. After intramuscular injection of six pregnant swine with virulent virus, two types of clinical and immunological responses were observed, presumably dependent on whether the gut was infected by an hematogenous spread of the virus. Three became sick, showing typical clinical signs of TGE, and their immunological response was characterized by the occurrence in milk of antibodies of the IgA class. A good degree (0% mortality) of passive immunity occurred upon challenge of the suckling pigs. In contrast, in three pregnant animals that did not sicken, antibody in milk was primarily of the IgG calss, and poor (69% mortality) passive immunity occurred. After intramammary injections of three pregnant swine with virulent virus, no sickness was observed and the immunological response was characterized by the occurrence in colostrum of high titers of TGE antibodies that were primarily or solely of the IgG class; good (0% mortality) passive immunity occured. The occurrence in milk of TGE antibodies of the IgA class was associated with an intestinal infection, whereas antibodies of the IgG class resulted from a parenteral antigenic stimulation. The role of antigenic stimulation of the intestinal tract for providing antibodies in milk of the IgA class is discussed. Passive immunity against intestinal infection with TGE virus was generally more complete in pigs ingesting antibodies of the IgA than of the IgG class. PMID:803922

Effects of IgY antibody on the development of Marek's disease.

PubMed

Kermani-Arab, V; Moll, T; Cho, B R; Davis, W C; Lu, Y S

1976-01-01

The effects of passive immunization with immunoglobulin Y (IgY) on the pathogenesis of Marek's disease (MD) were examined in an experimental line of White Leghorn chickens highly susceptible to MD. Purified IgY with anti-MDV antibody activity, when injected into chicks, delayed the development of MDV viremia and lesions until 9 days postinoculation (PI) with Marek's disease virus (MDV). The blastogenic response of spleen cells to concanavallin-A was depressed at 6 days PI in the birds without passive immunization, whereas it was not totally depressed until 17 days in birds passively immunized with IgY anti-MDV antibody.

Immunological correlates for protection against intranasal challenge of Bacillus anthracis spores conferred by a protective antigen-based vaccine in rabbits.

PubMed

Weiss, Shay; Kobiler, David; Levy, Haim; Marcus, Hadar; Pass, Avi; Rothschild, Nili; Altboum, Zeev

2006-01-01

Correlates between immunological parameters and protection against Bacillus anthracis infection in animals vaccinated with protective antigen (PA)-based vaccines could provide surrogate markers to evaluate the putative protective efficiency of immunization in humans. In previous studies we demonstrated that neutralizing antibody levels serve as correlates for protection in guinea pigs (S. Reuveny et al., Infect. Immun. 69:2888-2893, 2001; H. Marcus et al., Infect. Immun. 72:3471-3477, 2004). In this study we evaluated similar correlates for protection by active and passive immunization of New Zealand White rabbits. Full immunization and partial immunization were achieved by single and multiple injections of standard and diluted doses of a PA-based vaccine. Passive immunization was carried out by injection of immune sera from rabbits vaccinated with PA-based vaccine prior to challenge with B. anthracis spores. Immunized rabbits were challenged by intranasal spore instillation with one of two virulent strains (strains Vollum and ATCC 6605). The immune competence was estimated by measuring the level of total anti-PA antibodies, the neutralizing antibody titers, and the conferred protective immunity. The results indicate that total anti-PA antibody titers greater than 1 x 10(5) conferred protection, whereas lower titers (between 10(4) and 10(5)) provided partial protection but failed to predict protection. Neutralizing antibody titers between 500 and 800 provided partial protection, while titers higher than 1,000 conferred protection. In conclusion, this study emphasizes that regardless of the immunization regimen or the time of challenge, neutralizing antibody titers are better predictors of protection than total anti-PA titers.

Protective immunity to Japanese encephalitis virus associated with anti-NS1 antibodies in a mouse model.

PubMed

Li, Yize; Counor, Dorian; Lu, Peng; Duong, Veasna; Yu, Yongxin; Deubel, Vincent

2012-07-24

Japanese encephalitis virus (JEV) is a major mosquito-borne pathogen that causes viral encephalitis throughout Asia. Vaccination with an inactive JEV particle or attenuated virus is an efficient preventative measure for controlling infection. Flavivirus NS1 protein is a glycoprotein secreted during viral replication that plays multiple roles in the viral life cycle and pathogenesis. Utilizing JEV NS1 as an antigen in viral vectors induces a limited protective immune response against infection. Previous studies using E. coli-expressed JEV NS1 to immunize mice induced protection against lethal challenge; however, the protection mechanism through cellular and humoral immune responses was not described. JEV NS1 was expressed in and purified from Drosophila S2 cells in a native glycosylated multimeric form, which induced T-cell and antibody responses in immunized C3H/HeN mice. Mice vaccinated with 1 μg NS1 with or without water-in-oil adjuvant were partially protected against viral challenge and higher protection was observed in mice with higher antibody titers. IgG1 was preferentially elicited by an adjuvanted NS1 protein, whereas a larger load of IFN-γ was produced in splenocytes from mice immunized with aqueous NS1. Mice that passively received anti-NS1 mouse polyclonal immune sera were protected, and this phenomenon was dose-dependent, whereas protection was low or delayed after the passive transfer of anti-NS1 MAbs. The purified NS1 subunit induced protective immunity in relation with anti-NS1 IgG1 antibodies. NS1 protein efficiently stimulated Th1-cell proliferation and IFN-γ production. Protection against lethal challenge was elicited by passive transfer of anti-NS1 antisera, suggesting that anti-NS1 antibodies play a substantial role in anti-viral immunity.

Evaluation of humoral and cell-mediated inducible immunity to Haemophilus ducreyi in an animal model of chancroid.

PubMed Central

Desjardins, M; Filion, L G; Robertson, S; Kobylinski, L; Cameron, D W

1996-01-01

To study the mechanisms of inducible immunity to Haemophilus ducreyi infection in the temperature-dependent rabbit model of chancroid, we conducted passive immunization experiments and characterized the inflammatory infiltrate of chancroidal lesions. Polyclonal immunoglobulin G was purified from immune sera raised against H. ducreyi 35000 whole-cell lysate or a pilus preparation and from naive control rabbits. Rabbits were passively immunized with 24 or 48 mg of purified polyclonal immunoglobulin G intravenously, followed 24 h after infusion by homologous titered infectious challenge. Despite titratable antibody, no significant difference in infection or disease was observed. We then evaluated the immunohistology of lesions produced by homologous-strain challenge in sham-immunized rabbits and those protectively vaccinated by pilus preparation immunization. Immunohistochemical stains for CD5 and CD4 T-lymphocyte markers were performed on lesion sections 4, 10, 15, and 21 days from infection. Lesions of pilus preparation vaccinees compared with those of controls had earlier infiltration with significantly more T lymphocytes (CD5+) and with a greater proportion of CD4+ T lymphocytes at day 4 (33% +/- 55% versus 9.7% +/- 2%; P = 0.002), corroborating earlier sterilization (5.0 +/- 2 versus 13.7 +/- 0.71 days; P < 0.001) and lesion resolution. Intraepithelial challenge of pilus-vaccinated rabbits with 100 micrograms of the pilus preparation alone produced indurated lesions within 48 h with lymphoid and plasmacytoid infiltration, edema, and extravasation of erythrocytes. We conclude that passive immunization may not confer a vaccine effect in this model and that active vaccination with a pilus preparation induces a delayed-type hypersensitivity skin test response and confers protection through cell-mediated immunity seen as an amplified lymphocytic infiltrate and accelerated maturation of the T-lymphocyte response. PMID:8613391

Patterns of HIV/SIV Prevention and Control by Passive Antibody Immunization.

PubMed

Yamamoto, Hiroyuki; Matano, Tetsuro

2016-01-01

Neutralizing antibody (NAb) responses are promising immune effectors for control of human immunodeficiency virus (HIV) infection. Protective activity and mechanisms of immunodeficiency virus-specific NAbs have been increasingly scrutinized in animals infected with simian immunodeficiency virus (SIV), chimeric simian/human immunodeficiency virus (SHIV) and related viruses. Studies on such models have unraveled a previously underscored protective potential against in vivo immunodeficiency virus replication. Pre-challenge NAb titers feasibly provide sterile protection from SIV/SHIV infection by purging the earliest onset of viral replication and likely modulate innate immune cell responses. Sufficient sub-sterile NAb titers after established infection also confer dose-dependent reduction of viremia, and in certain earlier time frames augment adaptive immune cell responses and even provide rebound-free viral control. Here, we provide an overview of the obtained patterns of SIV/SHIV protection and viral control by various types of NAb passive immunizations and discuss how these notions may be extrapolated to NAb-based clinical control of HIV infection.

Morbidity-mortality and performance evaluation of Brahman calves from in vitro embryo production

PubMed Central

2011-01-01

Background The use of bovine in vitro embryo production (IVP) increases the reproductive potential of genetically superior cows, enabling a larger scale of embryo production when compared with other biotechnologies. However, deleterious effects such as abnormal fetal growth, longer gestation period, increased birth weight, abortion, preterm birth and higher rates of neonatal mortality have been attributed to IVP. The aim of this study was to compare the influence of in vitro embryo production and artificial insemination (AI) on gestation length, complications with birth, birth weight, method of feeding colostrum, passive transfer of immunity, morbidity-mortality, and performance in Brahman calves. Results Whilst gestation length and birth weight were significantly increased in IVP-derived calves, no difference in weaning weight was observed between groups. The passive transfer of immunity (PT), was assessed in IVP (n = 80) and AI (n = 20) groups 24 hours after birth by determination of gamma-glutamyl transferase (GGT) and gammaglobulin activity as well as by quantification of the concentration of total protein in serum. No differences in passive transfer or incidences of dystocia and diseases at weaning were observed between groups. Birth weight, method of feeding colostrum and dystocia were not correlated with PT in either group. Conclusions In this study, in vitro embryo production did not affect the health status, development, or passive transfer of immunity in Brahman calves. PMID:22136315

Passive Immunization Against Poliomyelitis

PubMed Central

Rinaldo, Charles R.

2005-01-01

Poliomyelitis has gone from being one of the worst scourges of the 20th century to nearing eradication in the 21st. This success is well known to be attributable to the Salk inactivated and Sabin attenuated poliovirus vaccines. However, before introduction of these vaccines, William McDowall Hammon of the University of Pittsburgh Graduate School of Public Health led the first major breakthrough in prevention of the disease by using passive immunization in one of the earliest double-blind, placebo-controlled clinical trials. This study provided the first evidence that antibodies to poliovirus could prevent the disease in humans. PMID:15855454

Passive immunization with hyperimmune egg yolk IgY as prophylaxis and therapy for poultry diseases---A review

USDA-ARS?s Scientific Manuscript database

Passive immunization with pathogen-specific egg yolk antibodies (IgY) is emerging as a potential alternative to antibiotics for the treatment and prevention of various human and animal diseases. Laying hens are an excellent source of high-quality polyclonal antibodies, which can be collected noninv...

Immunization of Mice with a Live Transconjugant Shigella Hybrid Strain Induced Th1 and Th17 Cell-Mediated Immune Responses and Confirmed Passive Protection Against Heterologous Shigellae.

PubMed

Nag, D; Koley, H; Sinha, R; Mukherjee, P; Sarkar, C; Withey, J H; Gachhui, R

2016-02-01

An avirulent, live transconjugant Shigella hybrid (LTSHΔstx) strain was constructed in our earlier study by introducing a plasmid vector, pPR1347, into a Shiga toxin gene deleted Shigella dysenteriae 1. Three successive oral administrations of LTSHΔstx to female adult mice produced comprehensive passive heterologous protection in their offspring against challenge with wild-type shigellae. Production of NO and different cytokines such asIL-12p70, IL-1β and IL-23 in peritoneal mice macrophages indicated that LTSHΔstx induced innate and adaptive immunity in mice. Furthermore, production of IFN-γ, IL-10 and IL-17 in LTSH-primed splenic CD4+ T cell suggested that LTSHΔstx may induce Th1 and Th17 cell-mediated immune responses. Exponential increase of the serum IgG and IgA titre against whole shigellae was observed in immunized adult mice during and after the immunization with the highest peak on day 35. Antigen-specific sIgA was also determined from intestinal lavage of immunized mice. The stomach extracts of neonates from immunized mice, mainly containing mother's milk, contained significant levels of anti-LTSHΔstx immunoglobulin. These studies suggest that the LTSHΔstx could be a new live oral vaccine candidate against shigellosis in the near future. © 2015 The Foundation for the Scandinavian Journal of Immunology.

Population dynamics in echinococcosis and cysticercosis: regulation of Taenia hydatigena and T. ovis in lambs through passively transferred immunity.

PubMed

Gemmell, M A; Lawson, J R; Roberts, M G; Griffin, J F

1990-08-01

A comparison has been made of the interactions between passively transferred and actively acquired immunity in regulating populations of Taenia hydatigena and T. ovis. When ewes were grazed prior to parturition under a high infection pressure, immunity was transferred to their offspring for up to 8 weeks. A qualitative difference between the species was the destruction of larval T. ovis prior to their establishment ('pre-encystment immunity') and that of T. hydatigena after they had become established ('post-encystment immunity') in the challenged lambs. The major difference in terms of population regulation between the two parasites was that infection occurred with T. hydatigena but not with T. ovis in those lambs reared from birth for 16 weeks under high infection pressure. Passive, like active immunity, is a density-dependent constraint. It plays an important role in the population regulation of T. ovis, but not of T. hydatigena. This is discussed in terms of transmission in the natural environment, an hypothesis on humoral protection and the need to elucidate pathways of protection when immunization schedules are being evaluated for controlling the taeniid zoonoses.

Active and realistic passive marijuana exposure tested by three immunoassays and GC/MS in urine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mule, S.J.; Lomax, P.; Gross, S.J.

Human urine samples obtained before and after active and passive exposure to marijuana were analyzed by immune kits (Roche, Amersham, and Syva) and gas chromatography/mass spectrometry (GC/MS). Seven of eight subjects were positive for the entire five-day test period with one immune kit. The latter correlated with GC/MS in 98% of the samples. Passive inhalation experiments under conditions likely to reflect realistic exposure resulted consistently in less than 10 ng/mL of cannabinoids. The 10-100-ng/mL cannabinoid concentration range essential for detection of occasional and moderate marijuana users is thus unaffected by realistic passive inhalation.

Ex vivo model of meningococcal bacteremia using human blood for measuring vaccine-induced serum passive protective activity.

PubMed

Plested, Joyce S; Welsch, Jo Anne; Granoff, Dan M

2009-06-01

The binding of complement factor H (fH) to meningococci was recently found to be specific for human fH. Therefore, passive protective antibody activity measured in animal models of meningococcal bacteremia may overestimate protection in humans, since in the absence of bound fH, complement activation is not downregulated. We developed an ex vivo model of meningococcal bacteremia using nonimmune human blood to measure the passive protective activity of stored sera from 36 adults who had been immunized with an investigational meningococcal multicomponent recombinant protein vaccine. Before immunization, human complement-mediated serum bactericidal activity (SBA) titers of > or = 1:4 against group B strains H44/76, NZ98/254, and S3032 were present in 19, 11, and 8% of subjects, respectively; these proportions increased to 97, 22, and 36%, respectively, 1 month after dose 3 (P < 0.01 for H44/76 and S3032). Against the two SBA-resistant strains, NZ98/254 and S3032, passive protective titers of > or = 1:4 were present in 11 and 42% of sera before immunization, respectively, and these proportions increased to 61 and 94% after immunization (P < 0.001 for each strain). Most of the sera with SBA titers of <1:4 and passive protective activity showed a level of killing in the whole-blood assay (>1 to 2 log(10) decreases in CFU/ml during a 90-min incubation) similar to that of sera with SBA titers of > or = 1:4. In conclusion, passive protective activity was 2.6- to 2.8-fold more frequent than SBA after immunization. The ability of SBA-negative sera to kill Neisseria meningitidis in human blood where fH is bound to the bacteria provides further evidence that SBA titers of > or = 1:4 measured with human complement may underestimate meningococcal immunity.

Specific serum antibody responses in channel catfish (Ictalurus punctatus) provide limited protection against Streptococcus ictaluri challenge

USDA-ARS?s Scientific Manuscript database

Passive immunization has been shown to provide a spectrum of protection against certain piscine pathogens, and studies were conducted to determine the role of specific antibodies in immunity to Streptococcus ictaluri. Adult Nile tilapia (Oreochromis niloticus) were injected i.p. with tryptic soy br...

Using Monoclonal Antibodies to Prevent Mucosal Transmission of Epidemic Infectious Diseases

PubMed Central

Zeitlin, Larry; Cone, Richard A.

1999-01-01

Passive immunization with antibodies has been shown to prevent a wide variety of diseases. Recent advances in monoclonal antibody technology are enabling the development of new methods for passive immunization of mucosal surfaces. Human monoclonal antibodies, produced rapidly, inexpensively, and in large quantities, may help prevent respiratory, diarrheal, and sexually transmitted diseases on a public health scale. PMID:10081672

Macrophages largely contribute to heterologous anti-Propionibacterium acnes antibody-mediated protection from Actinobacillus pleuropneumoniae infection in mice.

PubMed

Ma, Qiuyue; Sun, Changjiang; Yang, Feng; Wang, Lei; Qin, Wanhai; Xia, Xiaojing; Feng, Xin; Du, Chongtao; Gu, Jingmin; Han, Wenyu; Lei, Liancheng

2015-03-01

Actinobacillus pleuropneumoniae is the causative agent of acute and chronic pleuropneumonia. Propionibacterium acnes is a facultative anaerobic gram-positive corynebacterium. We have previously found that anti-P. acnes antibodies can prevent A. pleuropneumoniae infections in mice. To investigate the role of macrophages in this process, affinity-purified anti-P. acnes IgG and anti-A. pleuropneumoniae IgG were used in opsonophagocytosis assays. Additionally, the efficacy of passive immunization with P. acnes serum against A. pleuropneumoniae was tested in macrophage-depleted mice. It was found that anti-P. acnes IgG had an effect similar to that of anti-A. pleuropneumoniae IgG (P > 0.05), which significantly promotes phagocytosis of A. pleuropneumoniae by macrophages (P < 0.01). It was also demonstrated that, after passive immunization with anti-P. acnes serum, macrophage-replete mice had the highest survival rate (90%), whereas the survival rate of macrophage-depleted mice was only 40% (P < 0.05). However, macrophage-depleted mice that had been passively immunized with naïve serum had the lowest survival rate (20%), this rate being lower than that of macrophage-replete mice that had been passively immunized with naïve serum. Overall, anti-P. acnes antibodies did not prevent A. pleuropneumoniae infection under conditions of macrophage depletion (P > 0.05). Furthermore, in mice that had been passively immunized with anti-P. acnes serum, macrophage depletion resulted in a greater A. pleuropneumoniae burden and more severe pathological features of pneumonia in lung tissues than occurred in macrophage-replete mice. It was concluded that macrophages are essential for the process by which anti-P. acnes antibody prevents A. pleuropneumoniae infection in mice. © 2015 The Societies and Wiley Publishing Asia Pty Ltd.

Antibodies against viruses: passive and active immunization

PubMed Central

Law, Mansun; Hangartner, Lars

2008-01-01

Summary of recent advances Antibodies, through passive or active immunization, play a central role in prophylaxis against many infectious agents. While neutralization is a primary function of antibodies in protection against most viruses, the relative contribution of Fc-dependent and complement-dependent antiviral activities of antibodies was found to vary between different viruses in recent studies. The multiple hit model explains how antibodies neutralize viruses and recent data on the stoichiometry of antibody neutralization suggest that the organization of viral surface proteins on viruses, in addition to virus size, influences the level of antibody occupancy required for neutralization. These new findings will improve our strategies in therapeutic antibody engineering and rational vaccine design. PMID:18577455

Passive immunization against HIV/AIDS by antibody gene transfer.

PubMed

Yang, Lili; Wang, Pin

2014-01-27

Despite tremendous efforts over the course of many years, the quest for an effective HIV vaccine by the classical method of active immunization remains largely elusive. However, two recent studies in mice and macaques have now demonstrated a new strategy designated as Vectored ImmunoProphylaxis (VIP), which involves passive immunization by viral vector-mediated delivery of genes encoding broadly neutralizing antibodies (bnAbs) for in vivo expression. Robust protection against virus infection was observed in preclinical settings when animals were given VIP to express monoclonal neutralizing antibodies. This unorthodox approach raises new promise for combating the ongoing global HIV pandemic. In this article, we survey the status of antibody gene transfer, review the revolutionary progress on isolation of extremely bnAbs, detail VIP experiments against HIV and its related virus conduced in humanized mice and macaque monkeys, and discuss the pros and cons of VIP and its opportunities and challenges towards clinical applications to control HIV/AIDS endemics.

Active immunity induced by passive IgG post-exposure protection against ricin.

PubMed

Hu, Charles Chen; Yin, Junfei; Chau, Damon; Cherwonogrodzky, John W; Hu, Wei-Gang

2014-01-21

Therapeutic antibodies can confer an instant protection against biothreat agents when administered. In this study, intact IgG and F(ab')2 from goat anti-ricin hyperimmune sera were compared for the protection against lethal ricin mediated intoxication. Similar ricin-binding affinities and neutralizing activities in vitro were observed between IgG and F(ab')2 when compared at the same molar concentration. In a murine ricin intoxication model, both IgG and F(ab')2 could rescue 100% of the mice by one dose (3 nmol) administration of antibodies 1 hour after 5 × LD50 ricin challenge. Nine days later, when the rescued mice received a second ricin challenge (5 × LD50), only the IgG-treated mice survived; the F(ab')2-treated mice did not. The experimental design excluded the possibility of residual goat IgG responsible for the protection against the second ricin challenge. Results confirmed that the active immunity against ricin in mice was induced quickly following the passive delivery of a single dose of goat IgG post-exposure. Furthermore, it was demonstrated that the induced active immunity against ricin in mice lasted at least 5 months. Therefore, passive IgG therapy not only provides immediate protection to the victim after ricin exposure, but also elicits an active immunity against ricin that subsequently results in long term protection.

Active Immunity Induced by Passive IgG Post-Exposure Protection against Ricin

PubMed Central

Hu, Charles Chen; Yin, Junfei; Chau, Damon; Cherwonogrodzky, John W.; Hu, Wei-Gang

2014-01-01

Therapeutic antibodies can confer an instant protection against biothreat agents when administered. In this study, intact IgG and F(ab’)2 from goat anti-ricin hyperimmune sera were compared for the protection against lethal ricin mediated intoxication. Similar ricin-binding affinities and neutralizing activities in vitro were observed between IgG and F(ab’)2 when compared at the same molar concentration. In a murine ricin intoxication model, both IgG and F(ab’)2 could rescue 100% of the mice by one dose (3 nmol) administration of antibodies 1 hour after 5 × LD50 ricin challenge. Nine days later, when the rescued mice received a second ricin challenge (5 × LD50), only the IgG-treated mice survived; the F(ab’)2-treated mice did not. The experimental design excluded the possibility of residual goat IgG responsible for the protection against the second ricin challenge. Results confirmed that the active immunity against ricin in mice was induced quickly following the passive delivery of a single dose of goat IgG post-exposure. Furthermore, it was demonstrated that the induced active immunity against ricin in mice lasted at least 5 months. Therefore, passive IgG therapy not only provides immediate protection to the victim after ricin exposure, but also elicits an active immunity against ricin that subsequently results in long term protection. PMID:24451844

Systemic antibodies administered by passive immunization prevent generalization of the infection by foot-and-mouth disease virus in cattle after oronasal challenge.

PubMed

Barrionuevo, Florencia; Di Giacomo, Sebastián; Bucafusco, Danilo; Ayude, Andrea; Schammas, Juan; Miraglia, M Cruz; Capozzo, Alejandra; Borca, Manuel V; Perez-Filgueira, Mariano

2018-05-01

The role of passively transferred sera in the protection against aerogenous foot-and-mouth disease (FMD) virus infection in cattle was evaluated using vaccine-induced immune serum preparations obtained at 7 and 26 days post-vaccination (dpv). We showed that circulating antibodies were sufficient to prevent disease generalization after oronasal infection in animals passively transferred with 26-dpv serum but not with the 7-dpv serum. Conversely, conventional FMD vaccination provided clinical protection at 7 dpv, promoting fast and robust antibody responses upon challenge and even though antibody titers were similar to those found in animals passively immunized with 7-dpv serum. These results demonstrate that presence of antigen-specific antibodies is critical to prevent the dissemination of the virus within the animal. Conventional FMD vaccination additionally promoted the deployment of rapid, high titer and isotype-switched antibody responses at systemic and mucosal levels after infection, thus conferring protection even in the presence of low pre-challenge antibody titers. Copyright © 2018 Elsevier Inc. All rights reserved.

Active Immunization with Pneumolysin versus 23-Valent Polysaccharide Vaccine for Streptococcus pneumoniae Keratitis

PubMed Central

Norcross, Erin W.; Sanders, Melissa E.; Moore, Quincy C.; Taylor, Sidney D.; Tullos, Nathan A.; Caston, Rhonda R.; Dixon, Sherrina N.; Nahm, Moon H.; Burton, Robert L.; Thompson, Hilary; McDaniel, Larry S.

2011-01-01

Purpose. The purpose of this study was to determine whether active immunization against pneumolysin (PLY), or polysaccharide capsule, protects against the corneal damage associated with Streptococcus pneumoniae keratitis. Methods. New Zealand White rabbits were actively immunized with Freund's adjuvant mixed with pneumolysin toxoid (ψPLY), Pneumovax 23 (PPSV23; Merck, Whitehouse Station, NJ), or phosphate-buffered saline (PBS), before corneal infection with 105 colony-forming units (CFU) of S. pneumoniae. Serotype-specific rabbit polyclonal antisera or mock antisera were passively administered to rabbits before either intravenous infection with 1011 CFU S. pneumoniae or corneal infection with 105 CFU of S. pneumoniae. Results. After active immunization, clinical scores of corneas of the rabbits immunized with ψPLY and Freund's adjuvant were significantly lower than scores of the rabbits that were mock immunized with PBS and Freund's adjuvant or with PPSV23 and Freund's adjuvant at 48 hours after infection (P ≤ 0.0010), whereas rabbits immunized with PPSV23 and Freund's adjuvant failed to show differences in clinical scores compared with those in mock-immunized rabbits (P = 1.00) at 24 and 48 hours after infection. Antisera from rabbits actively immunized with PPSV23 and Freund's adjuvant were nonopsonizing. Bacterial loads recovered from infected corneas were higher for the ψPLY- and PPSV23-immunized rabbits after infection with WU2, when compared with the mock-immunized rabbits (P ≤ 0.007). Conversely, after infection with K1443, the ψPLY-immunized rabbits had lower bacterial loads than the control rabbits (P = 0.0008). Quantitation of IgG, IgA, and IgM in the sera of ψPLY-immunized rabbits showed high concentrations of PLY-specific IgG. Furthermore, anti-PLY IgG purified from ψPLY-immunized rabbits neutralized the cytolytic effects of PLY on human corneal epithelial cells. Passive administration of serotype-specific antisera capable of opsonizing and killing S. pneumoniae protected against pneumococcal bacteremia (P ≤ 0.05), but not against keratitis (P ≥ 0.476). Conclusions. Active immunization with pneumococcal capsular polysaccharide and Freund's adjuvant fails to produce opsonizing antibodies, and passive administration of serotype specific opsonizing antibodies offers no protection against pneumococcal keratitis in the rabbit, whereas active immunization with the conserved protein virulence factor PLY and Freund's adjuvant is able to reduce corneal inflammation associated with pneumococcal keratitis, but has variable effects on bacterial loads in the cornea. PMID:22039231

Acquisition of Maternal Antibodies both from the Placenta and by Lactation Protects Mouse Offspring from Yersinia pestis Challenge

PubMed Central

Qi, Zhizhen; Zhao, Haihong; Zhang, Qingwen; Bi, Yujing; Ren, Lingling; Zhang, Xuecan; Yang, Hanqing; Yang, Xiaoyan; Wang, Qiong; Li, Cunxiang; Zhou, Jiyuan; Xin, Youquan; Yang, Yonghai; Yang, Huiying; Du, Zongmin; Tan, Yafang; Han, Yanping; Song, Yajun; Zhou, Lei; Zhang, Pingping; Cui, Yujun; Yan, Yanfeng; Zhou, Dongsheng

2012-01-01

Artificially passive immunization has been demonstrated to be effective against Yersinia pestis infection in animals. However, maternal antibodies' protective efficacy against plague has not yet been demonstrated. Here, we evaluated the kinetics, protective efficacy, and transmission modes of maternal antibodies, using mice immunized with plague subunit vaccine SV1 (20 μg of F1 and 10 μg of rV270). The results showed that the rV270- and F1-specific antibodies could be detected in the sera of newborn mice (NM) until 10 and 14 weeks of age, respectively. There was no antibody titer difference between the parturient mice immunized with SV1 (PM-S) and the caesarean-section newborns (CSN) from the PM-S or between the lactating mice immunized by SV1 (LM-S) and the cross-fostered mice (CFM) during 3 weeks of lactation. The NM had a 72% protection against 4,800 CFU Y. pestis strain 141 challenge at 6 weeks of age, whereas at 14 weeks of age, NM all succumbed to 5,700 CFU of Y. pestis challenge. After 7 weeks of age, CFM had an 84% protection against 5,000 CFU of Y. pestis challenge. These results indicated that maternal antibodies induced by the plague subunit vaccine in mother mice can be transferred to NM by both placenta and lactation. Passive antibodies from the immunized mothers could persist for 3 months and provide early protection for NM. The degree of early protection is dependent on levels of the passively acquired antibody. The results indicate that passive immunization should be an effective countermeasure against plague during its epidemics. PMID:22933398

Anti-Aß immunotherapy in Alzheimer's disease; relevance of transgenic mouse studies to clinical trials

PubMed Central

Wilcock, Donna M.; Colton, Carol A.

2009-01-01

Therapeutic approaches to the treatment of Alzheimer's disease are focused primarily on the Aß peptide which aggregates to form amyloid deposits in the brain. The amyloid hypothesis states that amyloid is the precipitating factor that results in the other pathologies of Alzheimer's, namely neurofibrillary tangles and neurodegeneration, as well as the clinical dementia. One such therapy that has attracted significant attention is anti-Aß immunotherapy. First described in 1999, immunotherapy uses anti-Aß antibodies to lower brain amyloid levels. Active immunization, in which Aß is combined with an adjuvant to stimulate an immune response producing antibodies and passive immunization, in which antibodies are directly injected, were shown to lower brain amyloid levels and improve cognition in multiple transgenic mouse models. Mechanisms of action were studied in these mice and revealed a complex set of mechanisms that depended on the type of antibody used. When active immunization advanced to clinical trials a subset of patients developed meningoencephalitis; an event not predicted in mouse studies. However, it was suspected that a T-cell response due to the type of adjuvant used was the cause of the meningoencephalitis and studies in mice indicated alternative methods of vaccination. Passive immunization has also advanced to phase III clinical trials on the basis of successful transgenic mouse studies. Reports from the active immunization clinical trial indicated that, indeed, amyloid levels in brain were reduced. While APP transgenic mouse models are useful in studying amyloid pathology these mice do not generate significant tau pathology or neuron loss. Continued development of new mouse models that do generate all of these pathologies will be critical in more accurately testing therapeutics and predicting the clinical outcome of such therapeutics. PMID:19096156

Mice are actively immunized after passive monoclonal antibody prophylaxis and ricin toxin challenge. (Reannouncement with new availability information)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lemley, P.V.; Wright, D.C.

1992-12-31

Mice passively immunized by a protective, anti-ricin A-chain monoclonal antibody, then challenged intravenously with ricin, were protected from a subsequent ricin challenge, and were actively immunized. Two significant advantages accrued from this experiment: the monoclonal antibody neutralized the toxicity of the ricin immunogen, and active immunization was achieved with very low antigen load (approx. 0.5 micrograms/mouse). We ruled out the possibility that residual monoclonal antibody provided the protection by using three independent criteria. There was significant (four orders of magnitude) enhancement of the immune response in the presence of the monoclonal antibody; control immunizations of mice with ricin A-chain, ricinmore » B-chain or either chain with the monoclonal antibody did not induce active immunity; and the active immunization could not be replicated when protective goat polyclonal antibody was substituted for the monoclonal antibody. Because high titers were achieved rapidly without any adjuvant, we are currently investigating haptenized ricin to determine if anti-hapten monoclonal antibodies can be produced by this refined procedure.« less

The multi-faceted role of allergen exposure to the local airway mucosa.

PubMed

Golebski, K; Röschmann, K I L; Toppila-Salmi, S; Hammad, H; Lambrecht, B N; Renkonen, R; Fokkens, W J; van Drunen, C M

2013-02-01

Airway epithelial cells are the first to encounter aeroallergens and therefore have recently become an interesting target of many studies investigating their involvement in the modulation of allergic inflammatory responses. Disruption of a passive structural barrier composed of epithelial cells by intrinsic proteolytic activity of allergens may facilitate allergen penetration into local tissues and additionally affect chronic and ongoing inflammatory processes in respiratory tissues. Furthermore, the ability of rhinoviruses to disrupt and interfere with epithelial tight junctions may alter the barrier integrity and enable a passive passage of inhaled allergens through the airway epithelium. On the other hand, epithelial cells are no longer considered to act only as a physical barrier toward inhaled allergens, but also to actively contribute to airway inflammation by detecting and responding to environmental factors. Epithelial cells can produce mediators, which may affect the recruitment and activation of more specialized immune cells to the local tissue and also create a microenvironment in which these activated immune cells may function and propagate the inflammatory processes. This review presents the dual role of epithelium acting as a passive and active barrier when encountering an inhaled allergen and how this double role contributes to the start of local immune responses. © 2012 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

Maternal Milk T Cells Drive Development of Transgenerational Th1 Immunity in Offspring Thymus.

PubMed

Ghosh, Mrinal K; Nguyen, Virginia; Muller, H Konrad; Walker, Ameae M

2016-09-15

Using multiple murine foster-nursing protocols, thereby eliminating placental transfer and allowing a distinction between dam- and pup-derived cells, we show that foster nursing by an immunized dam results in development of CD8(+) T cells in nonimmunized foster pups that are specific for Ags against which the foster dam was immunized (Mycobacterium tuberculosis or Candida albicans). We have dubbed this process "maternal educational immunity" to distinguish it from passive cellular immunity. Of the variety of maternal immune cells present in milk, only T cells were detected in pup tissues. Maternal T cells, a substantial percentage of which were CD4(+)MHC class II(+), accumulated in the pup thymus and spleen during the nursing period. Further analysis of maternal cells in the pup thymus showed that a proportion was positive for maternal immunogen-specific MHC class II tetramers. To determine the outcome of Ag presentation in the thymus, the maternal or foster pup origin of immunogen-responding CD8(+) cells in foster pup spleens was assessed. Whereas ∼10% were maternally derived in the first few weeks after weaning, all immunogen-responding CD8(+) T cells were pup derived by 12 wk of age. Pup-derived immunogen-responsive CD8(+) cells persisted until at least 1 y of age. Passive cellular immunity is well accepted and has been demonstrated in the human population. In this study, we show an arguably more important role for transferred immune cells: the direction of offspring T cell development. Harnessing maternal educational immunity through prepregnancy immunization programs has potential for improvement of infant immunity. Copyright © 2016 by The American Association of Immunologists, Inc.

Defense from the Group A Streptococcus by active and passive vaccination with the streptococcal hemoprotein receptor.

PubMed

Huang, Ya-Shu; Fisher, Morly; Nasrawi, Ziyad; Eichenbaum, Zehava

2011-06-01

The worldwide burden of the Group A Streptococcus (GAS) primary infection and sequelae is considerable, although immunization programs with broad coverage of the hyper variable GAS are still missing. We evaluate the streptococcal hemoprotein receptor (Shr), a conserved streptococcal protein, as a vaccine candidate against GAS infection. Mice were immunized intraperitoneally with purified Shr or intranasally with Shr-expressing Lactococcus lactis. The resulting humoral response in serum and secretions was determined. We evaluated protection from GAS infection in mice after active or passive vaccination with Shr, and Shr antiserum was tested for bactericidal activity. A robust Shr-specific immunoglobulin (Ig) G response was observed in mouse serum after intraperitoneal vaccination with Shr. Intranasal immunization elicited both a strong IgG reaction in the serum and a specific IgA reaction in secretions. Shr immunization in both models allowed enhanced protection from systemic GAS challenge. Rabbit Shr antiserum was opsonizing, and mice that were administrated with Shr antiserum prior to the infection demonstrated a significantly higher survival rate than did mice treated with normal rabbit serum. Shr is a promising vaccine candidate that is capable of eliciting bactericidal antibody response and conferring immunity against systemic GAS infection in both passive and active vaccination models.

Systemic bacterial infection and immune defense phenotypes in Drosophila melanogaster.

PubMed

Khalil, Sarah; Jacobson, Eliana; Chambers, Moria C; Lazzaro, Brian P

2015-05-13

The fruit fly Drosophila melanogaster is one of the premier model organisms for studying the function and evolution of immune defense. Many aspects of innate immunity are conserved between insects and mammals, and since Drosophila can readily be genetically and experimentally manipulated, they are powerful for studying immune system function and the physiological consequences of disease. The procedure demonstrated here allows infection of flies by introduction of bacteria directly into the body cavity, bypassing epithelial barriers and more passive forms of defense and allowing focus on systemic infection. The procedure includes protocols for the measuring rates of host mortality, systemic pathogen load, and degree of induction of the host immune system. This infection procedure is inexpensive, robust and quantitatively repeatable, and can be used in studies of functional genetics, evolutionary life history, and physiology.

Can Alzheimer disease be prevented by amyloid-β immunotherapy?

PubMed Central

Lemere, Cynthia A.; Masliah, Eliezer

2010-01-01

Alzheimer disease (AD) is the most common form of dementia. The amyloid-β (Aβ) peptide has become a major therapeutic target in AD on the basis of pathological, biochemical and genetic evidence that supports a role for this molecule in the disease process. Active and passive Aβ immunotherapies have been shown to lower cerebral Aβ levels and improve cognition in animal models of AD. In humans, dosing in the phase II clinical trial of the AN1792 Aβ vaccine was stopped when ~6% of the immunized patients developed meningoencephalitis. However, some plaque clearance and modest clinical improvements were observed in patients following immunization. As a result of this study, at least seven passive Aβ immunotherapies are now in clinical trials in patients with mild to moderate AD. Several second-generation active Aβ vaccines are also in early clinical trials. On the basis of preclinical studies and the limited data from clinical trials, Aβ immunotherapy might be most effective in preventing or slowing the progression of AD when patients are immunized before or in the very earliest stages of disease onset. Biomarkers for AD and imaging technology have improved greatly over the past 10 years and, in the future, might be used to identify presymptomatic, at-risk individuals who might benefit from Aβ immunization. PMID:20140000

Study on passive immunity: Time of vaccination in kids born to goats vaccinated against Peste des petits ruminants.

PubMed

Balamurugan, Vinayagamurthy; Sen, Arnab; Venkatesan, Gnanavel; Rajak, Kaushal Kishor; Bhanuprakash, Veerakyathappa; Singh, Raj Kumar

2012-08-01

In this study, the decay of maternal peste des petits ruminants virus (PPRV) antibodies in kids born to goats vaccinated with Asian lineage IV PPR vaccine and the efficacy of passive immunity against PPRV was assessed to determine the appropriate period for vaccination in kids. Serum samples collected from kids born to vaccinated, unvaccinated and infected goats at different time intervals were tested by PPR competitive ELISA and serum neutralization test (SNT). Maternal antibodies in kids were detectable up to 6 months with a decline trend from the third month onwards and receded below the protective level by the fourth month. The kid with an SN titre of 1:8 at the time of immunization showed significant PPRV specific antibody response (percentage inhibition of 76; SN titers >1:16), when tested on 21 day post-vaccination and was completely protected from infection upon virulent PPRV challenge. Similarly, the kid with 1:8 SN titers was completely protected from PPR infection on active challenge. Therefore, PPR vaccination is recommended in kids, aged 4 months and born to immunized or exposed goats. This could be a suitable period to avoid window of susceptibility in kids to PPRV and the effort to eliminate PPR infection from susceptible populations.

Passive Immunization with Anti-Tau Antibodies in Two Transgenic Models

PubMed Central

Chai, Xiyun; Wu, Su; Murray, Tracey K.; Kinley, Robert; Cella, Claire V.; Sims, Helen; Buckner, Nicola; Hanmer, Jenna; Davies, Peter; O'Neill, Michael J.; Hutton, Michael L.; Citron, Martin

2011-01-01

The microtubule-associated protein Tau plays a critical role in the pathogenesis of Alzheimer disease and several related disorders (tauopathies). In the disease Tau aggregates and becomes hyperphosphorylated forming paired helical and straight filaments, which can further condense into higher order neurofibrillary tangles in neurons. The development of this pathology is consistently associated with progressive neuronal loss and cognitive decline. The identification of tractable therapeutic targets in this pathway has been challenging, and consequently very few clinical studies addressing Tau pathology are underway. Recent active immunization studies have raised the possibility of modulating Tau pathology by activating the immune system. Here we report for the first time on passive immunotherapy for Tau in two well established transgenic models of Tau pathogenesis. We show that peripheral administration of two antibodies against pathological Tau forms significantly reduces biochemical Tau pathology in the JNPL3 mouse model. We further demonstrate that peripheral administration of the same antibodies in the more rapidly progressive P301S tauopathy model not only reduces Tau pathology quantitated by biochemical assays and immunohistochemistry, but also significantly delays the onset of motor function decline and weight loss. This is accompanied by a reduction in neurospheroids, providing direct evidence of reduced neurodegeneration. Thus, passive immunotherapy is effective at preventing the buildup of intracellular Tau pathology, neurospheroids, and associated symptoms, although the exact mechanism remains uncertain. Tau immunotherapy should therefore be considered as a therapeutic approach for the treatment of Alzheimer disease and other tauopathies. PMID:21841002

Oral rice-based vaccine induces passive and active immunity against enterotoxigenic E. coli-mediated diarrhea in pigs.

PubMed

Takeyama, Natsumi; Yuki, Yoshikazu; Tokuhara, Daisuke; Oroku, Kazuki; Mejima, Mio; Kurokawa, Shiho; Kuroda, Masaharu; Kodama, Toshiaki; Nagai, Shinya; Ueda, Susumu; Kiyono, Hiroshi

2015-09-22

Enterotoxigenic Escherichia coli (ETEC) causes severe diarrhea in both neonatal and weaned pigs. Because the cholera toxin B subunit (CTB) has a high level of amino acid identity to the ETEC heat-labile toxin (LT) B-subunit (LTB), we selected MucoRice-CTB as a vaccine candidate against ETEC-induced pig diarrhea. When pregnant sows were orally immunized with MucoRice-CTB, increased amounts of antigen-specific IgG and IgA were produced in their sera. CTB-specific IgG was secreted in the colostrum and transferred passively to the sera of suckling piglets. IgA antibodies in the colostrum and milk remained high with a booster dose after farrowing. Additionally, when weaned minipigs were orally immunized with MucoRice-CTB, production of CTB-specific intestinal SIgA, as well as systemic IgG and IgA, was induced. To evaluate the cross-protective effect of MucoRice-CTB against ETEC diarrhea, intestinal loop assay with ETEC was conducted. The fluid volume accumulated in the loops of minipigs immunized with MucoRice-CTB was significantly lower than that in control minipigs, indicating that MucoRice-CTB-induced cross-reactive immunity could protect weaned pigs from diarrhea caused by ETEC. MucoRice-CTB could be a candidate oral vaccine for inducing both passive and active immunity to protect both suckling and weaned piglets from ETEC diarrhea. Copyright © 2015 Elsevier Ltd. All rights reserved.

[Immunotherapies for drug addictions].

PubMed

Montoya, Ivan

2008-01-01

Immunotherapies in the form of vaccines (active immunization) or monoclonal antibodies (passive immunization) appear safe and a promising treatment approaches for some substance-related disorders. The mechanism of action of the antibody therapy is by preventing the rapid entry of drugs of abuse into the central nervous system. In theory, immunotherapies could have several clinical applications. Monoclonal antibodies may be useful to treat drug overdoses and prevent the neurotoxic effects of drugs by blocking the access of drugs to the brain. Vaccines may help to prevent the development of addiction, initiate drug abstinence in those already addicted to drugs, or prevent drug use relapse by reducing the pharmacological effects and rewarding properties of the drugs of abuse on the brain. Passive immunization with monoclonal antibodies has been investigated for cocaine, methamphetamine, nicotine, and phencyclidine (PCP). Active immunization with vaccines has been studied for cocaine, heroin, methamphetamine, and nicotine. These immunotherapies seem promising therapeutic tools and are at different stages in their development before they can be approved by regulatory agencies for the treatment of substance-related disorders. The purpose of this article is to review the current immunotherapy approaches with emphasis on the risks and benefits for the treatment of these disorders.

Immune-Based Approaches to the Prevention of Mother-to-child-Transmission of HIV-1: Active and Passive Immunization

PubMed Central

Lohman-Payne, Barb; Slyker, Jennifer; Rowland-Jones, Sarah L.

2010-01-01

Synopsis Despite more than two decades of research, an effective vaccine that can prevent HIV-1 infection in populations exposed to the virus remains elusive. In the pursuit of an HIV-1 vaccine, does prevention of exposure to maternal HIV-1 in utero, at birth or in early life through breast-milk require special consideration? In this article we will review what is known about the immune mechanisms of susceptibility and resistance to mother-to-child transmission (MTCT) of HIV-1 and will summarise studies that have used passive or active immunisation strategies to interrupt -MTCT of HIV-1. We will also describe potentially modifiable infectious co-factors that may enhance transmission and/or disease progression (especially in the developing world). Ultimately an effective prophylactic vaccine against HIV-1 infection will need to be deployed as part of the Extended Programme of Immunisation (EPI) recommended by the World Health Organisation (WHO) for use in developing countries, so it is important to understand how the infant immune system responds to HIV-1 antigens, both in natural infection and presented by candidate vaccines. PMID:21078451

Inmunoterapias para las adicciones a las drogas Immunotherapies for Drug Addictions

PubMed Central

Montoya, Iván D.

2008-01-01

Immunotherapies in the form of vaccines (active immunization) or monoclonal antibodies (passive immunization) appear safe and a promising treatment approaches for some substance-related disorders. The mechanism of action of the antibody therapy is by preventing the rapid entry of drugs of abuse into the central nervous system. In theory, immunotherapies could have several clinical applications. Monoclonal antibodies may be useful to treat drug overdoses and prevent the neurotoxic effects of drugs by blocking the access of drugs to the brain. Vaccines may help to prevent the development of addiction, initiate drug abstinence in those already addicted to drugs, or prevent drug use relapse by reducing the pharmacological effects and rewarding properties of the drugs of abuse on the brain. Passive immunization with monoclonal antibodies has been investigated for cocaine, methamphetamine, nicotine, and phencyclidine (PCP). Active immunization with vaccines has been studied for cocaine, heroin, methamphetamine, and nicotine. These immunotherapies seem promising therapeutic tools and are at different stages in their development before they can be approved by regulatory agencies for the treatment of substance-related disorders. The purpose of this article is to review the current immunotherapy approaches with emphasis on the risks and benefits for the treatment of these disorders. PMID:18551223

Establishing a small animal model for evaluating protective immunity against mumps virus.

PubMed

Pickar, Adrian; Xu, Pei; Elson, Andrew; Zengel, James; Sauder, Christian; Rubin, Steve; He, Biao

2017-01-01

Although mumps vaccines have been used for several decades, protective immune correlates have not been defined. Recently, mumps outbreaks have occurred in vaccinated populations. To better understand the causes of the outbreaks and to develop means to control outbreaks in mumps vaccine immunized populations, defining protective immune correlates will be critical. Unfortunately, no small animal model for assessing mumps immunity exists. In this study, we evaluated use of type I interferon (IFN) alpha/beta receptor knockout mice (IFN-α/βR-/-) for such a model. We found these mice to be susceptible to mumps virus administered intranasally and intracranially. Passive transfer of purified IgG from immunized mice protected naïve mice from mumps virus infection, confirming the role of antibody in protection and demonstrating the potential for this model to evaluate mumps immunity.

Guidelines for pre-clinical assessment of the acetylcholine receptor-specific passive transfer myasthenia gravis model - recommendations for methods and experimental designs

PubMed Central

Kusner, Linda L.; Losen, Mario; Vincent, Angela; Lindstrom, Jon; Tzartos, Socrates; Lazaridis, Konstantinos; Martinez-Martinez, Pilar

2015-01-01

Antibodies against the muscle acetylcholine receptor (AChR) are the most common cause of myasthenia gravis (MG). Passive transfer of AChR antibodies from MG patients into animals reproduces key features of human disease, including antigenic modulation of the AChR, complement-mediated damage of the neuromuscular junction, and muscle weakness. Similarly, AChR antibodies generated by active immunization in experimental autoimmune MG models can subsequently be passively transferred to other animals and induce weakness. The passive transfer model is useful to test therapeutic strategies aimed at the effector mechanism of the autoantibodies. Here we summarize published and unpublished experience using the AChR passive transfer MG model in mice, rats and rhesus monkeys, and give recommendations for the design of preclinical studies in order to facilitate translation of positive and negative results to improve MG therapies. PMID:25743217

Enterovirus 71 can directly infect the brainstem via cranial nerves and infection can be ameliorated by passive immunization.

PubMed

Tan, Soon Hao; Ong, Kien Chai; Wong, Kum Thong

2014-11-01

Enterovirus 71 (EV71)-associated hand, foot, and mouth disease may be complicated by encephalomyelitis. We investigated EV71 brainstem infection and whether this infection could be ameliorated by passive immunization in a mouse model. Enterovirus 71 was injected into unilateral jaw/facial muscles of 2-week-old mice, and hyperimmune sera were given before or after infection. Harvested tissues were studied by light microscopy, immunohistochemistry, in situ hybridization, and viral titration. In unimmunized mice, viral antigen and RNA were detected within 24 hours after infection only in ipsilateral cranial nerves, motor trigeminal nucleus, reticular formation, and facial nucleus; viral titers were significantly higher in the brainstem than in the spinal cord samples. Mice given preinfection hyperimmune serum showed a marked reduction of ipsilateral viral antigen/RNA and viral titers in the brainstem in a dose-dependent manner. With optimum hyperimmune serum given after infection, brainstem infection was significantly reduced in a time-dependent manner. A delay in disease onset and a reduction of disease severity and mortality were also observed. Thus, EV71 can directly infect the brainstem, including the medulla, via cranial nerves, most likely by retrograde axonal transport. This may explain the sudden cardiorespiratory collapse in human patients with fatal encephalomyelitis. Moreover, our results suggest that passive immunization may still benefit EV71-infected patients who have neurologic complications.

The duration of passive protection against Taenia ovis larvae in lambs.

PubMed

Heath, D D; Yong, W K; Osborn, P J; Parmeter, S N; Lawrence, S B; Twaalfhoven, H

1979-10-01

In an attempt to induce passive protection in lambs against Taenia ovis larvae that would last for the 15-20 weeks from birth to slaughter as fat lambs, one group of ewes was immunized by a series of injections of 2000, 4000, 8000, 16 000 and 32 000 activated oncospheres of Taenia ovis prior to parturition. Another group of ewes was not immunized. All ewes had previously grazed pasture lightly infected with T. ovis eggs. Most lambs from non-immunized ewes developed cysts after oral infection with T. ovis eggs. However, no lambs from immunized ewes developed cysts up to and including 6 weeks after birth. Between 8 and 16 weeks after birth a proportion of lambs were found to be susceptible to infection. By 18 weeks after birth all lambs were apparently susceptible. The 99% confidence band for the mean duration of demonstrable complement-fixing antibody titres was 6.2-7.8 weeks for lambs from immunized ewes. The persistence of maternal protective antibody in some lambs could possibly preclude successful active immunization of all lambs against T. ovis larvae before 18 weeks of age.

[The use of passive rabies immunotherapy: from the past to the future].

PubMed

Bourhy, Hervé; Dacheux, Laurent; Ribadeau-Dumas, Florence

2010-01-01

Rabies is a fatal disease transmitted by infected animals by bite, scratch, licking on broken skin or contamination of mucosis by saliva. The regimen of post-exposure prophylaxis for people not previously vaccinated, that is currently recommended by WHO, consists of a combination of wound cleaning, active immunization and passive immunization when the exposure is of category 3. Most of the products available on the market, in particular human rabies immunoglobulins, highly purified equine rabies immunoglobulins and the derived F(ab')(2) fragments, are now characterized by high potency and safety. Although the interest of passive anti-rabies immunization was first demonstrated in the first half of the 20th century, there is still an inadequate supply of these products to the target populations mostly in developing countries. Therefore, it is urgent to set-up training and information actions for healthcare personnel on the need to use passive immunotherapy and the lack of adverse effects of the related products. For the future, we hope that a scale up of production and a lower price will improve the accessibility to these products. The development of new products based on monoclonal antibodies and molecular biology, and which may be cheaper, is promising. © Société de Biologie, 2010.

The impact of maternal measles-rubella immunization on the 12-month-old infant's immune response to measles-mumps-rubella vaccine immunogenicity.

PubMed

Saffar, M-J; Ajami, A; Khalilian, A-R; Saffar, H

2009-07-01

This study was conducted to assess the roles of maternal measles-rubella (MR) vaccination before pregnancy on the persistence of passive immunity against MR in their infant before measles-mumps-rubella (MMR) immunization and the effects on the immunogenicity of MMR vaccine. Before and 4-8 weeks after MMR immunization of all healthy 12-month-old infants, sera samples were prepared. According to their mother's history of MR vaccination, infants were divided into two groups. Anti-MR antibodies were measured by the quantitative enzyme-linked immunosorbent assay (ELISA) method. The difference in seroconversion rates and the mean concentration of antibodies (MCA) between the two groups of infants were analyzed by descriptive statistical methods. In total, 7 and 12 sera, all from infants born from MR-vaccinated mothers, were positive against measles and rubella, respectively. The seroconversion rates were 90.5 and 53% in seronegative infants against measles and rubella, respectively, without statistically significant differences between the two groups of infants. However, the MCA differences were significant; measles P = 0.000, rubella P = 0.019. The MR vaccination of mothers may cause the prolongation of passive immunity in their infants, and may influence the immunogenicity of MMR vaccination. This finding should be considered for the optimal scheduling of the first dose of MMR vaccine. Also, the results showed that the immunogenicity of the rubella component of the MMR vaccine was lower than that reported.

Guinea pigs inbred for studies of respiratory anaphylaxis.

PubMed

Lundberg, L

1979-02-01

A selective inbreeding of approximately 24 generations of albino guinea pigs by brother x sister mating has resulted in two strains, registered IMM/S and IMM/R, with high and low responsiveness, respectively, to ovalbumin-induced respiratory anaphylaxis. The two guinea pig strains differed in their ability to be immunized by the inhalation of antigen and produce antibodies, as well as to develop respiratory anaphylaxis. A correlation between the strength of the anaphylactic reactions and the amount of hemagglutinating antibodies produced was observed. When immunization was carried out by an intradermal injection of ovalbumin (OA), even in small doses incorporated in FCA, guinea pigs from both strains produced hemagglutinating antibodies in nearly the same amount. These antibodies do not influence the ability of the animals to react with a high respectively low anaphylactic response on subsequent challenge by inhalation of OA, neither in the actively sensitized animals nor in passively sensitized animals. However, with repeated inhalations of OA, desensitization occurred in the intradermally immunized high-responders, while the passively immunized high-responders could be provoked several times without any signs of desensitization. No systematical differences between the two strains with regard to sensitivity to inhalations of histamine were demonstrated. The low responders were found to be less resistant to infections than high-responders.

The genomic features of parasitism, Polyembryony and immune evasion in the endoparasitic wasp Macrocentrus cingulum.

PubMed

Yin, Chuanlin; Li, Meizhen; Hu, Jian; Lang, Kun; Chen, Qiming; Liu, Jinding; Guo, Dianhao; He, Kang; Dong, Yipei; Luo, Jiapeng; Song, Zhenkun; Walters, James R; Zhang, Wenqing; Li, Fei; Chen, Xuexin

2018-05-30

Parasitoid wasps are well-known natural enemies of major agricultural pests and arthropod borne diseases. The parasitoid wasp Macrocentrus cingulum (Hymenoptera: Braconidae) has been widely used to control the notorious insect pests Ostrinia furnacalis (Asian Corn Borer) and O. nubilalis (European corn borer). One striking phenomenon exhibited by M. cingulum is polyembryony, the formation of multiple genetically identical offspring from a single zygote. Moreover, M. cingulum employs a passive parasitic strategy by preventing the host's immune system from recognizing the embryo as a foreign body. Thus, the embryos evade the host's immune system and are not encapsulated by host hemocytes. Unfortunately, the mechanism of both polyembryony and immune evasion remains largely unknown. We report the genome of the parasitoid wasp M. cingulum. Comparative genomics analysis of M. cingulum and other 11 insects were conducted, finding some gene families with apparent expansion or contraction which might be linked to the parasitic behaviors or polyembryony of M. cingulum. Moreover, we present the evidence that the microRNA miR-14b regulates the polyembryonic development of M. cingulum by targeting the c-Myc Promoter-binding Protein 1 (MBP-1), histone-lysine N-methyltransferase 2E (KMT2E) and segmentation protein Runt. In addition, Hemomucin, an O-glycosylated transmembrane protein, protects the endoparasitoid wasp larvae from being encapsulated by host hemocytes. Motif and domain analysis showed that only the hemomucin in two endoparasitoids, M. cingulum and Venturia canescens, possessing the ability of passive immune evasion has intact mucin domain and similar O-glycosylation patterns, indicating that the hemomucin is a key factor modulating the immune evasion. The microRNA miR-14b participates in the regulation of polyembryonic development, and the O-glycosylation of the mucin domain in the hemomucin confers the passive immune evasion in this wasp. These key findings provide new insights into the polyembryony and immune evasion.

Operational Efficiency of an Immunization Clinic Attached to Rural Health Training Centre in Delhi, India: A Time and Motion Study

PubMed Central

Kumar, Varun; Mangal, Abha; Panesar, Sanjeet; Yadav, Geeta; Talwar, Richa; Raut, Deepak; Singh, Saudan

2014-01-01

Background. Obtaining baseline data about current patterns of work is important for assessing the effects of interventions designed to improve care delivery. Time and motion studies allow for the most accurate measurement of structured components. Therefore, the present study was conducted to study the operational efficiency of an immunization clinic in Delhi, India. Methods. An observational cross-sectional study was conducted at the immunization clinic of Rural Health Training Centre in Delhi, India, from January 2014 to March 2014. The study composed two stage evaluations, a passive observation and a time and motion study. Systemic random sampling method was used to select 863 mothers/caregivers attending the immunization clinic. Results. At the immunization clinic, the study participants spent 64.1% of their total time in waiting. For new cases, the mean time taken for initial registration and receiving postvaccination advice was found to be significantly longer than old cases. Delivering health care services took more time during Mondays and also during the first hour of the day. Conclusion. Results of this study will guide public health decision-makers at all government levels in planning and implementation of immunization programs in developing countries. PMID:25431679

Production of monoclonal antibody inhibiting dipeptidylaminopeptidase IV activity of Porphyromonas gingivalis.

PubMed

Teshirogi, K; Hayakawa, M; Ikemi, T; Abiko, Y

2003-06-01

Porphyromonas gingivalis is a Gram-negative anaerobic bacterial species implicated as an important pathogen in the development of adult periodontitis. We previously cloned a gene encoding dipeptydilaminopeptidase IV (DAPIV) from P. gingivalis. In the present study, for immunological diagnosis and development of passive immunization, we produced a mouse monoclonal antibody (MAb) capable of inhibiting the DAPIV activity of P. gingivalis using highly purified recombinant DAPIV as an immunogen. The constructed MAb, designated as MAb-Pg-DAP-1, significantly inhibited DAPIV activity in P. gingivalis, as well as slightly inhibited that in other gram-negative bacteria such as Porphyromonas endodontalis and Prevotella loesheii, whereas no inhibition was seen in the gram-positive bacteria Streptococcus mutans and Actinomyces viscosus. Furthermore, the MAb did not inhibit DAPIV enzyme activity in human serum. This novel MAb may be useful for the development of immunological diagnosis capability and in passive immunization.

Antigen size and charge in immune complex glomerulonephritis. II. Passive induction of immune deposits with dextran-anti-dextran immune complexes.

PubMed Central

Isaacs, K. L.; Miller, F.

1983-01-01

Utilizing dextrans of restricted sizes (10,000, 70,000, 500,000 daltons), modified with regard to charge (neutral, polycationic, polyanionic) and an anti-dextran murine IgA myeloma, W3129, the authors have examined a model that may be used in the study of the combined effect of size and charge on renal deposition of immune complexes. Polycationic DEAE dextran complexes, using the 10,000 dalton antigen, showed a mesangiocapillary pattern of deposition. The other antigens showed focal to diffuse mesangial localization of varying degree. This indicates the potential usefulness of this system in examining the factors important in glomerular immune injury. The relevance to other observations, importance of polysaccharide antigens, and role in circulating versus in situ or "planted" immune complex models are considered. Images Figure 3 Figure 4 Figure 5 Figure 6 PMID:6190406

Comparative study of two human diploid rabies vaccines administered with antirabies globulin.

PubMed

Vodopija, I; Sureau, P; Smerdel, S; Lafon, M; Baklaic, Z; Ljubicic, M; Svjetlicic, M

1988-12-01

The association of human rabies immune globulin (HRIG) to the vaccine is recommended for postexposure rabies treatment in cases of severe exposure. In a previous study using an abbreviated postexposure vaccination schedule it was observed that passive immunization could partially inhibit the active immune response, with three cell-culture purified vaccines but not with the concentrated human diploid cell vaccine (HDCV). In order to see if this difference was related to the purification process, the present study was designed comparing two HDCV, one concentrated and the other concentrated and purified, both of them administered in association with HRIG. The neutralizing antibody response in the vaccines was found to be identical with both vaccines, ruling out the role of the purification and confirming the excellent immunogenicity of both human diploid cell vaccines and the absence of inhibition of the active immune response by the association of HRIG to HDCV.

Safety and Immunogenicity of a Mycoplasma ovipneumoniae bacterin for domestic sheep (Ovis aries).

PubMed

Ziegler, Jessie C; Lahmers, Kevin K; Barrington, George M; Parish, Steven M; Kilzer, Katherine; Baker, Katherine; Besser, Thomas E

2014-01-01

Mortality from epizootic pneumonia is hindering re-establishment of bighorn sheep populations in western North America. Mycoplasma ovipneumoniae, a primary agent of this disease, is frequently carried asymptomatically by the domestic sheep and goats that constitute the reservoir of this agent for transmission to bighorn sheep. Our long-term objective is to reduce the risk of M. ovipneumoniae infection of bighorn sheep; one approach to this objective is to control the pathogen in its reservoir hosts. The safety and immunogenicity of M. ovipneumoniae for domestic sheep was evaluated in three experimental immunization protocols: 1) live M. ovipneumoniae (50 ug protein); 2) killed M. ovipneumoniae (50 ug whole cell protein) in oil adjuvant; and 3) killed M. ovipneumoniae (250 ug whole cell protein) in oil adjuvant. Immunogenicity was assessed by two serum antibody measures: competitive enzyme-linked immunosorbent assay (cELISA) (experiments 1-3) and serum growth inhibition (Experiment 3). Passive immunogenicity was also assessed in the third experiment using the same assays applied to blood samples obtained from the lambs of immunized ewes. Adverse reactions to immunization were generally minor, but local reactions were regularly observed at immunization sites with bacterins in oil adjuvants. No evidence of M. ovipneumoniae specific antibody responses were observed in the first or second experiments and no resistance to colonization was observed in the first experiment. However, the ewes in the third experiment developed strong cELISA serum antibody responses and significant serum M. ovipneumoniae inhibition activity, and these responses were passively transferred to their lambs. The results of these trials indicate that immunization with relatively large antigenic mass combined with an adjuvant is capable of inducing strong active antibody responses in ewes and passively immunizing lambs.

Safety and Immunogenicity of a Mycoplasma ovipneumoniae Bacterin for Domestic Sheep (Ovis aries)

PubMed Central

Ziegler, Jessie C.; Lahmers, Kevin K.; Barrington, George M.; Parish, Steven M.; Kilzer, Katherine; Baker, Katherine; Besser, Thomas E.

2014-01-01

Background Mortality from epizootic pneumonia is hindering re-establishment of bighorn sheep populations in western North America. Mycoplasma ovipneumoniae, a primary agent of this disease, is frequently carried asymptomatically by the domestic sheep and goats that constitute the reservoir of this agent for transmission to bighorn sheep. Our long-term objective is to reduce the risk of M. ovipneumoniae infection of bighorn sheep; one approach to this objective is to control the pathogen in its reservoir hosts. Methods The safety and immunogenicity of M. ovipneumoniae for domestic sheep was evaluated in three experimental immunization protocols: 1) live M. ovipneumoniae (50 ug protein); 2) killed M. ovipneumoniae (50 ug whole cell protein) in oil adjuvant; and 3) killed M. ovipneumoniae (250 ug whole cell protein) in oil adjuvant. Immunogenicity was assessed by two serum antibody measures: competitive enzyme-linked immunosorbent assay (cELISA) (experiments 1–3) and serum growth inhibition (Experiment 3). Passive immunogenicity was also assessed in the third experiment using the same assays applied to blood samples obtained from the lambs of immunized ewes. Results and Conclusions Adverse reactions to immunization were generally minor, but local reactions were regularly observed at immunization sites with bacterins in oil adjuvants. No evidence of M. ovipneumoniae specific antibody responses were observed in the first or second experiments and no resistance to colonization was observed in the first experiment. However, the ewes in the third experiment developed strong cELISA serum antibody responses and significant serum M. ovipneumoniae inhibition activity, and these responses were passively transferred to their lambs. The results of these trials indicate that immunization with relatively large antigenic mass combined with an adjuvant is capable of inducing strong active antibody responses in ewes and passively immunizing lambs. PMID:24752006

Guidelines for pre-clinical assessment of the acetylcholine receptor--specific passive transfer myasthenia gravis model-Recommendations for methods and experimental designs.

PubMed

Kusner, Linda L; Losen, Mario; Vincent, Angela; Lindstrom, Jon; Tzartos, Socrates; Lazaridis, Konstantinos; Martinez-Martinez, Pilar

2015-08-01

Antibodies against the muscle acetylcholine receptor (AChR) are the most common cause of myasthenia gravis (MG). Passive transfer of AChR antibodies from MG patients into animals reproduces key features of human disease, including antigenic modulation of the AChR, complement-mediated damage of the neuromuscular junction, and muscle weakness. Similarly, AChR antibodies generated by active immunization in experimental autoimmune MG models can subsequently be passively transferred to other animals and induce weakness. The passive transfer model is useful to test therapeutic strategies aimed at the effector mechanism of the autoantibodies. Here we summarize published and unpublished experience using the AChR passive transfer MG model in mice, rats and rhesus monkeys, and give recommendations for the design of preclinical studies in order to facilitate translation of positive and negative results to improve MG therapies. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Passive immunization of pigeons against trichomoniasis

USGS Publications Warehouse

Kocan, R.M.

1970-01-01

Nonimmune homing pigeons Columba livia were infected with the Jones' Barn strain of Trichomonas gallinae and subsequently transfused with plasma from acute or chronically infected pigeons harboring one of 3 different strains of T. gallinae. The transfusions were either a single 2 mi dose given one day after inoculation or three 1 ml doses given 0, 5, and 10 days after inoculation. Plasma from pigeons harboring any of the 3 strains was capable of passively immunizing nonimmune birds. All birds which were immunized with plasma from infected pigeons survived until killed at the end of the test period and no visceral lesions were found on necropsy but trichomonads were present in the oropharynx. All controls (untreated or transfused with normal plasma) died of visceral trichomoniasis. Immune plasma produced some lysis of trichomonads in vitro, and inhibition of motility and vacuolization occurred in some of the non-lysed organisms. The overall lytic activity in vitro affected less than 10% of the suspended trichomonads.

Passive Immunization with a Polyclonal Antiserum to the Hemoglobin Receptor of Haemophilus ducreyi Confers Protection against a Homologous Challenge in the Experimental Swine Model of Chancroid▿

PubMed Central

Leduc, Isabelle; Fusco, William G.; Choudhary, Neelima; Routh, Patty A.; Cholon, Deborah M.; Hobbs, Marcia M.; Almond, Glen W.; Orndorff, Paul E.; Elkins, Christopher

2011-01-01

Haemophilus ducreyi, the etiologic agent of chancroid, has an obligate requirement for heme. Heme is acquired by H. ducreyi from its human host via TonB-dependent transporters expressed at its bacterial surface. Of 3 TonB-dependent transporters encoded in the genome of H. ducreyi, only the hemoglobin receptor, HgbA, is required to establish infection during the early stages of the experimental human model of chancroid. Active immunization with a native preparation of HgbA (nHgbA) confers complete protection in the experimental swine model of chancroid, using either Freund's or monophosphoryl lipid A as adjuvants. To determine if transfer of anti-nHgbA serum is sufficient to confer protection, a passive immunization experiment using pooled nHgbA antiserum was conducted in the experimental swine model of chancroid. Pigs receiving this pooled nHgbA antiserum were protected from a homologous, but not a heterologous, challenge. Passively transferred polyclonal antibodies elicited to nHgbA bound the surface of H. ducreyi and partially blocked hemoglobin binding by nHgbA, but were not bactericidal. Taken together, these data suggest that the humoral immune response to the HgbA vaccine is protective against an H. ducreyi infection, possibly by preventing acquisition of the essential nutrient heme. PMID:21646451

Passive immunization with a polyclonal antiserum to the hemoglobin receptor of Haemophilus ducreyi confers protection against a homologous challenge in the experimental swine model of chancroid.

PubMed

Leduc, Isabelle; Fusco, William G; Choudhary, Neelima; Routh, Patty A; Cholon, Deborah M; Hobbs, Marcia M; Almond, Glen W; Orndorff, Paul E; Elkins, Christopher

2011-08-01

Haemophilus ducreyi, the etiologic agent of chancroid, has an obligate requirement for heme. Heme is acquired by H. ducreyi from its human host via TonB-dependent transporters expressed at its bacterial surface. Of 3 TonB-dependent transporters encoded in the genome of H. ducreyi, only the hemoglobin receptor, HgbA, is required to establish infection during the early stages of the experimental human model of chancroid. Active immunization with a native preparation of HgbA (nHgbA) confers complete protection in the experimental swine model of chancroid, using either Freund's or monophosphoryl lipid A as adjuvants. To determine if transfer of anti-nHgbA serum is sufficient to confer protection, a passive immunization experiment using pooled nHgbA antiserum was conducted in the experimental swine model of chancroid. Pigs receiving this pooled nHgbA antiserum were protected from a homologous, but not a heterologous, challenge. Passively transferred polyclonal antibodies elicited to nHgbA bound the surface of H. ducreyi and partially blocked hemoglobin binding by nHgbA, but were not bactericidal. Taken together, these data suggest that the humoral immune response to the HgbA vaccine is protective against an H. ducreyi infection, possibly by preventing acquisition of the essential nutrient heme.

Annual Progress Report - Fiscal Year 1982

DTIC Science & Technology

1982-10-01

activity . A published method developed in our laboratory for determining tne antibacterial activity of mouse peritoneal phagocytes in vivo (1) has been...EDITOR’S NOTE This FY 1982 Annual Progress report is a general review of research activities of the U. S. Army Medical Research Institute of Infectious...years earlier. Passive immunization, active immunization using killed or living attenuated whole agent, or immunization with sub-unit antigens achieved

The abolition of the protective effect of Pasteurella septica antiserum by iron compounds

PubMed Central

Bullen, J. J.; Wilson, A. B.; Cushnie, G. H.; Rogers, Henry J.

1968-01-01

Ferric ammonium citrate, haematin hydrochloride, soluble haematin, lysed mouse red cells and a variety of purified haemoglobins abolished the protective effect of Pasteurella septica antiserum in mice when the iron compounds were injected intraperitoneally with P. septica. Ferric ammonium citrate was less effective than haematin or lysed red cells when the dose of P. septica was reduced to less than 105. The ability of lysed red cells to abolish protection was greatly reduced if given 4 hours or more after infection. P. septica grew rapidly in unimmunized normal mice. In passively immunized mice the number of viable bacteria declined rapidly after infection. In passively immunized mice given haematin or lysed red cells the growth of bacteria was identical to that seen in unprotected normal mice. Large numbers of dead P. septica or carbon particles did not interfere with passive protection. PMID:5661980

Evaluation of lipopolysaccharide and capsular polysaccharide as subunit vaccines against experimental melioidosis.

PubMed

Nelson, Michelle; Prior, Joann L; Lever, M Stephen; Jones, Helen E; Atkins, Timothy P; Titball, Richard W

2004-12-01

Burkholderia pseudomallei is the causative agent of melioidosis, which is a major cause of morbidity and mortality in endemic regions. Currently there is no human vaccine against melioidosis. In this study, LPS or capsular polysaccharide was used to immunize BALB/c mice. The different polysaccharide antigens induced antibody responses. Mice vaccinated with LPS developed predominantly IgM and IgG3 responses. Contrastingly, mice vaccinated with capsular polysaccharide developed a predominantly IgG2b response. After immunization, mice were challenged by the intra-peritoneal route and an increased mean time to death was observed compared with unvaccinated controls. Immunization with LPS provided an optimal protective response. Mice challenged by the aerosol route showed a small increase in the mean time to death compared with the unvaccinated controls. The passive transfer of antigen from immunized into naive mice provided protection against a subsequent challenge. This study is the first time antigens protective by active immunization have been identified and suggests that polysaccharides have potential as vaccine candidates against melioidosis.

Maternal immunization with a DNA vaccine candidate elicits specific passive protection against post-natal Zika virus infection in immunocompetent BALB/c mice.

PubMed

Wang, Ran; Liao, Xianzheng; Fan, Dongying; Wang, Lei; Song, Ji; Feng, Kaihao; Li, Mingyuan; Wang, Peigang; Chen, Hui; An, Jing

2018-06-07

Zika virus (ZIKV) infection is closely associated in the fetus with microcephaly and in the adults with Guillain-Barré syndrome and even male infertility. It is an urgent international priority to develop a safe and effective vaccine that offers protection to both women of childbearing age and their children. In this study, female immunocompetent BALB/c mice were immunized with a DNA-based vaccine candidate, pVAX1-ZME, expressing the prM/E protein of ZIKV, and the immunogenicity for maternal mice and the post-natal protection for suckling mice were evaluated. It was found that administration with three doses of 50 μg pVAX1-ZME via in vivo electroporation induced robust ZIKV-specific cellular and long-term humoral immune responses with high and sustained neutralizing activity in adult mice. Moreover, using a maternal immunization protocol, neutralizing antibodies provided specific passive protection against ZIKV infection in neonatal mice and effectively inhibited the growth delay. This vaccine candidate is expected to be further evaluated in higher animals, and maternal vaccination shows great promise for protecting both women of childbearing age and their offspring against post-natal ZIKV infection. The vaccinated mothers and ZIKV-challenged pups provide key insight into Zika vaccine evaluation in an available fully immunocompetent animal model. Copyright © 2018 Elsevier Ltd. All rights reserved.

Intestinal infection with Trichinella spiralis induces distinct, regional immune responses

PubMed Central

Blum, L.K.; Mohanan, S.; Fabre, M.V.; Yafawi, R.E.; Appleton, J.A.

2013-01-01

The aim of this study was to evaluate differences between the small and large intestines (SI and LI) with regard to colonization and immunity during infection with Trichinella spiralis. In orally infected C57BL/6 mice, the gender ratios of worms differed among the SI, cecum, and LI. Mucosal mastocytosis developed in the SI but not in the LI, consistent with reduced IL-9 and IL-13 production by explants from the LI. Despite these differences, worms were cleared at the same rate from both sites. Furthermore, IL-10 production was reduced in the LI, yet it was instrumental in limiting local inflammation. Finally, passive immunization of rat pups with tyvelose-specific antibodies effectively cleared fist-stage larvae from all intestinal regions. We conclude that despite regional differences in immune responsiveness and colonization, immune mechanisms that clear T. spiralis operate effectively throughout the intestinal tract. PMID:23465441

Pathophysiology of infectious hematopoietic necrosis virus disease in rainbow trout (Salmo gairdneri): early changes in blood and aspects of the immune Response after Injection of IHN Virus

USGS Publications Warehouse

Amend, Donald F.; Smith, Lynnwood

1974-01-01

Juvenile rainbow trout (Salmo gairdneri) were injected with infectious hematopoietic necrosis (IHN) virus and various hematological and blood chemical changes were monitored over 9 days. The packed cell volume, hemoglobin, red blood cell count, and plasma bicarbonate were significantly depressed by day 4. Plasma chloride, calcium, phosphorus, total protein, and blood cell types did not change during the 9 days. Furthermore, plasma  LDH isozyme was significantly increased by the fourth day, and fish infected with infectious pancreatic necrosis virus, Vibrio anguillarum, Aeromonas salmonicida, and redmouth bacterium did not show specific LDH isozyme alterations. Acid-base alterations occurred at 10 C but not at 18 C. The acid-base imbalance and elevation of the  LDH isozyme were consistently associated with the early development of the disease.The immune response after injection of IHN virus was determined and protection from disease was tested by passive immunization. Actively immunized fish developed IHN-neutralizing antibodies within 54 days after injection of virus, and the antibodies were protective when juvenile fish were passively immunized and experimentally challenged with IHN virus.

Monoclonal antibodies passively protect BALB/c mice against Burkholderia mallei aerosol challenge.

PubMed

Treviño, Sylvia R; Permenter, Amy R; England, Marilyn J; Parthasarathy, Narayanan; Gibbs, Paul H; Waag, David M; Chanh, Tran C

2006-03-01

Glanders is a debilitating disease with no vaccine available. Murine monoclonal antibodies were produced against Burkholderia mallei, the etiologic agent of glanders, and were shown to be effective in passively protecting mice against a lethal aerosol challenge. The antibodies appeared to target lipopolysaccharide. Humoral antibodies may be important for immune protection against B. mallei infection.

Vaccination for the prevention of maternal and fetal infection with guinea pig cytomegalovirus.

PubMed

Bia, F J; Griffith, B P; Tarsio, M; Hsiung, G D

1980-11-01

Live guinea pig cytomegalovirus (CMV) vaccine was prepared after 11 serial passages in tissue culture; noninfectious envelope antigen vaccine was prepared by n-octyl glucoside treatment of CMV-derived dense bodies and virions. Hartley strain guinea pigs immunized with either vaccine were compared with guinea pigs inoculated with virulent, salivary gland-passaged CMV (approximating natural infection), with passively immunized animals, and with nonimmune controls. All vaccinated animals had neutralizing antibodies to CMV. After challenge with virulent CMV, animals previously inoculated with either tissue culture-passaged or virulent CMV were protected against acute viremia and death; pregnant animals previously inoculated with live CMV vaccine had lower incidences of viremia and generalized maternal and fetal infection. Envelope antigen-vaccinated and passively immunized pregnant animals showed acute viremia after similar challenge with virulent virus; however, infection was less generalized than that in control animals, and CMV was not isolated from the fetuses of these vaccinated mothers.

T cells play an essential role in anti-F1 mediated rapid protection against bubonic plague.

PubMed

Levy, Yinon; Flashner, Yehuda; Tidhar, Avital; Zauberman, Ayelet; Aftalion, Moshe; Lazar, Shirley; Gur, David; Shafferman, Avigdor; Mamroud, Emanuelle

2011-09-16

Plague, which is initiated by Yersinia pestis infection, is a fatal disease that progresses rapidly and leads to high mortality rates if not treated. Antibiotics are an effective plague therapy, but antibiotic-resistant Y. pestis strains have been reported and therefore alternative countermeasures are needed. In the present study, we assessed the potential of an F1 plus LcrV-based vaccine to provide protection shortly pre- or post-exposure to a lethal Y. pestis infection. Mice vaccinated up to one day before or even several hours after subcutaneous challenge were effectively protected. Mice immunized one or three days pre-challenge were protected even though their anti-F1 and anti-LcrV titers were below detection levels at the day of challenge. Moreover, using B-cell deficient μMT mice, we found that rapidly induced protective immunity requires the integrity of the humoral immune system. Analysis of the individual contributions of vaccine components to protection revealed that rF1 is responsible for the observed rapid antibody-mediated immunity. Applying anti-F1 passive therapy in the mouse model of bubonic plague demonstrated that anti-F1 F(ab')(2) can delay mortality, but it cannot provide long-lasting protection, as do intact anti-F1 molecules. Fc-dependent immune components, such as the complement system and (to a lesser extent) neutrophils, were found to contribute to mouse survival. Interestingly, T cells but not B cells were found to be essential for the recovery of infected animals following passive anti-F1 mediated therapy. These data extend our understanding of the immune mechanisms required for the development of a rapid and effective post-exposure therapy against plague. Copyright © 2011 Elsevier Ltd. All rights reserved.

Skin Immune Landscape: Inside and Outside the Organism.

PubMed

Abdallah, Florence; Mijouin, Lily; Pichon, Chantal

2017-01-01

The skin is an essential organ to the human body protecting it from external aggressions and pathogens. Over the years, the skin was proven to have a crucial immunological role, not only being a passive protective barrier but a network of effector cells and molecular mediators that constitute a highly sophisticated compound known as the "skin immune system" (SIS). Studies of skin immune sentinels provided essential insights of a complex and dynamic immunity, which was achieved through interaction between the external and internal cutaneous compartments. In fact, the skin surface is cohabited by microorganisms recognized as skin microbiota that live in complete harmony with the immune sentinels and contribute to the epithelial barrier reinforcement. However, under stress, the symbiotic relationship changes into a dysbiotic one resulting in skin disorders. Hence, the skin microbiota may have either positive or negative influence on the immune system. This review aims at providing basic background information on the cutaneous immune system from major cellular and molecular players and the impact of its microbiota on the well-coordinated immune responses in host defense.

The neuroendocrine immunomodulatory axis-like pathway mediated by circulating haemocytes in pacific oyster Crassostrea gigas.

PubMed

Liu, Zhaoqun; Zhou, Zhi; Jiang, Qiufen; Wang, Lingling; Yi, Qilin; Qiu, Limei; Song, Linsheng

2017-01-01

The neuroendocrine-immune (NEI) regulatory network is a complex system, which plays an indispensable role in the immunity of host. In this study, a neuroendocrine immunomodulatory axis (NIA)-like pathway mediated by the nervous system and haemocytes was characterized in the oyster Crassostrea gigas Once invaded pathogen was recognized by the host, the nervous system would temporally release neurotransmitters to modulate the immune response. Instead of acting passively, oyster haemocytes were able to mediate neuronal immunomodulation promptly by controlling the expression of specific neurotransmitter receptors on cell surface and modulating their binding sensitivities, thus regulating intracellular concentration of Ca 2+ This neural immunomodulation mediated by the nervous system and haemocytes could influence cellular immunity in oyster by affecting mRNA expression level of TNF genes, and humoral immunity by affecting the activities of key immune-related enzymes. In summary, though simple in structure, the 'nervous-haemocyte' NIA-like pathway regulates both cellular and humoral immunity in oyster, meaning a world to the effective immune regulation of the NEI network. © 2017 The Authors.

C60 fullerene localization and membrane interactions in RAW 264.7 immortalized mouse macrophages

NASA Astrophysics Data System (ADS)

Russ, K. A.; Elvati, P.; Parsonage, T. L.; Dews, A.; Jarvis, J. A.; Ray, M.; Schneider, B.; Smith, P. J. S.; Williamson, P. T. F.; Violi, A.; Philbert, M. A.

2016-02-01

There continues to be a significant increase in the number and complexity of hydrophobic nanomaterials that are engineered for a variety of commercial purposes making human exposure a significant health concern. This study uses a combination of biophysical, biochemical and computational methods to probe potential mechanisms for uptake of C60 nanoparticles into various compartments of living immune cells. Cultures of RAW 264.7 immortalized murine macrophage were used as a canonical model of immune-competent cells that are likely to provide the first line of defense following inhalation. Modes of entry studied were endocytosis/pinocytosis and passive permeation of cellular membranes. The evidence suggests marginal uptake of C60 clusters is achieved through endocytosis/pinocytosis, and that passive diffusion into membranes provides a significant source of biologically-available nanomaterial. Computational modeling of both a single molecule and a small cluster of fullerenes predicts that low concentrations of fullerenes enter the membrane individually and produce limited perturbation; however, at higher concentrations the clusters in the membrane causes deformation of the membrane. These findings are bolstered by nuclear magnetic resonance (NMR) of model membranes that reveal deformation of the cell membrane upon exposure to high concentrations of fullerenes. The atomistic and NMR models fail to explain escape of the particle out of biological membranes, but are limited to idealized systems that do not completely recapitulate the complexity of cell membranes. The surprising contribution of passive modes of cellular entry provides new avenues for toxicological research that go beyond the pharmacological inhibition of bulk transport systems such as pinocytosis.There continues to be a significant increase in the number and complexity of hydrophobic nanomaterials that are engineered for a variety of commercial purposes making human exposure a significant health concern. This study uses a combination of biophysical, biochemical and computational methods to probe potential mechanisms for uptake of C60 nanoparticles into various compartments of living immune cells. Cultures of RAW 264.7 immortalized murine macrophage were used as a canonical model of immune-competent cells that are likely to provide the first line of defense following inhalation. Modes of entry studied were endocytosis/pinocytosis and passive permeation of cellular membranes. The evidence suggests marginal uptake of C60 clusters is achieved through endocytosis/pinocytosis, and that passive diffusion into membranes provides a significant source of biologically-available nanomaterial. Computational modeling of both a single molecule and a small cluster of fullerenes predicts that low concentrations of fullerenes enter the membrane individually and produce limited perturbation; however, at higher concentrations the clusters in the membrane causes deformation of the membrane. These findings are bolstered by nuclear magnetic resonance (NMR) of model membranes that reveal deformation of the cell membrane upon exposure to high concentrations of fullerenes. The atomistic and NMR models fail to explain escape of the particle out of biological membranes, but are limited to idealized systems that do not completely recapitulate the complexity of cell membranes. The surprising contribution of passive modes of cellular entry provides new avenues for toxicological research that go beyond the pharmacological inhibition of bulk transport systems such as pinocytosis. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr07003a

MEDI4893* Promotes Survival and Extends the Antibiotic Treatment Window in a Staphylococcus aureus Immunocompromised Pneumonia Model

PubMed Central

Hua, L.; Cohen, T. S.; Shi, Y.; Datta, V.; Hilliard, J. J.; Tkaczyk, C.; Suzich, J.; Stover, C. K.

2015-01-01

Immunocompromised individuals are at increased risk of Staphylococcus aureus pneumonia. Neutralization of alpha-toxin (AT) with the monoclonal antibody (MAb) MEDI4893* protects normal mice from S. aureus pneumonia; however, the effects of the MAb in immunocompromised mice have not been reported. In this study, passive immunization with MEDI4893* increased survival rates and reduced bacterial numbers in the lungs in an immunocompromised murine S. aureus pneumonia model. Lungs from infected mice exhibited alveolar epithelial damage, protein leakage, and bacterial overgrowth, whereas lungs from mice passively immunized with MEDI4893* retained a healthy architecture, with an intact epithelial barrier. Adjunctive therapy or prophylaxis with a subtherapeutic MEDI4893* dose combined with subtherapeutic doses of vancomycin or linezolid improved survival rates, compared with the monotherapies. Furthermore, coadministration of MEDI4893* with vancomycin or linezolid extended the antibiotic treatment window. These data suggest that MAb-mediated neutralization of AT holds promise in strategies for prevention and adjunctive therapy among immunocompromised patients. PMID:25987629

Cellular responses to Mycobacterium avium, subsp. paratuberculosis in colostrum-deprived and colostrum-replete holstein calves supplemented with fat-soluble vitamins

USDA-ARS?s Scientific Manuscript database

Immune benefits of colostrum are attributed to passively transferred IgG but also to growth factors, cytokines, antimicrobial peptides, and leukocytes. Non-nutritive compounds in colostrum promote Th2-biased immune responses to early microbial encounters and prevent harmful, inappropriate inflammat...

Passive immunization of Pacific herring against viral hemorrhagic septicemia.

USGS Publications Warehouse

Hershberger, P.K.; Gregg, J.L.; Grady, C.A.; LaPatra, S.E.; Winton, J.R.

2011-01-01

The plasma of Pacific herring Clupea pallasii that survived laboratory-induced viral hemorrhagic septicemia (VHS) epizootics contained humoral substances that, when injected into naive animals, conferred passive immunity against the disease. Among groups exposed to viral hemorrhagic septicemia virus (VHSV), injection of donor plasma from VHS survivors resulted in significantly greater survival (50%) and significantly lower tissue titers (1.5 x 10(5) plaque-forming units [PFU]/g) than the injection of plasma from VHSV-naive donors (6% survival; 3.7 x 10(6) PFU/g). Additionally, the magnitude of the protective immune response increased during the postexposure period; plasma that was collected from survivors at 123 d postexposure (931 degree-days) provided greater protection than plasma collected from survivors at 60 d postexposure (409 degree-days). These results provide proof of concept that the VHSV exposure history of Pacific herring populations can be determined post hoc; furthermore, the results can be used as the foundation for developing additional high-throughput diagnostic techniques that may be effective at quantifying herd immunity and forecasting the potential for future VHS epizootics in populations of wild Pacific herring.

Engineered Mesenchymal Cells Improve Passive Immune Protection Against Lethal Venezuelan Equine Encephalitis Virus Exposure

PubMed Central

Braid, Lorena R.; Davies, John E.; Nagata, Les P.

2016-01-01

Mesenchymal stromal cells (MSCs) are being exploited as gene delivery vectors for various disease and injury therapies. We provide proof-of-concept that engineered MSCs can provide a useful, effective platform for protection against infectious disease. Venezuelan equine encephalitis virus (VEEV) is a mosquito-borne pathogen affecting humans and equines and can be used in bio-warfare. No licensed vaccine or antiviral agent currently exists to combat VEEV infection in humans. Direct antibody administration (passive immunity) is an effective, but short-lived, method of providing immediate protection against a pathogen. We compared the protective efficacy of human umbilical cord perivascular cells (HUCPVCs; a rich source of MSCs), engineered with a transgene encoding a humanized VEEV-neutralizing antibody (anti-VEEV), to the purified antibody. In athymic mice, the anti-VEEV antibody had a half-life of 3.7 days, limiting protection to 2 or 3 days after administration. In contrast, engineered HUCPVCs generated protective anti-VEEV serum titers for 21–38 days after a single intramuscular injection. At 109 days after transplantation, 10% of the mice still had circulating anti-VEEV antibody. The mice were protected against exposure to a lethal dose of VEEV by an intramuscular pretreatment injection with engineered HUCPVCs 24 hours or 10 days before exposure, demonstrating both rapid and prolonged immune protection. The present study is the first to describe engineered MSCs as gene delivery vehicles for passive immunity and supports their utility as antibody delivery vehicles for improved, single-dose prophylaxis against endemic and intentionally disseminated pathogens. Significance Direct injection of monoclonal antibodies (mAbs) is an important strategy to immediately protect the recipient from a pathogen. This strategy is critical during natural outbreaks or after the intentional release of bio-weapons. Vaccines require weeks to become effective, which is not practical for first responders immediately deployed to an infected region. However, mAb recipients often require booster shots to maintain protection, which is expensive and impractical once the first responders have been deployed. The present study has shown, for the first time, that mesenchymal stromal cells are effective gene delivery vehicles that can significantly improve mAb-mediated immune protection in a single, intramuscular dose of engineered cells. Such a cell-based delivery system can provide extended life-saving protection in the event of exposure to biological threats using a more practical, single-dose regimen. PMID:27334491

Role of Homologous Fc Fragment in the Potency and Efficacy of Anti-Botulinum Antibody Preparations.

PubMed

Torgeman, Amram; Ozeri, Eyal; Ben David, Alon; Diamant, Eran; Rosen, Osnat; Schwartz, Arieh; Barnea, Ada; Makovitzki, Arik; Mimran, Avishai; Zichel, Ran

2017-05-29

The only approved treatment for botulism relies on passive immunity which is mostly based on antibody preparations collected from hyper-immune horses. The IgG Fc fragment is commonly removed from these heterologous preparations to reduce the incidence of hyper-sensitivity reactions. New-generation therapies entering the pipeline are based on a combination of humanized monoclonal antibodies (MAbs), which exhibit improved safety and pharmacokinetics. In the current study, a systematic and quantitative approach was applied to measure the direct contribution of homologous Fc to the potency of monoclonal and polyclonal antitoxin preparations in mice. Homologous Fc increased the potency of three individual anti-botulinum toxin MAbs by up to one order of magnitude. Moreover, Fc fragment removal almost completely abolished the synergistic potency obtained from a combined preparation of these three MAbs. The MAb mixture neutralized a 400-mouse median lethal dose (MsLD50) of botulinum toxin, whereas the F(ab')2 combination failed to neutralize 10 MsLD50 of botulinum toxin. Notably, increased avidity did not compensate for this phenomenon, as a polyclonal, hyper-immune, homologous preparation lost 90% of its potency as well upon Fc removal. Finally, the addition of homologous Fc arms to a heterologous pharmaceutical anti-botulinum toxin polyclonal horse F(ab')2 preparation improved its efficacy when administered to intoxicated symptomatic mice. Our study extends the aspects by which switching from animal-based to human-based antitoxins will improve not only the safety but also the potency and efficacy of passive immunity against toxins.

Passive serum therapy with polyclonal antibodies against Mycobacterium tuberculosis protects against post-chemotherapy relapse of tuberculosis infection in SCID mice.

PubMed

Guirado, Evelyn; Amat, Isabel; Gil, Olga; Díaz, Jorge; Arcos, Virginia; Caceres, Neus; Ausina, Vicenç; Cardona, Pere-Joan

2006-04-01

We investigated the protective role of immune-sera against reactivation of Mycobacterium tuberculosis infection in SCID mice and found that passive immunization with sera obtained from mice treated with detoxified M. tuberculosis extracts (delivered in liposomes in a composition known as RUTI) exerted significant protection. Our SCID mouse model consisted of aerosol infection by M. tuberculosis, followed by 3 to 8weeks of chemotherapy with isoniazid+rifampicin (INH+RIF) (25 and 10mg/kg, respectively). After infection and antibiotic administration, two groups of mice were treated for up to 10weeks with intraperitoneal passive immunization using hyperimmune serum (HS) obtained from mice infected with M. tuberculosis, treated with chemotherapy (INH+RIF) for 8weeks and inoculated with RUTI (HS group) or with normal serum (CT group). Significant differences were found between HS and CT groups in the number of bacilli in the lungs (3.68+/-2.02 vs. 5.72+/-1.41log(10) c.f.u.), extent of pulmonary granulomatomous infiltration (10.33+/-0.67 vs. 31.2+/-1.77%), and percentage of animals without pulmonary abscesses (16.7% vs. 45.5%). These data strongly suggest a protective role of specific antibodies against lung dissemination of M. tuberculosis infection.

Evaluation of Neisseria Gonorrhoeae Opacity (Opa) Protein Loops as Targets for Passive Vaccination and Investigation of the Role of Opa Proteins During Infection of a Female Host

DTIC Science & Technology

2009-08-24

Bourne, N., R. B. Pyles, D. I. Bernstein, and L. R. Stanberry. 2002. Modification of primary and recurrent genital herpes in guinea pigs by passive...Barratt, T. E. Hoen, and R. A. Cone. 1994. Passive immunization of the vagina protects mice against vaginal transmission of genital herpes ...and investigations into the role of Opa proteins during infection of the female genital tract. We demonstrated antibodies that target conserved Opa

Past, present and future targets for immunotherapy in ovarian cancer

PubMed Central

Schwab, Carlton L; English, Diana P; Roque, Dana M; Pasternak, Monica; Santin, Alessandro D

2015-01-01

Ovarian cancer is the leading cause of death from gynecologic malignancy in the US. Treatments have improved with conventional cytotoxic chemotherapy and advanced surgical techniques but disease recurrence is common and fatal in nearly all cases. Current evidence suggests that the immune system and its ability to recognize and eliminate microscopic disease is paramount in preventing recurrence. Ovarian cancer immunotherapy is targeting tumors through active, passive and adoptive approaches. The goal of immunotherapy is to balance the activation of the immune system against cancer while preventing the potential for tremendous toxicity elicited by immune modulation. In this paper we will review the different immunotherapies available for ovarian cancer as well as current ongoing studies and potential future directions. PMID:25524384

Social Transfer of Pathogenic Fungus Promotes Active Immunisation in Ant Colonies

PubMed Central

Konrad, Matthias; Vyleta, Meghan L.; Theis, Fabian J.; Stock, Miriam; Tragust, Simon; Klatt, Martina; Drescher, Verena; Marr, Carsten; Ugelvig, Line V.; Cremer, Sylvia

2012-01-01

Due to the omnipresent risk of epidemics, insect societies have evolved sophisticated disease defences at the individual and colony level. An intriguing yet little understood phenomenon is that social contact to pathogen-exposed individuals reduces susceptibility of previously naive nestmates to this pathogen. We tested whether such social immunisation in Lasius ants against the entomopathogenic fungus Metarhizium anisopliae is based on active upregulation of the immune system of nestmates following contact to an infectious individual or passive protection via transfer of immune effectors among group members—that is, active versus passive immunisation. We found no evidence for involvement of passive immunisation via transfer of antimicrobials among colony members. Instead, intensive allogrooming behaviour between naive and pathogen-exposed ants before fungal conidia firmly attached to their cuticle suggested passage of the pathogen from the exposed individuals to their nestmates. By tracing fluorescence-labelled conidia we indeed detected frequent pathogen transfer to the nestmates, where they caused low-level infections as revealed by growth of small numbers of fungal colony forming units from their dissected body content. These infections rarely led to death, but instead promoted an enhanced ability to inhibit fungal growth and an active upregulation of immune genes involved in antifungal defences (defensin and prophenoloxidase, PPO). Contrarily, there was no upregulation of the gene cathepsin L, which is associated with antibacterial and antiviral defences, and we found no increased antibacterial activity of nestmates of fungus-exposed ants. This indicates that social immunisation after fungal exposure is specific, similar to recent findings for individual-level immune priming in invertebrates. Epidemiological modeling further suggests that active social immunisation is adaptive, as it leads to faster elimination of the disease and lower death rates than passive immunisation. Interestingly, humans have also utilised the protective effect of low-level infections to fight smallpox by intentional transfer of low pathogen doses (“variolation” or “inoculation”). PMID:22509134

Preterm Birth Affects the Risk of Developing Immune-Mediated Diseases

PubMed Central

Goedicke-Fritz, Sybelle; Härtel, Christoph; Krasteva-Christ, Gabriela; Kopp, Matthias V.; Meyer, Sascha; Zemlin, Michael

2017-01-01

Prematurity affects approximately 10% of all children, resulting in drastically altered antigen exposure due to premature confrontation with microbes, nutritional antigens, and other environmental factors. During the last trimester of pregnancy, the fetal immune system adapts to tolerate maternal and self-antigens, while also preparing for postnatal immune defense by acquiring passive immunity from the mother. Since the perinatal period is regarded as the most important “window of opportunity” for imprinting metabolism and immunity, preterm birth may have long-term consequences for the development of immune-mediated diseases. Intriguingly, preterm neonates appear to develop bronchial asthma more frequently, but atopic dermatitis less frequently in comparison to term neonates. The longitudinal study of preterm neonates could offer important insights into the process of imprinting for immune-mediated diseases. On the one hand, preterm birth may interrupt influences of the intrauterine environment on the fetus that increase or decrease the risk of later immune disease (e.g., maternal antibodies and placenta-derived factors), whereas on the other hand, it may lead to the premature exposure to protective or harmful extrauterine factors such as microbiota and nutritional antigen. Solving this puzzle may help unravel new preventive and therapeutic approaches for immune diseases. PMID:29062316

Vaccination for protection of retinal ganglion cells against death from glutamate cytotoxicity and ocular hypertension: Implications for glaucoma

NASA Astrophysics Data System (ADS)

Schori, Hadas; Kipnis, Jonathan; Yoles, Eti; Woldemussie, Elizabeth; Ruiz, Guadalupe; Wheeler, Larry A.; Schwartz, Michal

2001-03-01

Our group recently demonstrated that autoimmune T cells directed against central nervous system-associated myelin antigens protect neurons from secondary degeneration. We further showed that the synthetic peptide copolymer 1 (Cop-1), known to suppress experimental autoimmune encephalomyelitis, can be safely substituted for the natural myelin antigen in both passive and active immunization for neuroprotection of the injured optic nerve. Here we attempted to determine whether similar immunizations are protective from retinal ganglion cell loss resulting from a direct biochemical insult caused, for example, by glutamate (a major mediator of degeneration in acute and chronic optic nerve insults) and in a rat model of ocular hypertension. Passive immunization with T cells reactive to myelin basic protein or active immunization with myelin oligodendrocyte glycoprotein-derived peptide, although neuroprotective after optic nerve injury, was ineffective against glutamate toxicity in mice and rats. In contrast, the number of surviving retinal ganglion cells per square millimeter in glutamate-injected retinas was significantly larger in mice immunized 10 days previously with Cop-1 emulsified in complete Freund's adjuvant than in mice injected with PBS in the same adjuvant (2,133 ± 270 and 1,329 ± 121, respectively, mean ± SEM; P < 0.02). A similar pattern was observed when mice were immunized on the day of glutamate injection (1,777 ± 101 compared with 1,414 ± 36; P <0.05), but not when they were immunized 48h later. These findings suggest that protection from glutamate toxicity requires reinforcement of the immune system by antigens that are different from those associated with myelin. The use of Cop-1 apparently circumvents this antigen specificity barrier. In the rat ocular hypertension model, which simulates glaucoma, immunization with Cop-1 significantly reduced the retinal ganglion cell loss from 27.8%±6.8% to 4.3%±1.6%, without affecting the intraocular pressure. This study may point the way to a therapy for glaucoma, a neurodegenerative disease of the optic nerve often associated with increased intraocular pressure, as well as for acute and chronic degenerative disorders in which glutamate is a prominent participant.

Immune correlates of protection against yellow fever determined by passive immunization and challenge in the hamster model.

PubMed

Julander, Justin G; Trent, Dennis W; Monath, Thomas P

2011-08-11

Live, attenuated yellow fever (YF) 17D vaccine is highly efficacious but causes rare, serious adverse events resulting from active replication in the host and direct viral injury to vital organs. We recently reported development of a potentially safer β-propiolactone-inactivated whole virion YF vaccine (XRX-001), which was highly immunogenic in mice, hamsters, monkeys, and humans [10,11]. To characterize the protective efficacy of neutralizing antibodies stimulated by the inactivated vaccine, graded doses of serum from hamsters immunized with inactivated XRX-001 or live 17D vaccine were transferred to hamsters by the intraperitoneal (IP) route 24h prior to virulent, viscerotropic YF virus challenge. Neutralizing antibody (PRNT(50)) titers were determined in the sera of treated animals 4h before challenge and 4 and 21 days after challenge. Neutralizing antibodies were shown to mediate protection. Animals having 50% plaque reduction neutralization test (PRNT(50)) titers of ≥40 4h before challenge were completely protected from disease as evidenced by viremia, liver enzyme elevation, and protection against illness (weight change) and death. Passive titers of 10-20 were partially protective. Immunization with the XRX-001 vaccine stimulated YF neutralizing antibodies that were equally effective (based on dose response) as antibodies stimulated by live 17D vaccine. The results will be useful in defining the level of seroprotection in clinical studies of new yellow fever vaccines. Copyright © 2011 Elsevier Ltd. All rights reserved.

Neutrophils Are Central to Antibody-Mediated Protection against Genital Chlamydia.

PubMed

Naglak, Elizabeth K; Morrison, Sandra G; Morrison, Richard P

2017-10-01

Determining the effector populations involved in humoral protection against genital chlamydia infection is crucial to development of an effective chlamydial vaccine. Antibody has been implicated in protection studies in multiple animal models, and we previously showed that the passive transfer of immune serum alone does not confer immunity in the mouse. Using the Chlamydia muridarum model of genital infection, we demonstrate a protective role for both Chlamydia -specific immunoglobulin G (IgG) and polymorphonuclear neutrophils and show the importance of an antibody/effector cell interaction in mediating humoral immunity. While neutrophils were found to contribute significantly to antibody-mediated protection in vivo , natural killer (NK) cells were dispensable for protective immunity. Furthermore, gamma interferon (IFN-γ)-stimulated primary peritoneal neutrophils (PPNs) killed chlamydiae in vitro in an antibody-dependent manner. The results from this study support the view that an IFN-γ-activated effector cell population cooperates with antibody to protect against genital chlamydia and establish neutrophils as a key effector cell in this response. Copyright © 2017 Naglak et al.

Immunization with the recombinant antigen Ss-IR induces protective immunity to infection with Strongyloides stercoralis in mice.

PubMed

Abraham, David; Hess, Jessica A; Mejia, Rojelio; Nolan, Thomas J; Lok, James B; Lustigman, Sara; Nutman, Thomas B

2011-10-19

Human intestinal infections with the nematode Strongyloides stercoralis remain a significant problem worldwide and a vaccine would be a useful addition to the tools available to prevent and control this infection. The goal of this study was to test single antigens for their efficacy in a vaccine against S. stercoralis larvae in mice. Alum was used as the adjuvant in these studies and antigens selected for analysis were either recognized by protective human IgG (Ss-TMY-1, Ss-EAT-6, and Ss-LEC-5) or were known to be highly immunogenic in humans (Ss-NIE-1 and Ss-IR). Only mice immunized with the Ss-IR antigen demonstrated a significant decrease of approximately 80% in the survival of larval parasites in the challenge infection. Antibodies, recovered from mice with protective immunity to S. stercoralis after immunization with Ss-IR, were used to locate the antigen in the larvae. Confocal microscopy revealed that IgG from mice immunized with Ss-IR bound to the surface of the parasites and observations by electron microscopy indicated that IgG bound to granules in the glandular esophagus. Serum collected from mice immunized with Ss-IR passively transferred immunity to naïve mice. These studies demonstrate that Ss-IR, in combination with alum, induces high levels of protective immunity through an antibody dependent mechanism and may therefore be suitable for further development as a vaccine against human strongyloidiasis. Copyright © 2011 Elsevier Ltd. All rights reserved.

Passive immunization targeting the N-terminal projection domain of tau decreases tau pathology and improves cognition in a transgenic mouse model of Alzheimer disease and tauopathies.

PubMed

Dai, Chun-ling; Chen, Xia; Kazim, Syed Faraz; Liu, Fei; Gong, Cheng-Xin; Grundke-Iqbal, Inge; Iqbal, Khalid

2015-04-01

Intraneuronal accumulation of abnormally hyperphosphorylated tau in the brain is a histopathological hallmark of Alzheimer's disease and a family of related neurodegenerative disorders collectively called tauopathies. At present there is no effective treatment available for these progressive neurodegenerative diseases which are clinically characterized by dementia in mid to old-age. Here we report the treatment of 14-17-months-old 3xTg-AD mice with tau antibodies 43D (tau 6-18) and 77E9 (tau 184-195) to the N-terminal projection domain of tau or mouse IgG as a control by intraperitoneal injection once a week for 4 weeks, and the effects of the passive immunization on reduction of hyperphosphorylated tau, Aβ accumulation and cognitive performance in these animals. We found that treatment with tau antibodies 43D and 77E9 reduced total tau level, decreased tau hyperphosphorylated at Ser199, Ser202/Thr205 (AT8), Thr205, Ser262/356 (12E8), and Ser396/404 (PHF-1) sites, and a trend to reduce Aβ pathology. Most importantly, targeting N-terminal tau especially by 43D (tau 6-18) improved reference memory in the Morris water maze task in 3xTg-AD mice. We did not observe any abnormality in general physical characteristics of the treated animals with either of the two antibodies during the course of this study. Taken together, our studies demonstrate for the first time (1) that passive immunization targeting normal tau can effectively clear the hyperphosphorylated protein and possibly reduce Aβ pathology from the brain and (2) that targeting N-terminal projection domain of tau containing amino acid 6-18 is especially beneficial. Thus, targeting selective epitopes of N-terminal domain of tau may present a novel effective therapeutic opportunity for Alzheimer disease and other tauopathies.

Driving mechanisms of passive and active transport across cellular membranes as the mechanisms of cell metabolism and development as well as the mechanisms of cellular distance reactions on hormonal expression and the immune response.

PubMed

Ponisovskiy, M R

2011-01-01

The article presents mechanisms of cell metabolism, cell development, cell activity, and maintenance of cellular stability. The literature is reviewed from the point of view of these concepts. The balance between anabolic and catabolic processes induces chemical potentials in the extracellular and intracellular media. The chemical potentials of these media are defined as the driving forces of both passive and active transport of substances across cellular membranes. The driving forces of substance transport across cellular membranes as in cellular metabolism and in immune responses and hormonal expressions are considered in the biochemical and biophysical models, reflecting the mechanisms for maintenance of stability of the internal medium and internal energy of an organism. The interactions of passive transport and active transport of substances across cellular walls promote cell proliferation, as well as the mechanism of cellular capacitors, promoting remote reactions across distance for hormonal expression and immune responses. The offered concept of cellular capacitors has given the possibility to explain the mechanism of remote responses of cells to new situations, resulting in the appearance of additional agents. The biophysical model develops an explanation of some cellular functions: cellular membrane action have been identified with capacitor action, based on the similarity of the structures and as well as on similarity of biophysical properties of electric data that confirm the action of the compound-specific interactions of cells within an organism, promoting hormonal expressions and immune responses to stabilize the thermodynamic system of an organism. Comparison of a cellular membrane action to a capacitor has given the possibility for the explanations of exocytosis and endocytosis mechanisms, internalization of the receptor-ligand complex, selection as a receptor reaction to a ligand by immune responses or hormonal effects, reflecting cellular distance reactions on the hormonal expressions, immune responses, and specificity of the mechanisms of immune reactions. Reviewing current research of cell activity, explanations are presented of mechanisms of apoptosis, autophagy, hormonal expression, and immune responses from the point of view of described cellular mechanisms. Thermodynamic laws are used to confirm the importance of the actions of these mechanisms for maintenance of stability of the internal medium and internal energy of an organism.

The passive transfer of immunity to Taenia ovis in lambs via colostrum.

PubMed

Sutton, R J

1979-09-01

Colostrum from ewes that had been repeatedly exposed to cestode infection, whether or not their immunity was boosted by vaccination with Taenia ovis, transferred a strong immunity to the lambs. Susceptible ewes, not recently exposed to tapeworm eggs, gave no protection to their lambs via the colostrum. There was no evidence that colostrum-deprived lambs were more susceptible to infection with T ovis than lambs that received colostrum from non-immune ewes. Colostrum from naturally immune vaccinated ewes gave good protection to lambs for up to six weeks but thereafter the effect was variable. The immunity that developed in susceptible ewes after vaccination with activated embryos was not passed on to the lambs via the colostrum.

Maternal Immunization with Chimpanzee Adenovirus Expressing RSV Fusion Protein Protects Against Neonatal RSV Pulmonary Infection

PubMed Central

Sharma, Anurag; Wendland, Rebecca; Sung, Biin; Wu, Wendy; Grunwald, Thomas; Worgall, Stefan

2014-01-01

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract disease with high morbidity and mortality in young infants and children. Despite numerous efforts, a licensed vaccine against RSV remains elusive. Since young infants form the primary target group of RSV disease, maternal immunization to boost the protection in neonates is an attractive strategy. In this study we tested the efficacy of maternal immunization with a chimpanzee adenovirus expressing codon-optimized RSV fusion protein (AdC7-Fsyn) to protect infants against RSV infection. Single intranasal immunization of mice by AdC7-Fsyn induced robust anti-RSV systemic and mucosal immunity that protected against RSV without causing vaccine-enhanced RSV disease. RSV humoral immunity was transferred to pups born to immunized mothers that provided protection against RSV. Immunization with AdC7-Fsyn was effective even in the presence of Ad5 preimmunity. The maternally derived immunity was durable with the half-life of 14.63 days that reduced the viral replication up to 15 weeks of age. Notably, the passively immunized mice could be actively re-immunized with AdC7-Fsyn to boost and extend the protection. This substantiates maternal immunization with an AdC7-based vaccine expressing RSV F as feasible approach to protect against RSV early in life. PMID:25171847

MEDI4893* Promotes Survival and Extends the Antibiotic Treatment Window in a Staphylococcus aureus Immunocompromised Pneumonia Model.

PubMed

Hua, L; Cohen, T S; Shi, Y; Datta, V; Hilliard, J J; Tkaczyk, C; Suzich, J; Stover, C K; Sellman, B R

2015-08-01

Immunocompromised individuals are at increased risk of Staphylococcus aureus pneumonia. Neutralization of alpha-toxin (AT) with the monoclonal antibody (MAb) MEDI4893* protects normal mice from S. aureus pneumonia; however, the effects of the MAb in immunocompromised mice have not been reported. In this study, passive immunization with MEDI4893* increased survival rates and reduced bacterial numbers in the lungs in an immunocompromised murine S. aureus pneumonia model. Lungs from infected mice exhibited alveolar epithelial damage, protein leakage, and bacterial overgrowth, whereas lungs from mice passively immunized with MEDI4893* retained a healthy architecture, with an intact epithelial barrier. Adjunctive therapy or prophylaxis with a subtherapeutic MEDI4893* dose combined with subtherapeutic doses of vancomycin or linezolid improved survival rates, compared with the monotherapies. Furthermore, coadministration of MEDI4893* with vancomycin or linezolid extended the antibiotic treatment window. These data suggest that MAb-mediated neutralization of AT holds promise in strategies for prevention and adjunctive therapy among immunocompromised patients. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

[Effects of incubation temperature on the results of passive hemagglutination test].

PubMed

Gorchakov, Iu L

1993-01-01

Passive hemagglutination test was carried out at several incubation temperatures: 4, 21, 37, and 56 degrees C. Blood sera of donors, salmonellosis enteritidis patients, and specific nonadsorbed sera were used in the study. The least fluctuations of the results were seen in tests with the sera with the least manifest immune properties. The optimal incubation temperatures were found 4 and 21 degrees C, and in 1/3 of cases cold incubation was found preferable. The relationship between antibody titers and incubation temperature may be described by the formula: T4 > or = T21 > or = T37 > or = T56, with Tn representing the reverse value of antibody titer in certain incubation temperature.

Protection of mice deficient in mature B cells from West Nile virus infection by passive and active immunization

PubMed Central

Draves, Kevin E.; Young, Lucy B.; Bryan, Marianne A.; Dresch, Christiane; Diamond, Michael S.; Gale, Michael

2017-01-01

B cell activating factor receptor (BAFFR)-/- mice have a profound reduction in mature B cells, but unlike μMT mice, they have normal numbers of newly formed, immature B cells. Using a West Nile virus (WNV) challenge model that requires antibodies (Abs) for protection, we found that unlike wild-type (WT) mice, BAFFR-/- mice were highly susceptible to WNV and succumbed to infection within 8 to 12 days after subcutaneous virus challenge. Although mature B cells were required to protect against lethal infection, infected BAFFR-/- mice had reduced WNV E-specific IgG responses and neutralizing Abs. Passive transfer of immune sera from previously infected WT mice rescued BAFFR-/- and fully B cell-deficient μMT mice, but unlike μMT mice that died around 30 days post-infection, BAFFR-/- mice survived, developed WNV-specific IgG Abs and overcame a second WNV challenge. Remarkably, protective immunity could be induced in mature B cell-deficient mice. Administration of a WNV E-anti-CD180 conjugate vaccine 30 days prior to WNV infection induced Ab responses that protected against lethal infection in BAFFR-/- mice but not in μMT mice. Thus, the immature B cells present in BAFFR-/- and not μMT mice contribute to protective antiviral immunity. A CD180-based vaccine may promote immunity in immunocompromised individuals. PMID:29176765

USSR and Eastern Europe Scientific Abstracts, Biomedical and Behavioral Sciences, Number 82

DTIC Science & Technology

1977-12-01

a relatively brief survey of Soviet treatment of burn patients with immune preparations. Infectious complications are said to be the most frequent... treatment . Complications are best treated by the ASP and ASGG type of passive immunization; this treatment can also be employed prophylactically...transmissions and broadcasts. Materials from foreign-language sources are translated; those from English-language sources are transcribed or

The effect of passive immunization against ghrelin on feed and water intake in turkeys.

PubMed

Vizcarra, J A; Wright, H; Vizcarra, A

2012-09-01

Five-week-old turkeys were used to evaluate the effect of passive immunization against ghrelin on feed and water intake and animal behavior. In experiment 1, females were reared using normal feeding and lighting management recommended by the industry. At 5 wk of age (d 0 of experiment 1), birds (n = 40) were individually caged (0.65 × 0.4 × 0.4 m) with free access to feed and water. Feed and water intake were measured 3 times a day (0800, 1200, and 1700 h) by recording the weight of feed or water offered minus any unconsumed feed or water remaining. After 3 d of adaptation to the cages (d 3), birds were stratified by BW and feed consumption and randomly assigned to a 2 × 5 factorial arrangement of treatment. Starting on d 3, turkeys were given intravenous (iv) injections (0.5, 1.0, 2.0, 4.0, or 8.0 mL) of pooled undiluted plasma obtained from pigs that were previously actively immunized against ghrelin or iv injections (0.5, 1.0, 2.0, 4.0, or 8.0 mL) of pooled undiluted plasma, obtained from nonimmunized pigs (control). In experiment 2, the 2 highest doses (i.e., 4.0 and 8.0 mL; n = 4/treatment) were repeated in a 2 × 2 factorial arrangement as described in experiment 1. A laptop computer with a built-in color camera and appropriate software was used to record birds for 9 consecutive hours, starting 4 h before treatments were applied. Video clips were saved and a human observer watched and annotated bird behavior associated with feeding, drinking, and standing. Passively immunized birds increased feed consumption (P = 0.04) compared with control animals. Water intake was not affected by treatments. There was a tendency for immunized birds to increase the number of pecks per hour and the amount of time devoted for feeding. Our data suggest that in turkeys, the effect of immunization against ghrelin on feed intake is the opposite of that observed in mammalian species.

Antibody blocks acquisition of bacterial colonization through agglutination

PubMed Central

Roche, A. M.; Richard, A. L.; Rahkola, J. T.; Janoff, E. N.; Weiser, J. N.

2014-01-01

Invasive infection often begins with asymptomatic colonization of mucosal surfaces. A murine model of bacterial colonization with Streptococcus pneumoniae was used to study the mechanism for mucosal protection by immunoglobulin. In previously colonized immune mice, bacteria were rapidly sequestered within large aggregates in the nasal lumen. To further examine the role of bacterial agglutination in protection by specific antibodies, mice were passively immunized with IgG purified from anti-pneumococcal sera or pneumococcal type-specific monoclonal human IgA (hIgA1 or hIgA2). Systemically-delivered IgG accessed the mucosal surface and blocked acquisition of colonization and transmission between littermates. Optimal protection by IgG was independent of Fc fragment and complement and, therefore, did not involve an opsonophagocytic mechanism. Enzymatic digestion or reduction of IgG prior to administration showed that protection required divalent binding that maintained its agglutinating effect. Divalent hIgA1 is cleaved by the pneumococcal member of a family of bacterial proteases that generate monovalent Fabα fragments. Thus, passive immunization with hIgA1 blocked colonization by an IgA1-protease deficient mutant (agglutinated), but not the protease-producing wild-type parent (not agglutinated), whereas protease-resistant hIgA2 agglutinated and blocked colonization by both. Our findings highlight the importance of agglutinating antibodies in mucosal defense and reveal how successful pathogens evade this effect. PMID:24962092

C 60 fullerene localization and membrane interactions in RAW 264.7 immortalized mouse macrophages

DOE Office of Scientific and Technical Information (OSTI.GOV)

Russ, K. A.; Elvati, P.; Parsonage, T. L.

There continues to be a significant increase in the number and complexity of hydrophobic nanomaterials that are engineered for a variety of commercial purposes making human exposure a significant health concern. This study uses a combination of biophysical, biochemical and computational methods to probe potential mechanisms for uptake of C 60 nanoparticles into various compartments of living immune cells. Cultures of RAW 264.7 immortalized murine macrophage were used as a canonical model of immune-competent cells that are likely to provide the first line of defense following inhalation. Modes of entry studied were endocytosis/pinocytosis and passive permeation of cellular membranes. Themore » evidence suggests marginal uptake of C 60 clusters is achieved through endocytosis/pinocytosis, and that passive diffusion into membranes provides a significant source of biologically-available nanomaterial. Compu-tational modeling of both a single molecule and a small cluster of fullerenes predicts that low concentrations of fullerenes enter the membrane individually and produce limited perturbation; however, at higher concentrations the clusters in the membrane causes deformation of the membrane. These findings are bolstered by nuclear magnetic resonance (NMR) of model membranes that reveal defor-mation of the cell membrane upon exposure to high concentrations of fullerenes. The atomistic and NMR models fail to explain escape of the particle out of biological membranes, but are limited to idealized systems that do not completely recapitulate the complexity of cell membranes. Lastly, the surprising contribution of passive modes of cellular entry provides new avenues for toxicological research that go beyond the pharmacological inhibition of bulk transport systems such as pinocytosis.« less

C 60 fullerene localization and membrane interactions in RAW 264.7 immortalized mouse macrophages

DOE PAGES

Russ, K. A.; Elvati, P.; Parsonage, T. L.; ...

2016-01-01

There continues to be a significant increase in the number and complexity of hydrophobic nanomaterials that are engineered for a variety of commercial purposes making human exposure a significant health concern. This study uses a combination of biophysical, biochemical and computational methods to probe potential mechanisms for uptake of C 60 nanoparticles into various compartments of living immune cells. Cultures of RAW 264.7 immortalized murine macrophage were used as a canonical model of immune-competent cells that are likely to provide the first line of defense following inhalation. Modes of entry studied were endocytosis/pinocytosis and passive permeation of cellular membranes. Themore » evidence suggests marginal uptake of C 60 clusters is achieved through endocytosis/pinocytosis, and that passive diffusion into membranes provides a significant source of biologically-available nanomaterial. Compu-tational modeling of both a single molecule and a small cluster of fullerenes predicts that low concentrations of fullerenes enter the membrane individually and produce limited perturbation; however, at higher concentrations the clusters in the membrane causes deformation of the membrane. These findings are bolstered by nuclear magnetic resonance (NMR) of model membranes that reveal defor-mation of the cell membrane upon exposure to high concentrations of fullerenes. The atomistic and NMR models fail to explain escape of the particle out of biological membranes, but are limited to idealized systems that do not completely recapitulate the complexity of cell membranes. Lastly, the surprising contribution of passive modes of cellular entry provides new avenues for toxicological research that go beyond the pharmacological inhibition of bulk transport systems such as pinocytosis.« less

Prospective cohort study to assess rates of contagious disease in pre-weaned UK dairy heifers: management practices, passive transfer of immunity and associated calf health

PubMed Central

Johnson, Kate F; Chancellor, Natalie; Burn, Charlotte C; Wathes, D Claire

2017-01-01

Dairy calves are vulnerable to infectious diseases, particularly diarrhoea and bovine respiratory disease (BRD), causing mortality and reducing welfare and growth. A prospective cohort study was performed on 11 UK dairy farms to determine the underlying causes for calf disease. This first paper describes the incidence, timing and duration of infectious disease, mortality rates, passive transfer of immunity and key management practices that may contribute to disease incidence. Heifer calves were recruited in the first week of life (n=492) and a blood sample taken to measure IgG and total protein (TP). Each animal was examined weekly for nine weeks using a standardised health scoring system. Recruitment of calves occurred between August and February. Four farms provided supplementary colostrum to more than 75 per cent of calves born, whereas on the remainder only 0 to 19 per cent were supplemented. Mean serum IgG and TP were 19.0±10 and 56.7±10.3 mg/ml respectively, with 20.7 per cent (95CI: 17.2 to 24.7 per cent) of all calves classified as having failure of passive transfer (IgG <10 mg/ml). The overall preweaning mortality rate was 4.5 per cent. (95 per cent CI: 2.9 to 6.8 per cent). During this period,48.2 per cent of all calves (range 24.1 to 74.4 per cent between farms) were diagnosed with diarrhoea and 45.9 per cent (range 20.4 to 77.8 per cent) with BRD. The incidence rates were 7.8 cases of diarrhoea and 10.1 cases of BRD per 100 calf weeks at risk, respectively. Rates of infectious disease were therefore high despite relatively good passive transfer. PMID:29259784

Acupuncture inhibits the decrease in brain catecholamine contents and the impairment of passive avoidance task in ovariectomized mice.

PubMed

Toriizuka, K; Okumura, M; Iijima, K; Haruyama, K; Cyong, J C

1999-01-01

The effects of acupuncture on the disorders elicited by abnormalities of endocrine system were investigated in ovariectomized mice. Female mice (strain; C57BL/6) were ovariectomized (OVX) and acupuncture points, Shenshu ([Japanese pictograph see text] : BL23) on both side of the back were continuously stimulated by subcutaneous needles for 20 days. After completion of experimental sessions, animals were sacrificed and specific brain regions were assayed for catecholamine contents by high performance liquid chromatography with electro chemical detector (ECD-HPLC). The mitogenic activities of splenic lymphocytes were measured by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTS) assay and alkaline phosphatase (ALP) assay. Furthermore, the effects of needle stimulation on learning and memory ability were studied by the step-through type passive avoidance test. Norepinephrine and dopamine contents in the frontoparietal cerebral cortex, ventral hippocampus and olfactory bulb were decreased in the OVX group, and both MTS activity and ALP activity were decreased 20 days after ovariectomy. The mean latent period was also shortened in the passive avoidance test in the OVX group. However, applying needle stimulation increased norepinephrine and dopamine contents in the brain regions, and enhanced mitogenic activities of splenic lymphocytes. The stimulation also improved memory-related behavior. It was concluded from this study that after mice were stimulated by subcutaneous needle insertion, overall changes were observed in central nervous system (including retention of memory) and immune functions. The study suggests that acupuncture improves the memory loss and decrease of immune responses accompanying aging and/or menopause, and the that it may have an important role in medical care for the elderly.

In vivo protection against ZIKV infection and pathogenesis through passive antibody transfer and active immunisation with a prMEnv DNA vaccine.

PubMed

Muthumani, Karuppiah; Griffin, Bryan D; Agarwal, Sangya; Kudchodkar, Sagar B; Reuschel, Emma L; Choi, Hyeree; Kraynyak, Kimberly A; Duperret, Elizabeth K; Keaton, Amelia Anne; Chung, Christopher; Kim, Yinho K; Booth, Stephanie A; Racine, Trina; Yan, Jian; Morrow, Matthew P; Jiang, Jingjing; Lee, Brian; Ramos, Stephanie; Broderick, Kate E; Reed, Charles C; Khan, Amir S; Humeau, Laurent; Ugen, Kenneth E; Park, Young K; Maslow, Joel N; Sardesai, Niranjan Y; Joseph Kim, J; Kobinger, Gary P; Weiner, David B

2016-01-01

Significant concerns have been raised owing to the rapid global spread of infection and disease caused by the mosquito-borne Zika virus (ZIKV). Recent studies suggest that ZIKV can also be transmitted sexually, further increasing the exposure risk for this virus. Associated with this spread is a dramatic increase in cases of microcephaly and additional congenital abnormalities in infants of ZIKV-infected mothers, as well as a rise in the occurrence of Guillain Barre' syndrome in infected adults. Importantly, there are no licensed therapies or vaccines against ZIKV infection. In this study, we generate and evaluate the in vivo efficacy of a novel, synthetic, DNA vaccine targeting the pre-membrane+envelope proteins (prME) of ZIKV. Following initial in vitro development and evaluation studies of the plasmid construct, mice and non-human primates were immunised with this prME DNA-based immunogen through electroporation-mediated enhanced DNA delivery. Vaccinated animals were found to generate antigen-specific cellular and humoral immunity and neutralisation activity. In mice lacking receptors for interferon (IFN)-α/β (designated IFNAR -/- ) immunisation with this DNA vaccine induced, following in vivo viral challenge, 100% protection against infection-associated weight loss or death in addition to preventing viral pathology in brain tissue. In addition, passive transfer of non-human primate anti-ZIKV immune serum protected IFNAR -/- mice against subsequent viral challenge. This study in NHP and in a pathogenic mouse model supports the importance of immune responses targeting prME in ZIKV infection and suggests that additional research on this vaccine approach may have relevance for ZIKV control and disease prevention in humans.

In vivo protection against ZIKV infection and pathogenesis through passive antibody transfer and active immunisation with a prMEnv DNA vaccine

PubMed Central

Muthumani, Karuppiah; Griffin, Bryan D; Agarwal, Sangya; Kudchodkar, Sagar B; Reuschel, Emma L; Choi, Hyeree; Kraynyak, Kimberly A; Duperret, Elizabeth K; Keaton, Amelia Anne; Chung, Christopher; Kim, Yinho K; Booth, Stephanie A; Racine, Trina; Yan, Jian; Morrow, Matthew P; Jiang, Jingjing; Lee, Brian; Ramos, Stephanie; Broderick, Kate E; Reed, Charles C; Khan, Amir S; Humeau, Laurent; Ugen, Kenneth E; Park, Young K; Maslow, Joel N; Sardesai, Niranjan Y; Joseph Kim, J; Kobinger, Gary P; Weiner, David B

2016-01-01

Significant concerns have been raised owing to the rapid global spread of infection and disease caused by the mosquito-borne Zika virus (ZIKV). Recent studies suggest that ZIKV can also be transmitted sexually, further increasing the exposure risk for this virus. Associated with this spread is a dramatic increase in cases of microcephaly and additional congenital abnormalities in infants of ZIKV-infected mothers, as well as a rise in the occurrence of Guillain Barre’ syndrome in infected adults. Importantly, there are no licensed therapies or vaccines against ZIKV infection. In this study, we generate and evaluate the in vivo efficacy of a novel, synthetic, DNA vaccine targeting the pre-membrane+envelope proteins (prME) of ZIKV. Following initial in vitro development and evaluation studies of the plasmid construct, mice and non-human primates were immunised with this prME DNA-based immunogen through electroporation-mediated enhanced DNA delivery. Vaccinated animals were found to generate antigen-specific cellular and humoral immunity and neutralisation activity. In mice lacking receptors for interferon (IFN)-α/β (designated IFNAR−/−) immunisation with this DNA vaccine induced, following in vivo viral challenge, 100% protection against infection-associated weight loss or death in addition to preventing viral pathology in brain tissue. In addition, passive transfer of non-human primate anti-ZIKV immune serum protected IFNAR−/− mice against subsequent viral challenge. This study in NHP and in a pathogenic mouse model supports the importance of immune responses targeting prME in ZIKV infection and suggests that additional research on this vaccine approach may have relevance for ZIKV control and disease prevention in humans. PMID:29263859

Immunization to Protect the U.S. Armed Forces: Heritage, Current Practice, Prospects

DTIC Science & Technology

2005-01-01

population . (4, 12, 16, 163, 164) This vaccine was derived from virus- infected mouse brain. Immunization to Protect the U.S. Armed Forces 14...individual health and to keep units strong so they can accomplish their military missions. The FDA-licensed vaccines selected protect against infections ...CA. Passive protection of mice against lethal Francisella tularensis (live tularemia vaccine strain) infection by the sera of human recipients of

Immunologic memory response induced by a meningococcal serogroup C conjugate vaccine using the P64k recombinant protein as carrier.

PubMed

Guirola, María; Urquiza, Dioslaida; Alvarez, Anabel; Cannan-Haden, Leonardo; Caballero, Evelin; Guillén, Gerardo

2006-03-01

In this study, we used an adoptive lymphocyte transfer experiment to evaluate the ability of the P64k recombinant protein to recruit T-helper activity and induce immunologic memory response to the polysaccharide moiety in a meningococcal serogroup C conjugate vaccine. Adoptive transfer of splenocytes from mice immunized with the glycoconjugate conferred antipolysaccharide immunologic memory to naive recipient mice. The observed anamnestic immune response was characterized by more rapid kinetics, isotype switching from IgM to IgG and higher antipolysaccharide antibody titers compared with those reached in groups transferred with splenocytes from plain polysaccharide or phosphate-immunized mice. The memory response generated was also long lasting. Sera from mice transferred with cells from conjugate-immunized mice were the only protective in the infant rat passive protection assay, and also showed higher bactericidal titers. We demonstrated that priming the mice immune system with the glycoconjugate using the P64k protein as carrier induced a memory response to the polysaccharide, promoting a switch of the T-cell-independent response to a T-cell dependent one.

Water system virus detection

NASA Technical Reports Server (NTRS)

Fraser, A. S.; Wells, A. F.; Tenoso, H. J. (Inventor)

1978-01-01

The performance of a waste water reclamation system is monitored by introducing a non-pathogenic marker virus, bacteriophage F2, into the waste-water prior to treatment and, thereafter, testing the reclaimed water for the presence of the marker virus. A test sample is first concentrated by absorbing any marker virus onto a cellulose acetate filter in the presence of a trivalent cation at low pH and then flushing the filter with a limited quantity of a glycine buffer solution to desorb any marker virus present on the filter. Photo-optical detection of indirect passive immune agglutination by polystyrene beads indicates the performance of the water reclamation system in removing the marker virus. A closed system provides for concentrating any marker virus, initiating and monitoring the passive immune agglutination reaction, and then flushing the system to prepare for another sample.

MEMS reagent and sample handling procedure: Feasibility of viral antibody detection by passive immune agglutination

NASA Technical Reports Server (NTRS)

Bailey, G. D.; Tenoso, H. J.

1975-01-01

An attempt was made to develop a test requiring no preadsorption steps for the assessment of antibodies to rubella and mumps viruses using the passive immune agglutination (PIA) method. Both rubella and mumps antigens and antibodies were prepared. Direct PIA tests, using rubella antigen-coated beads, and indirect PIA tests, using rubella antibody-coated beads, were investigated. Attempts, using either method, were unsuccessful. Serum interference along with nonspecific agglutination of beads by the rubella antigen resulted in no specific response under the test conditions investigated. A new, highly sensitive approach, the enzyme immunoassay (EIA) test system, is recommended to overcome the nonspecificity. This system is a logical outgrowth of some of the solid phase work done on MEMS and represents the next generation tests system that can be directly applied to early disease detection and monitoring.

Passive transfer of growth-inhibitory antibodies raised against yeast-expressed recombinant Plasmodium falciparum merozoite surface protein-1(19).

PubMed

Gozalo, A; Lucas, C; Cachay, M; Wellde, B T; Hall, T; Bell, B; Wood, J; Watts, D; Wooster, M; Lyon, J A; Moch, J K; Haynes, J D; Williams, J S; Holland, C; Watson, E; Kester, K E; Kaslow, D C; Ballou, W R

1998-12-01

Purified rabbit immunoglobulin raised against yeast-expressed recombinant FVO or 3D7 Plasmodium falciparum merozoite surface protein-1 (MSP-1) 19k-D C terminal fragment (MSP-1(19)) was transfused into malaria-naive Aotus nancymai monkeys that were immediately challenged with FVO asexual stage malaria parasites. Control monkeys received rabbit immunoglobulin raised against the sexual stage antigen Pfs25 or Aotus hyperimmune serum obtained from monkeys immunized by P. falciparum infection and drug cure. Passive transfer of rabbit anti-MSP-1(19) failed to protect against homologous or heterologous challenge and, when compared with negative controls, there were no differences in prepatent periods or time to treatment. Interestingly, rabbit anti-MSP-1(19), but not anti-Pfs25, immunoglobulin, and immune monkey serum prevented the development of antibodies directed against MSP-1(19) fragment by infected monkeys, indicating that the antibodies were reactive with native MSP-1(19) antigen in vivo. The prepatent period and time to treatment was greatly delayed in the two monkeys that received Aotus immune serum, both of which developed a chronic intermittent low level infection. In vitro parasite growth inhibition assays (GIAs) confirmed the presence of inhibitory activity (40% maximum inhibition) in concentrated anti-MSP-1(19) immunoglobulin (4.8 mg/ml), but the peak concentrations we achieved in vivo (1 mg/ml) were not inhibitory in vitro. Subinhibitory levels of anti-MSP-1(19) antibodies achieved by passive transfer were not protective against P. falciparum challenge.

Effects of newborn characteristics and length of colostrum feeding period on passive immune transfer in goat kids.

PubMed

Castro, N; Capote, J; Morales-Delanuez, A; Rodríguez, C; Argüello, A

2009-04-01

Majorera goat kids (n = 200) were used to evaluate the effects of litter size, birth body weight, sex, and suckling duration on serum IgG concentrations. Kids were assigned to 1 of 3 experimental groups: litter size and sex were equally distributed in each group. In the first group, kids (n = 67) stayed with their dams for 24 h; in the second group, kids (n = 66) stayed with their dams for 48 h; and in the third group, kids (n = 67) stayed with their dams for 120 h. Blood samples were obtained every 24 h for 5 d, and serum IgG concentration was measured using radial immunodiffusion. In litter sizes of 1 to 2 kids, IgG blood serum concentration was significantly higher (18.30 +/- 5.40 mg/mL) than in litters of 3 kids (9.85 +/- 4.23 mg/mL). Kid sex did not affect IgG blood serum concentrations. Suckling duration did not affect kid serum IgG concentrations. In conclusion, kids with low birth body weight (<2.8 kg) or from litters of 3 may need special attention. If newborn goat kids are allowed to suckle colostrum for at least 24 h from their dams, this seems to be sufficient time to ingest enough IgG from colostrum to achieve an adequate serum IgG concentration and passive immune protection to avoid failure of passive immune transfer.

No effects of acclimation to heat on immune and hormonal responses to passive heating in healthy volunteers

NASA Astrophysics Data System (ADS)

Kanikowska, Dominika; Sato, Maki; Sugenoya, Junichi; Iwase, Satoshi; Shimizu, Yuuki; Nishimura, Naoki; Inukai, Yoko

2012-01-01

Heat acclimation results in whole body-adaptations that increase heat tolerance, and might also result in changed immune responses. We hypothesized that, after heat acclimation, tumor necrosis factor alpha, interleukin 6 and the lymphocyte count would be altered. Heat acclimation was induced in 6 healthy men by 100 min of heat exposure for 9 days. Heat exposure consisted of (1) 10 min of immersion up to chest-level in water at 42°C and (2) 90 min of passive heating by a warm blanket to maintain tympanic temperature at 37.5°C. The climatic chamber was maintained at 40°C and a relative humidity of 50%. Blood samples were analyzed before and after heat acclimation for natural killer (NK) cell activity, counts of lymphocytes B and T, before and after heat acclimation for peripheral blood morphology, interleukin 6, tumor necrosis factor alpha, and cortisol. A Japanese version of the profile of mood states questionnaire was also administered before and after acclimation. The concentrations of white blood cells, lymphocytes B and T, cortisol, interleukin 6, tumor necrosis factor alpha and NK cell activity showed no significant differences between pre- and post-acclimation, but there was a significantly lower platelet count after acclimation and, with the profile of mood states questionnaire, there was a significant rise in anger after acclimation. It is concluded that heat acclimation by passive heating does not induce alterations in immune or endocrine responses.

Transcutaneous immunization with tetanus toxoid and mutants of Escherichia coli heat-labile enterotoxin as adjuvants elicits strong protective antibody responses.

PubMed

Tierney, Rob; Beignon, Anne-Sophie; Rappuoli, Rino; Muller, Sylviane; Sesardic, Dorothea; Partidos, Charalambos D

2003-09-01

In this study, the adjuvanticity of 2 nontoxic derivatives (LTK63 and LTR72) of heat-labile enterotoxin of Escherichia coli (LT) was evaluated and was compared with that of a cytosine phosphodiester-guanine (CpG) motif, after transcutaneous immunization with tetanus toxoid (TT). TT plus LTR72 elicited the strongest antibody responses, compared with those elicited by the other vaccines (TT, TT plus LTK63, TT plus CpG, and TT plus LTK63 plus CpG); it neutralized the toxin and conferred full protection after passive transfer in mice. Preexisting immunity to LT mutants did not adversely affect their adjuvant potency. Both LTK63 and LTR72 promoted the induction of IgG1 antibodies. In contrast, mice receiving either CpG motif alone or CpG motif plus LTK63 produced strong IgG2a anti-TT antibody responses. Overall, these findings demonstrate that mutants of enterotoxins with reduced toxicity are effective adjuvants for transcutaneous immunization.

Human milk oligosaccharides: The role in the fine-tuning of innate immune responses.

PubMed

Kulinich, Anna; Liu, Li

2016-09-02

In order to secure the health of newborns over the period of immune immaturity during the first months of life, a mother provides her offspring with passive protection: bioactive molecules transferred through the placenta and breast milk. It is well known that human milk contains immunoglobulins (Ig), immune cells and diverse cytokines, which affect newborn directly or indirectly and contribute to the maturation of the immune system. However, in addition to the above-stated molecules, human milk oligosaccharides (HMOs), a complex mixture of free indigestible carbohydrates with multiple functions, play exceptional roles in the functioning of the infants' immune system. These biological molecules have been studied over decades, however, interest in HMOs does not seem to have abated. Although biological activities of oligosaccharides from human milk have been explicitly reviewed, information regarding the role of HMOs in inflammation remains rather fragmented. The purpose of this review is to compile existing knowledge about the role of certain species of HMOs, including fucosylated, galactosylated and sialylated oligosaccharides, and their signaling pathways in immunity and inflammation. The advances in applying this information to the treatment of diseases in infants as well as adults were also reviewed here. Copyright © 2016 Elsevier Ltd. All rights reserved.

Characterization of allergoids from ovalbumin in vitro and in vivo.

PubMed

Salgado, J; Casadevall, G; Puigneró, V; Queralt, J

1996-01-01

Several in vivo and in vitro methods for monitoring immunological properties of two allergoids obtained by formaldehyde treatment of ovalbumin (OA) were developed. The calculated molecular weight of allergoids was 80 kD (OA-F1) and 165 kD (OA-F2), respectively. The allergenic activity in vitro of allergoids in mast-cell histamine release assay was 1000 times lower than of OA. Both allergoids showed reduced ability to induce passive cutaneous anaphylaxis in the Sprague-Dawley rats or systemic anaphylaxis in Dunkin-Harley guinea-pigs. The ability of OA and allergoids to bind to the OA-specific IgE antibodies was measured in vivo by the inhibition of passive cutaneous anaphylaxis (PCA-inhibition). Allergoid binding to IgE was 51-66% lower than the native allergen. Moreover, the avidity of OA-specific IgG antibodies, measured by ELISA-inhibition, for allergoids and allergen was of the same order. Allergoids induced a different pattern of humoral immune response from that, induced by the native allergen. Thus, after immunization of BALB/c mouse, both allergoids induced a higher production of IgG and a lower production of IgE than OA, only OA-F2 induced a lower production of IgG1. The differences in the IgA response to the immunogens was not significant. Delayed hypersensitivity studies in the BALB/c mouse showed that allergoids were 5- to 12-times less effective in inducing a cell-mediated immune response than OA. The present study provides a battery of immunological methods for preclinical testing of modified allergens.

Lactation-Based Maternal Educational Immunity Crosses MHC Class I Barriers and Can Impart Th1 Immunity to Th2-Biased Recipients

PubMed Central

Ghosh, Mrinal K.; Muller, H. Konrad

2017-01-01

We have previously demonstrated lactational transfer of T cell–based immunity from dam to foster pup. In the short term, a significant part of transferred immunity is passive cellular immunity. However, as time progresses, this is replaced by what we have described as maternal educational immunity such that by young adulthood, all immune cells responding to a foster dam immunogen are the product of the foster pup’s thymus. To reduce confounding factors, this original demonstration used congenic/syngeneic dam and foster pup pairs. In this study, we investigated lactational transfer of immunity to Mycobacterium tuberculosis in MHC class I–mismatched animals, as well as from Th1-biased dams to Th2-biased foster pups. Using immunized C57BL/6J dams, lactational transfer to nonimmunized BALB/cJ foster pups resulted in much greater immunity than direct immunization in 5-wk-old pups (ex vivo assay of pup splenocytes). At this age, 82% of immunogen-responding cells in the pup spleen were produced through maternal educational immunity. FVB/NJ nonimmunized foster recipients had a greater number of maternal cells in the spleen and thymus but a much larger percentage was Foxp3+, resulting in equivalent immunity to direct immunization. Depletion of maternal Foxp3+ cells from pup splenocytes illustrated a substantial role for lactationally transferred dam regulatory T cells in suppression of the ex vivo response in FVB/NJ, but not BALB/cJ, recipients. We conclude that lactational transfer of immunity can cross MHC class I barriers and that Th1 immunity can be imparted to Th2-biased offspring; in some instances, it can be greater than that achieved by direct immunization. PMID:28747348

Adverse events following yellow fever immunization: Report and analysis of 67 neurological cases in Brazil.

PubMed

Martins, Reinaldo de Menezes; Pavão, Ana Luiza Braz; de Oliveira, Patrícia Mouta Nunes; dos Santos, Paulo Roberto Gomes; Carvalho, Sandra Maria D; Mohrdieck, Renate; Fernandes, Alexandre Ribeiro; Sato, Helena Keico; de Figueiredo, Patricia Mandali; von Doellinger, Vanessa Dos Reis; Leal, Maria da Luz Fernandes; Homma, Akira; Maia, Maria de Lourdes S

2014-11-20

Neurological adverse events following administration of the 17DD substrain of yellow fever vaccine (YEL-AND) in the Brazilian population are described and analyzed. Based on information obtained from the National Immunization Program through passive surveillance or intensified passive surveillance, from 2007 to 2012, descriptive analysis, national and regional rates of YFV associated neurotropic, neurological autoimmune disease, and reporting rate ratios with their respective 95% confidence intervals were calculated for first time vaccinees stratified on age and year. Sixty-seven neurological cases were found, with the highest rate of neurological adverse events in the age group from 5 to 9 years (2.66 per 100,000 vaccine doses in Rio Grande do Sul state, and 0.83 per 100,000 doses in national analysis). Two cases had a combination of neurotropic and autoimmune features. This is the largest sample of YEL-AND already analyzed. Rates are similar to other recent studies, but on this study the age group from 5 to 9 years of age had the highest risk. As neurological adverse events have in general a good prognosis, they should not contraindicate the use of yellow fever vaccine in face of risk of infection by yellow fever virus. Copyright © 2014 Elsevier Ltd. All rights reserved.

Moderate summer heat stress does not modify immunological parameters of Holstein dairy cows

NASA Astrophysics Data System (ADS)

Lacetera, Nicola; Bernabucci, Umberto; Ronchi, Bruno; Scalia, Daniela; Nardone, Alessandro

2002-02-01

The study was undertaken during spring and summer months in a territory representative of the Mediterranean climate to assess the effects of season on some immunological parameters of dairy cows. Twenty Holstein cows were used. Eleven of those cows gave birth during spring; the remaining nine cows gave birth in summer. The two groups of cows were homogeneous for parity. Values of air temperatures and relative humidity were recorded both during spring and summer, and were utilized to calculate the temperature humidity index (THI). One week before the expected calving, rectal temperatures and respiratory rates of the cows were recorded (1500 hours), and cell-mediated immunity was assessed by measuring the proliferation of mitogen-stimulated peripheral blood mononuclear cells (PBMC). Within 3 h of calving, one colostrum sample was taken from each cow and analysed to determine content of immunoglobulin (Ig) G1, IgG2, IgM and IgA. At 48 h after birth, passive immunization of the calves was assessed by measuring total serum IgG. During summer, daytime (0900-2000 hours) THI values were above the upper critical value of 72 [75.2, (SD 2.6)] indicating conditions that could represent moderate heat stress. That THI values were able to predict heat stress was confirmed by the values of rectal temperatures and respiratory rates, which were higher ( P < 0.05 and P < 0.001 respectively) during summer. Proliferation of PBMC, the colostral concentration of Ig fractions and serum levels of IgG in their respective offspring did not differ between spring and summer cows. Results indicated that moderate heat stress due to the hot Mediterranean summer does not modify cell-mediated immunity, the protective value of colostrum and passive immunization of the offspring in dairy cows.

Reproductive Fecundity of Iraqi Awassi Ewes Immunized against Synthetic Inhibin-α Subunit or Steroid-Free Bovine Follicular Fluid.

PubMed

Al-Saaidi, Jabbar Abbas Ahmed; Khudair, Khalisa Khadim; Al-Kafaji, Sura Safe Aubaes

2018-03-02

The present study was conducted to investigate the impacts of active and passive immunization against synthetic inhibin and steroid-free bovine follicular fluid, respectively, on reproductive fecundity out of breeding season in Iraqi Awassi ewes. Follicular fluid was aspired from mature bovine follicles, treated with activated charcoal, and used for immunization of male rabbits for obtaining steroid free bovine follicular fluid (SFBFF) antiserum. Forty non-pregnant Awassi ewes were allocated into 4 groups (n = 10 each). At day 38 of experiment, ewes were treated with intra-vaginal MPA sponge (60 mg for 12 days). Ewes were treated at 0, 28, and 50 days with 4, 2 and 2 ml of normal saline (control; C-ve), 400, 200 and 200 µl of ovalbumine (C+ve), 400, 200 and 200 µl of inhibin (SI group), and 4 ml of normal saline at 0 day, and 4ml and 2ml of SFBFF antiserum, at 28, and 50 days (AI group). After mating with Awassi rams, pregnancy and embryo number were diagnosed using ultrasonography. Blood samples were collected at 30, 60, 90, and 120 days of pregnancy, for assessment of estradiol-17β (E2) and progesterone (P4) levels. After parturition, numbers of delivered lambs were recorded. The results revealed significant increase of P4 and significant decrease of E2 levels in SI and AI pregnant ewes than controls at 30, 60 and 90 day. Newborn number increased significantly in SI and AI treated than control ewes. Active or passive immunization against endogenous inhibin could augment reproductive fecundity out of breeding season in Iraqi Awassi ewes.

Effect of intravenous plasma transfusion on granulocyte and monocyte oxidative and phagocytic activity in dairy calves with failure of passive immunity.

PubMed

Yang, Victoria C; Rayburn, Maire C; Chigerwe, Munashe

2017-12-01

Plasma administration has been recommended in calves older than 48h with failure of passive immunity (FPI) to provide immunity consistent with adequate colostral ingestion. However, the protective serum immunoglobulin G (IgG) concentrations (≥1000mg/dL) of plasma derived IgG only lasts up to 12h. In addition to IgG, maternally derived colostral cells also confer immunity. The objective of the study was to determine the effect of intravenous plasma transfusion on granulocyte and monocyte oxidative and phagocytic activity in calves with FPI. Twenty-seven, one day-old, Jersey calves were assigned into 3 groups. The colostral (CL, N=9) group received 3L of colostrum once by oroesophageal tubing. Two other groups of calves received 1L of colostrum once by oroesophageal tubing and were assigned based on their health status (sick or non-sick) at 4days of age, as the sick-group (SG, N=7) or the non-sick (NG, N=11) groups. At 4days of age, the SG and NG groups were administered plasma intravenously at 30mL/kg. Granulocyte and monocyte oxidative and phagocytic activity was determined by flow cytometry. There was no significant difference in the granulocyte and monocyte oxidative or phagocytic activity among the 3 groups (P>0.05). Plasma administration had no significant effect on the oxidative or phagocytic activity of granulocytes or monocytes. In clinical practice, plasma administration for enhancing oxidative or phagocytic activity of granulocytes or monocytes, alone, might not be justified in calves with FPI. Copyright © 2017 Elsevier Ltd. All rights reserved.

A Modified Surface Killing Assay (MSKA) as a Functional in vitro Assay for Identifying Protective Antibodies Against Pneumococcal Surface Protein A (PspA)

PubMed Central

Genschmer, Kristopher R.; Accavitti-Loper, Mary Ann; Briles, David E.

2013-01-01

Streptococcus pneumoniae causes otitis media, meningitis and pneumonia in patients worldwide; predominantly affecting young children, the elderly, and the immune compromised. Current vaccines against invasive pneumococcal disease are based on the polysaccharide capsules of the most clinically relevant serotypes. Due to serotype replacement, non-vaccine serotypes of S. pneumoniae have become more clinically relevant and as a result pneumococcal vaccines are becoming increasingly complex. These events emphasize the need to evaluate the potential for pneumococcal cross-reactive proteins to contribute to future vaccines. Antibody elicited by the immunization of humans with pneumococcal surface protein A (PspA) can passively protect mice from infection. However, robust in vitro functional assays for antibody to PspA are not available to predict the protective capacity of immune serum. For polysaccharide based vaccines, a standardized opsonophagocytosis killing assay (OPKA) is used. Antibody to PspA, however, does not work well in the standard OPKA. The present studies take advantage of past observations that phagocytosis is more efficient on tissue surfaces than in solution. In a modified surface killing assay (MSKA), monoclonal antibody to PspA, in the presence of complement, opsonized pneumococci for killing by phagocytes on an agar surface. Five monoclonal antibodies to PspA were tested; three demonstrated increased amounts of killing compared to the diluent control and protected mice by passive protection against type 3 pneumococci. The two antibodies that were not functional in the MSKA also failed to protect mice. Thus, an MSKA might be useful as a functional assay for immunity to PspA. PMID:24211169

Maternal antibodies protect offspring from severe influenza infection and do not lead to detectable interference with subsequent offspring immunization.

PubMed

van der Lubbe, Joan E M; Vreugdenhil, Jessica; Damman, Sarra; Vaneman, Joost; Klap, Jaco; Goudsmit, Jaap; Radošević, Katarina; Roozendaal, Ramon

2017-06-26

Various studies have shown that infants under the age of 6 months are especially vulnerable for complications due to influenza. Currently there are no vaccines licensed for use in this age group. Vaccination of pregnant women during the last trimester, recommended by the WHO as protective measure for this vulnerable female population, may provide protection of newborns at this early age. Although it has been observed that maternal vaccination can passively transfer protection, maternal antibodies could possibly also interfere with subsequent active vaccination of the offspring. Using a mouse model, we evaluated in depth the ability of maternal influenza vaccination to protect offspring and the effect of maternal immunization on the subsequent influenza vaccination of the offspring. By varying the regimen of maternal immunization we explored the impact of different levels of maternal antibodies on the longevity of these antibodies in their progeny. We subsequently assessed to what extent maternal antibodies can mediate direct protection against influenza in their offspring, and whether these antibodies interfere with protection induced by active vaccination of the offspring. The number of immunizations of pregnant mice correlates to the level and longevity of maternal antibodies in the offspring. When these antibodies are present at time of influenza challenge they protect offspring against lethal influenza challenge, even in the absence of detectable HAI titers. Moreover, no detectable interference of passively-transferred maternal antibodies on the subsequent vaccination of the offspring was observed. In the absence of a licensed influenza vaccine for young children, vaccination of pregnant women is a promising measure to provide protection of young infants against severe influenza infection.

Immunotherapy for Infectious Diseases: Past, Present, and Future.

PubMed

Manohar, Akshay; Ahuja, Jasmine; Crane, John K

2015-01-01

Passive immunotherapy for established infections, as opposed to active immunization to prevent disease, remains a tiny niche in the world of antimicrobial therapies. Many of the passive immunotherapies currently available are directed against bacterial toxins, such as botulism, or are intended for agents of bioterrorism such as anthrax, which fortunately has remained rare. The emergence of Ebola virus and multi-drug resistant pathogens, however, may breathe new life into the immunotherapy field as researchers seek non-antibiotic interventions for infectious diseases.

Immunoprophylactic effect of chicken egg yolk antibody (IgY) against a recombinant S1 domain of the porcine epidemic diarrhea virus spike protein in piglets.

PubMed

Lee, Do Hyun; Jeon, Young-Soo; Park, Choi-Kyu; Kim, Seungjoon; Lee, Du Sik; Lee, Changhee

2015-09-01

Porcine epidemic diarrhea virus (PEDV) is a highly contagious enteric pathogen of swine causing high mortality rates in piglets. PEDV outbreaks have occurred continuously in most swine-producing Asian countries and have recently emerged in the United States, leading to large economic losses for both the Asian and US pig industries. The spike (S) protein of PEDV consists of the S1 and S2 domains, responsible for virus binding and fusion, respectively. The involvement of the S1 domain in specific high-affinity interactions with the cellular receptor and induction of neutralizing antibodies in the natural host makes it a logical target for the development of effective vaccines and therapeutics against PEDV. Passive immunization by oral administration of egg yolk antibodies (IgY) obtained from immunized chickens provides an alternative source of specific antibodies for the prevention and treatment of PEDV in newborn piglets. In this study, we produced an IgY against the PEDV S1 protein and investigated its immunoprophylactic effect in neonatal piglets. A codon-optimized PEDV S1 gene consisting of amino acid residues 25-749 was synthesized and used to establish a stable porcine cell line constitutively expressing a recombinant PEDV S1 protein containing the chicken immunoglobulin Fc fragment at its C-terminus. The purified recombinant S1 protein was found to mediate potent immune responses in immunized hens. We next tested the ability of oral passive immunization with anti-PEDV S1 IgY to protect piglets against PEDV. Specific chicken IgY against the S1 protein was orally administered to neonatal piglets, and their responses subsequent to a virulent PEDV challenge were monitored. The results showed that oral administration of anti-PEDV S1 IgY efficiently protects neonatal piglets against PEDV, suggesting its potential as a prophylactic or therapeutic agent against acute PEDV infection.

The piglet as a model for B cell and immune system development

PubMed Central

Butler, J.E.; Lager, K.M.; Splichal, I.; Francis, D.; Kacskovics, I.; Sinkora, M.; Wertz, N.; Sun, J.; Zhao, Y.; Brown, W.R.; DeWald, R.; Dierks, S.; Muyldermans, S.; Lunney, J.K.; McCray, P.B.; Rogers, C.S.; Welsh, M.J.; Navarro, P.; Klobasa, F.; Habe, F.; Ramsoondar, J.

2010-01-01

The ability to identify factors responsible for disease in all species depends on the ability to separate those factors which are environmental from those that are intrinsic. This is particularly important for studies on the development of the adaptive immune response of neonates. Studies on laboratory rodents or primates have been ambiguous because neither the effect of environmental nor maternal factors on the newborn can be controlled in mammals that: (i) transmit potential maternal immunoregulatory factors in utero and (ii) are altricial and cannot be reared after birth without their mothers. Employing the newborn piglet model can address each of these concerns. However, it comes at the price of having first to characterize the immune system of swine and its development. This review focuses on the porcine B cell system, especially on the methods used for its characterization in fetal studies and neonatal piglets. Understanding these procedures is important in the interpretation of the data obtained. Studies on neonatal piglets have (a) provided valuable information on the development of the adaptive immune system, (b) lead to important advances in evolutionary biology, (c) aided our understanding of passive immunity and (d) provided opportunities to use swine to address specific issues in veterinary and biomedical research and immunotherapy. This review summarizes the history of the development of the piglet as a model for antibody repertoire development, thus providing a framework to guide future investigators. PMID:19056129

Intravenous immunoglobulin and Alzheimer's disease immunotherapy.

PubMed

Solomon, Beka

2007-02-01

Amyloid-beta peptide (Abeta) contributes to the acute progression of Alzheimer's disease (AD) and has become the main target for therapeutics. Active immunization with Abeta in individuals with AD has been efficacious; however, some patients developed side effects, possibly related to an autoimmune response. Evidence that intravenous immunoglobulin (IVIg), an FDA-approved purified immunoglobulin fraction from normal human donor blood, shows promise of passive immunotherapy for AD is reviewed. Investigations into the molecular effects of IVIg on Abeta clearance, using the BV-2 cellular microglia line, demonstrate that IVIg dissolves Abeta fibrils in vitro, increases cellular tolerance to Abeta, enhances microglial migration toward Abeta deposits, and mediates phagocytosis of Abeta. Preliminary clinical results indicate that IVIg, which contains natural antibodies against the Abeta, warrants further study into its potential to deliver a controlled immune attack on the peptide, avoiding the immune toxicities that have had a negative impact on the first clinical trials of vaccine against Abeta.

Evaluation of the effects of colostrum replacer supplementation of the milk replacer ration on the occurrence of disease, antibiotic therapy, and performance of pre-weaned dairy calves.

PubMed

Chamorro, Manuel F; Cernicchiaro, Natalia; Haines, Deborah M

2017-02-01

The objective of this study was to evaluate the effects of colostrum supplementation of the milk replacer ration on disease occurrence, antibiotic therapy, and performance of pre-weaned dairy calves with adequate transfer of passive immunity. Two hundred and two 1-d-old Holstein dairy calves were assigned to 1 of 2 groups after arrival to a dairy calf rearing facility. Calves assigned to the control group (n = 100) received milk replacer (28% crude protein and 20% crude fat) without colostrum inclusion twice daily. Calves assigned to the treatment group (n = 102) received 150 g of supplemental colostrum replacer powder added to their milk replacer twice daily for the first 14 d of life. Before group assignment, serum samples were collected from all calves to confirm transfer of passive immunity. Calves were evaluated daily until weaning (56 d of life) for signs of clinical disease as well as any treatment with antibiotics. Presentation of clinical disease and antibiotic treatment was recorded daily by personnel blinded to treatment allocation. Adequate transfer of passive immunity was confirmed in all calves at the start of the study and mean serum IgG values were similar among calves from treatment and control groups. The odds ratios of having abnormal feces and abnormal respiration during the pre-weaning period for calves from the treatment group were 0.15 and 0.46 the odds ratios of calves from the control group, respectively. The odds ratios of receiving antibiotic therapy during the pre-weaning period for calves from the treatment group were 0.09 the odds ratios of calves from the control group. Mean body weight and average daily gain at weaning were not significantly different among calves from the treatment and control groups. Colostrum replacer supplementation of the milk replacer ration was effective in reducing antibiotic therapy and occurrence of disease during the pre-weaning period. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

PEGylation of Vesicular Stomatitis Virus Extends Virus Persistence in Blood Circulation of Passively Immunized Mice

PubMed Central

Tesfay, Mulu Z.; Kirk, Amber C.; Hadac, Elizabeth M.; Griesmann, Guy E.; Federspiel, Mark J.; Barber, Glen N.; Henry, Stephen M.; Peng, Kah-Whye

2013-01-01

We are developing oncolytic vesicular stomatitis viruses (VSVs) for systemic treatment of multiple myeloma, an incurable malignancy of antibody-secreting plasma cells that are specifically localized in the bone marrow. One of the presumed advantages for using VSV as an oncolytic virus is that human infections are rare and preexisting anti-VSV immunity is typically lacking in cancer patients, which is very important for clinical success. However, our studies show that nonimmune human and mouse serum can neutralize clinical-grade VSV, reducing the titer by up to 4 log units in 60 min. In addition, we show that neutralizing anti-VSV antibodies negate the antitumor efficacy of VSV, a concern for repeat VSV administration. We have investigated the potential use of covalent modification of VSV with polyethylene glycol (PEG) or a function-spacer-lipid (FSL)–PEG construct to inhibit serum neutralization and to limit hepatosplenic sequestration of systemically delivered VSV. We report that in mice passively immunized with neutralizing anti-VSV antibodies, PEGylation of VSV improved the persistence of VSV in the blood circulation, maintaining a more than 1-log-unit increase in VSV genome copies for up to 1 h compared to the genome copy numbers for the non-PEGylated virus, which was mostly cleared within 10 min after intravenous injection. We are currently investigating if this increase in PEGylated VSV circulating half-life can translate to increased virus delivery and better efficacy in mouse models of multiple myeloma. PMID:23325695

Maternal immunization with respiratory syncytial virus fusion protein formulated with a novel combination adjuvant provides protection from RSV in newborn lambs.

PubMed

Garg, R; Latimer, L; Wang, Y; Simko, E; Gerdts, V; Potter, A; van Drunen Littel-van den Hurk, S

2016-01-04

Respiratory syncytial virus (RSV) is the causative agent of serious upper and lower respiratory tract infections in newborns and infants. Protection from RSV is crucial for neonates, and maternal immunization is one approach that holds promise for providing immediate protection to young infants against severe RSV infection. We previously reported efficacy of a subunit vaccine consisting of the fusion (F) protein formulated with a novel adjuvant (ΔF/TriAdj) in neonates. The goal of the current study was to evaluate the ΔF/TriAdj as a maternal vaccine. Pregnant ewes were vaccinated intramuscularly with ΔF/TriAdj or PBS six weeks prior to lambing, and re-vaccinated four weeks later, which resulted in transfer of maternal antibodies (MatAbs) to the newborn lambs through the colostrum. Significantly higher levels of RSV ΔF-specific serum IgG were detected in vaccinated pregnant ewes and their lambs when compared to control animals, which revealed that MatAbs were passively transferred to the offspring. All newborn lambs were challenged with RSV at three days of age. After RSV challenge, virus production and lung pathology were significantly lower in lambs that had received passively transferred antibodies than in control animals. These results indicate that maternal immunization with ΔF/TriAdj might be an alternative, safe and effective approach to provide protection against RSV in newborn and young infants. Copyright © 2015 Elsevier Ltd. All rights reserved.

Immunization with recombinant V10 protects cynomolgus macaques from lethal pneumonic plague.

PubMed

Cornelius, Claire A; Quenee, Lauriane E; Overheim, Katie A; Koster, Frederick; Brasel, Trevor L; Elli, Derek; Ciletti, Nancy A; Schneewind, Olaf

2008-12-01

Vaccine and therapeutic strategies that prevent infections with Yersinia pestis have been sought for over a century. Immunization with live attenuated (nonpigmented) strains and immunization with subunit vaccines containing recombinant low-calcium-response V antigen (rLcrV) and recombinant F1 (rF1) antigens are considered effective in animal models. Current antiplague subunit vaccines in development for utilization in humans contain both antigens, either as equal concentrations of the two components (rF1 plus rLcrV) or as a fusion protein (rF1-rLcrV). Here, we show that immunization with either purified rLcrV (a protein at the tip of type III needles) or a variant of this protein, recombinant V10 (rV10) (lacking amino acid residues 271 to 300), alone or in combination with rF1, prevented pneumonic lesions and disease pathogenesis. In addition, passive immunization studies showed that specific antibodies of macaques immunized with rLcrV, rV10, or rF1, either alone or in combination, conferred protection against bubonic plague challenge in mice. Finally, we found that when we compared the reactivities of anti-rLcrV and anti-rV10 immune sera from cynomolgus macaques, BALB/c mice, and brown Norway rats with LcrV-derived peptides, rV10, but not rLcrV immune sera, lacked antibodies recognizing linear LcrV oligopeptides.

Eosinophils mediate protective immunity against secondary nematode infection.

PubMed

Huang, Lu; Gebreselassie, Nebiat G; Gagliardo, Lucille F; Ruyechan, Maura C; Luber, Kierstin L; Lee, Nancy A; Lee, James J; Appleton, Judith A

2015-01-01

Eosinophils are versatile cells that regulate innate and adaptive immunity, influence metabolism and tissue repair, and contribute to allergic lung disease. Within the context of immunity to parasitic worm infections, eosinophils are prominent yet highly varied in function. We have shown previously that when mice undergo primary infection with the parasitic nematode Trichinella spiralis, eosinophils play an important immune regulatory role that promotes larval growth and survival in skeletal muscle. In this study, we aimed to address the function of eosinophils in secondary infection with T. spiralis. By infecting eosinophil-ablated mice, we found that eosinophils are dispensable for immunity that clears adult worms or controls fecundity in secondary infection. In contrast, eosinophil ablation had a pronounced effect on secondary infection of skeletal muscle by migratory newborn larvae. Restoring eosinophils to previously infected, ablated mice caused them to limit muscle larvae burdens. Passive immunization of naive, ablated mice with sera or Ig from infected donors, together with transfer of eosinophils, served to limit the number of newborn larvae that migrated in tissue and colonized skeletal muscle. Results from these in vivo studies are consistent with earlier findings that eosinophils bind to larvae in the presence of Abs in vitro. Although our previous findings showed that eosinophils protect the parasite in primary infection, these new data show that eosinophils protect the host in secondary infection. Copyright © 2014 by The American Association of Immunologists, Inc.

Antibody transferred from the blood to the gastrointestinal tract and its role in enteric immunity of neonatal calves

DOE Office of Scientific and Technical Information (OSTI.GOV)

Besser, T.E.

1986-01-01

High passive blood immunoglobulin concentrations are associated with decreased infectious enteric disease mortality in neonatal calves. Passive immunoglobulin transferred from the blood to the gastrointestinal tract may explain this protection. To measure the rate at which immunoglobulin G/sub 1/ (IgG/sub 1/) is transferred to the gastrointestinal tract, /sup 125/I-labelled bovine IgG/sub 1/ anti-DNP antibody was administered to calves by intravenous injection. The clearance rate of /sup 125/I-IgG/sub 1/ from the blood was measured and compared to the rate of /sup 125/I-IgG/sub 1/ appearance in the gastrointestinal tract, as measured (1) by the rate of fecal /sup 125/I-IgG/sub 1/ excretion, andmore » (2) by the amount of /sup 125/I-IgG/sub 1/ in the gastrointestinal tract of calves at necropsy. Rotavirus antibody titers in the gastrointestinal contents of 5- and 10-days-old calves correlated with the calves' serum passive rotavirus antibody titers, and were increased in proportion to the amount of colostral antibody fed on the first day of life. In contrast, when colostral rotavirus antibody was fed to 48-hour-old calves, when absorption of passive immunoglobulin does not occur, there was no measurable increase in antibody in the intestine 5 days later. Intestinal antibody in the 5- and 10-day-old calves therefore resulted from blood antibody transferred to the gastrointestinal tract. Rotavirus antibody administered to calves by parenteral injection protected them from infection and diarrhea after rotavirus challenge. These results indicate that passive blood IgG enters the calf gastrointestinal tract, where it contributes to intestinal immunity.« less

Immune transfer studies in canine allogeneic marrow graft donor-recipient pairs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grosse-Wilde, H.; Krumbacher, K.; Schuening, F.D.

1986-07-01

Transfer of immunity occurring with bone marrow grafting was studied using the dog as a preclinical model. Allogeneic bone marrow transplantation (BMT) was performed between DLA-identical beagle litter-mates. The donors were immunized with tetanus toxoid (TT) or sheep red blood cells (SRBC), and their humoral response was monitored by hemagglutination. The recipients of bone marrow from TT-immunized donors showed a marked increase of antibody titer one week posttransplantation, while in the recipients of marrow from SRBC immunized donors the antibody titers were considerably lower. Within the following 60 days the antibody titers in both groups diminished gradually to pregrafting levels.more » Control experiments in which cell-free plasma from donors immunized with TT and SRBC respectively was transfused indicated that the initial rise of specific antibody titers after marrow grafting is likely to be due to a passive transfer of humoral immunity. A single challenge of these marrow graft recipients with the respective antigen 15-18 weeks posttransplantation led to a secondary type of humoral immune response. It could be demonstrated that transfer of memory against TT or SRBC was independent from the actual antibody titer and the time of vaccination of the donor. One dog was immunized with TT after serving as marrow donor. When the donor had shown an antibody response, a peripheral blood leukocytes (PBL) transfusion was given to his chimera. Subsequent challenge of the latter resulted in a secondary type of specific antibody response. This indicates that specific cellular-bound immunological memory can be transferred after BMT from the donor to his allogeneic bone marrow chimera by transfusion of peripheral blood leukocytes. The data may be of importance in clinical BMT to protect patients during the phase of reduced immune reactivity by transfer of memory cells.« less

Systematic Review and Meta-Analysis of Diagnostic Accuracy of Serum Refractometry and Brix Refractometry for the Diagnosis of Inadequate Transfer of Passive Immunity in Calves.

PubMed

Buczinski, S; Gicquel, E; Fecteau, G; Takwoingi, Y; Chigerwe, M; Vandeweerd, J M

2018-01-01

Transfer of passive immunity in calves can be assessed by direct measurement of immunoglobulin G (IgG) by methods such as radial immunodiffusion (RID) or turbidimetric immunoassay (TIA). IgG can also be measured indirectly by methods such as serum refractometry (REF) or Brix refractometry (BRIX). To determine the accuracy of REF and BRIX for assessment of inadequate transfer of passive immunity (ITPI) in calves. Systematic review and meta-analysis of diagnostic accuracy studies. Databases (PubMed and CAB Abstract, Searchable Proceedings of Animal Science) and Google Scholar were searched for relevant studies. Studies were eligible if the accuracy (sensitivity and specificity) of REF or BRIX was determined using direct measurement of IgG by RID or turbidimetry as the reference standard. The study population included calves <14 days old that were fed with natural colostrum (colostrum replacement products were excluded). Quality assessment was performed by the QUADAS-2 tool. Hierarchical models were used for meta-analysis. From 1,291 references identified, 13 studies of 3,788 calves were included. Of these, 11 studies evaluated REF and 5 studies evaluated BRIX. The median (range) prevalence of ITPI (defined as calves with IgG <10 g/L by RID or TIA) was 21% (1.3-56%). Risk of bias and applicability concerns were generally low or unclear. For REF, summary estimates were obtained for 2 different cutoffs: 5.2 g/dL (6 studies) and 5.5 g/dL (5 studies). For the 5.2 g/dL cutoff, the summary sensitivity (95% CI) and specificity (95% CI) were 76.1% (63.8-85.2%) and 89.3% (82.3-93.7%), and 88.2% (80.2-93.3%) and 77.9% (74.5-81.0%) for the 5.5 g/dL cutoff. Due to the low number of studies using the same cutoffs, summary estimates could not be obtained for BRIX. Despite their widespread use on dairy farms, evidence about the optimal strategy for using refractometry, including the optimal cutoff, are sparse (especially for BRIX). When using REF to rule out ITPI in herds, the 5.5 g/dL cutoff may be used whereas for ruling in ITPI, the 5.2 g/dL cutoff may be used. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Recent progress in immune-based interventions to prevent HIV-1 transmission to children.

PubMed

Voronin, Yegor; Jani, Ilesh; Graham, Barney S; Cunningham, Coleen K; Mofenson, Lynne M; Musoke, Philippa M; Permar, Sallie R; Scarlatti, Gabriella

2017-12-01

Globally, 150,000 new paediatric human immunodeficiency virus type 1 (HIV-1) infections occurred in 2015. There remain complex challenges to the global elimination of paediatric HIV-1 infection. Thus, for the global community to achieve elimination of new paediatric HIV-1 infections, innovative approaches need to be explored. Immune-based approaches to prevention of mother-to-child transmission (MTCT) may help fill some of the remaining gaps and provide new opportunities to achieve an AIDS-free generation. Immune-based interventions to prevent MTCT of HIV-1 may include paediatric HIV vaccines and passive immunization approaches. Recent discoveries providing evidence of robust immune responses to HIV in infants open new and exciting prospects for paediatric HIV vaccines. Moreover, successful vaccination of infants has a different set of requirements than vaccination of adults and may be easier to achieve. Proof-of-concept has been established over the last two decades that passively administered HIV-1 Env-specific monoclonal antibody (mAbs) can prevent chimeric simian human immunodeficiency virus (SHIV) transmission to newborn nonhuman primates. There has been tremendous progress in isolating and characterizing broadly neutralizing antibodies to HIV, and clinical testing of these antibodies for treatment and prevention in both infants and adults is a major effort in the field. Immune-based interventions need to be actively explored as they can provide critically important tools to address persistent challenges in MTCT prevention. It is a pivotal time for the field with active discussions on the best strategy to further reduce HIV infection of infants and accomplish the World Health Organization Fast-Track 2030 goals to eliminate new paediatric HIV infections. © 2017 The Authors. Journal of the International AIDS Society published by John Wiley & sons Ltd on behalf of the International AIDS Society.

Comparative opsonic and protective activities of Staphylococcus aureus conjugate vaccines containing native or deacetylated Staphylococcal Poly-N-acetyl-beta-(1-6)-glucosamine.

PubMed

Maira-Litrán, Tomás; Kropec, Andrea; Goldmann, Donald A; Pier, Gerald B

2005-10-01

Staphylococcus aureus and Staphylococcus epidermidis both synthesize the surface polysaccharide poly-N-acetyl-beta-(1-6)-glucosamine (PNAG), which is produced in vitro with a high level (>90%) of the amino groups substituted by acetate. Here, we examined the role of the acetate substituents of PNAG in generating opsonic and protective antibodies. PNAG and a deacetylated form of the antigen (dPNAG; 15% acetylation) were conjugated to the carrier protein diphtheria toxoid (DT) and used to immunize animals. Mice responded in a dose-dependent fashion to both conjugate vaccines, with maximum antibody titers observed at the highest dose and 4 weeks after the last of three weekly immunizations. PNAG-DT and dPNAG-DT vaccines were also very immunogenic in rabbits. Antibodies raised to the conjugate vaccines in rabbits mediated the opsonic killing of various staphylococcal strains, but the specificity of the opsonic killing was primarily to dPNAG, as this antigen inhibited the killing of S. aureus strains by both PNAG- and dPNAG-specific antibodies. Passive immunization of mice with anti-dPNAG-DT rabbit sera showed significant levels of clearance of S. aureus from the blood (54 to 91%) compared to control mice immunized with normal rabbit sera, whereas PNAG-specific antibodies were ineffective at clearing S. aureus. Passive immunization of mice with a goat antiserum raised to the dPNAG-DT vaccine protected against a lethal dose of three different S. aureus strains. Overall, these data show that immunization of animals with a conjugate vaccine of dPNAG elicit antibodies that mediated opsonic killing and protected against S. aureus infection, including capsular polysaccharide types 5 and 8 and an untypable strain.

Resistance of bovine colostral anti-cholera toxin antibody to in vitro and in vivo proteolysis.

PubMed Central

McClead, R E; Gregory, S A

1984-01-01

Pregnant cows immunized with cholera enterotoxin produce an immunoglobulin G class 1 antibody that enters the colostrum in high titer. After exposure to intestinal enzymes, this antibody remains immunologically reactive and inhibits intestinal fluid secretion in infant and adult rabbits exposed to cholera enterotoxin. Specific bovine colostral antibodies may be a source of passive immune protection for human infants and adults at risk for cholera and other enteric diseases. PMID:6425223

Resistance against Taenia hydatigena in sheep after passive transfer of serum or colostrum.

PubMed

Jacobs, H J; Moriarty, K M; Charleston, W A; Heath, D D

1994-07-01

The role of antibody in the resistance of sheep to infection with Taenia hydatigena metacestodes was examined using passive transfer of immunoglobulin. The immunoglobulin either was experimentally transferred in serum, or was transferred from immune ewes to their new-born lambs in colostrum. Pooled serum from donor lambs which had received one, light, oral infection did not protect recipients although the donors themselves were immune. However, transfer of pooled serum from donors which had either received three oral infections, or three immunizations with solubilized T. hydatigena oncospheres in a water-in-oil adjuvant, resulted in 70-80% fewer cysts in the recipients. Colostrum from ewes infected with three high or low doses of T. hydatigena eggs was transferred to their lambs. A short acting protection (one to three weeks) was observed in the lambs. Comparisons by ELISA and Western blot, of the anti-T. hydatigena oncosphere antibody content of the donor sera, the sera of the recipients collected 24 h and seven days after transfer, the sera of the lambs and ewes, and the colostrum of the ewes, indicated that resistance to the challenge infection depends upon a critical level of antibody.

Diagnostic accuracy of refractometer and Brix refractometer to assess failure of passive transfer in calves: protocol for a systematic review and meta-analysis.

PubMed

Buczinski, S; Fecteau, G; Chigerwe, M; Vandeweerd, J M

2016-06-01

Calves are highly dependent of colostrum (and antibody) intake because they are born agammaglobulinemic. The transfer of passive immunity in calves can be assessed directly by dosing immunoglobulin G (IgG) or by refractometry or Brix refractometry. The latter are easier to perform routinely in the field. This paper presents a protocol for a systematic review meta-analysis to assess the diagnostic accuracy of refractometry or Brix refractometry versus dosage of IgG as a reference standard test. With this review protocol we aim to be able to report refractometer and Brix refractometer accuracy in terms of sensitivity and specificity as well as to quantify the impact of any study characteristic on test accuracy.

Interactions Between Macrophages of Guinea Pigs and Salmonellae III. Bactericidal Action and Cytophilic Antibodies of Macrophages of Infected Guinea Pigs

PubMed Central

Hsu, H. S.; Mayo, Donald R.

1973-01-01

The fate of virulent Salmonella typhimurium within macrophages of guinea pigs was assessed by a suspended cell culture procedure. The present study confirmed that macrophages of normal guinea pigs were capable of inactivating the ingested salmonellae. Macrophages of previously infected guinea pigs were not endowed with any significant increase in their ability to eliminate the ingested pathogen. However, the immune macrophages were observed to clump together tightly when they were exposed to salmonellae. This phenomenon was attributed to the presence of specific cytophilic antibodies on the immune macrophages. When immune macrophages were inactivated with Merthiolate, they agglutinated with both the H and the O antigens of S. typhimurium, but not with the O antigens of other species of Salmonella nor with the O antigens of Escherichia coli. Cytophilic antibodies could be eluted from immune macrophages by incubation in the absence of immune serum. Conversely, cytophilic antibodies could be passively transferred onto normal macrophages by incubation in the presence of immune serum. Furthermore, using immune serum previously adsorbed with the O antigens of S. typhimurium, cytophilic antibodies against the H antigens alone could be transferred onto normal macrophages, or those against the O antigens alone could be eluted from immune macrophages. These data suggest that immune macrophages possess specific cytophilic antibodies against both the H and the O antigens of S. typhimurium. It is proposed that the presence of cytophilic antibodies on immune macrophages represents an expression of antibacterial cellular immunity by enhanced clumping and phagocytic activities of the macrophages. PMID:4579899

Preclinical assessment of safety of maternal vaccination against respiratory syncytial virus (RSV) in cotton rats.

PubMed

Blanco, Jorge C G; Pletneva, Lioubov M; Otoa, Raymonde O; Patel, Mira C; Vogel, Stefanie N; Boukhvalova, Marina S

2017-07-13

Maternal immunization directed to control RSV infection in newborns and infants is an appealing vaccination strategy currently under development. In this work we have modeled maternal vaccination against RSV in cotton rats (CR) to answer two fundamental questions on maternal vaccine safety. We tested (i), whether a known, unsafe RSV vaccine (i.e., FI-RSV Lot 100 vaccine) induces vaccine enhanced disease in the presence of passively transferred, RSV maternal immunity, and (ii) whether the same FI-RSV vaccine could induce vaccine enhanced disease in CR litters when used to immunize their RSV-primed mothers. Our data show that FI-RSV immunization of pups with subsequent RSV infection results in vaccine-enhanced disease independent of whether the pups were born to RSV-seropositive or RSV-seronegative mothers, and that FI-RSV immunization of RSV-seropositive mothers does not present a health risk to either the mother or the infant. Our study also raises a novel concern regarding infant immunization, namely that "safe" RSV vaccines (e.g., live RSV administered intramuscularly) may induce vaccine-enhanced disease in RSV-infected pups born to seropositive mothers. Finally, we describe for the first time a sharp decrease in RSV neutralizing antibody titers in immunized seropositive CR at the time of delivery. This decline may reflect maternal immune suppression, potentially pinpointing a window of increased vulnerability to RSV infection that could be alleviated by effective immunization of expectant mothers. Copyright © 2017 Elsevier Ltd. All rights reserved.

HIV-1 Therapy with Monoclonal Antibody 3BNC117 Elicits Host Immune Responses against HIV-1

PubMed Central

Schoofs, Till; Klein, Florian; Braunschweig, Malte; Kreider, Edward F.; Feldmann, Anna; Nogueira, Lilian; Oliveira, Thiago; Lorenzi, Julio C. C.; Parrish, Erica H.; Learn, Gerald H.; West, Anthony P.; Bjorkman, Pamela J.; Schlesinger, Sarah J.; Seaman, Michael S.; Czartoski, Julie; McElrath, M. Juliana; Pfeifer, Nico; Hahn, Beatrice H.; Caskey, Marina; Nussenzweig, Michel C.

2016-01-01

3BNC117 is a broad and potent anti-HIV-1 neutralizing antibody that targets the CD4 binding site on the viral envelope spike. When administered passively, this antibody can prevent infection in animal models and suppress viremia in HIV-1-infected individuals. Here we report that HIV-1 immunotherapy with a single injection of 3BNC117 impacts host antibody responses in viremic subjects. In comparison to untreated controls that showed little change in their neutralizing activity over a six-month period, 3BNC117 infusion significantly improved neutralizing responses to heterologous tier 2 viruses in nearly all study participants. We conclude that 3BNC117-mediated immunotherapy enhances host humoral immunity to HIV-1. PMID:27199429

IgY Antibodies Protect against Human Rotavirus Induced Diarrhea in the Neonatal Gnotobiotic Piglet Disease Model

PubMed Central

Vega, Celina G.; Bok, Marina; Vlasova, Anastasia N.; Chattha, Kuldeep S.; Fernández, Fernando M.; Wigdorovitz, Andrés; Parreño, Viviana G.; Saif, Linda J.

2012-01-01

Group A Rotaviruses are the most common cause of severe, dehydrating diarrhea in children worldwide. The aim of the present work was to evaluate protection against rotavirus (RV) diarrhea conferred by the prophylactic administration of specific IgY antibodies (Ab) to gnotobiotic piglets experimentally inoculated with virulent Wa G1P[8] human rotavirus (HRV). Chicken egg yolk IgY Ab generated from Wa HRV hyperimmunized hens specifically recognized (ELISA) and neutralized Wa HRV in vitro. Supplementation of the RV Ab free cow milk diet with Wa HRV-specific egg yolk IgY Ab at a final ELISA Ab titer of 4096 (virus neutralization –VN- titer = 256) for 9 days conferred full protection against Wa HRV associated diarrhea and significantly reduced virus shedding. This protection was dose-dependent. The oral administration of semi-purified passive IgY Abs from chickens did not affect the isotype profile of the pig Ab secreting cell (ASC) responses to Wa HRV infection, but it was associated with significantly fewer numbers of HRV–specific IgA ASC in the duodenum. We further analyzed the pigś immune responses to the passive IgY treatment. The oral administration of IgY Abs induced IgG Ab responses to chicken IgY in serum and local IgA and IgG Ab responses to IgY in the intestinal contents of neonatal piglets in a dose dependent manner. To our knowledge, this is the first study to show that IgY Abs administered orally as a milk supplement passively protect neonatal pigs against an enteric viral pathogen (HRV). Piglets are an animal model with a gastrointestinal physiology and an immune system that closely mimic human infants. This strategy can be scaled-up to inexpensively produce large amounts of polyclonal IgY Abs from egg yolks to be applied as a preventive and therapeutic passive Ab treatment to control RV diarrhea. PMID:22880110

Sensing Danger: Key to Activating Plant Immunity.

PubMed

Gust, Andrea A; Pruitt, Rory; Nürnberger, Thorsten

2017-09-01

In both plants and animals, defense against pathogens relies on a complex surveillance system for signs of danger. Danger signals may originate from the infectious agent or from the host itself. Immunogenic plant host factors can be roughly divided into two categories: molecules which are passively released upon cell damage ('classical' damage-associated molecular patterns, DAMPs), and peptides which are processed and/or secreted upon infection to modulate the immune response (phytocytokines). We highlight the ongoing challenge to understand how plants sense various danger signals and integrate this information to produce an appropriate immune response to diverse challenges. Copyright © 2017 Elsevier Ltd. All rights reserved.

Anti-α-synuclein immunotherapy reduces α-synuclein propagation in the axon and degeneration in a combined viral vector and transgenic model of synucleinopathy.

PubMed

Spencer, Brian; Valera, Elvira; Rockenstein, Edward; Overk, Cassia; Mante, Michael; Adame, Anthony; Zago, Wagner; Seubert, Peter; Barbour, Robin; Schenk, Dale; Games, Dora; Rissman, Robert A; Masliah, Eliezer

2017-01-13

Neurodegenerative disorders such as Parkinson's Disease (PD), PD dementia (PDD) and Dementia with Lewy bodies (DLB) are characterized by progressive accumulation of α-synuclein (α-syn) in neurons. Recent studies have proposed that neuron-to-neuron propagation of α-syn plays a role in the pathogenesis of these disorders. We have previously shown that antibodies against the C-terminus of α-syn reduce the intra-neuronal accumulation of α-syn and related deficits in transgenic models of synucleinopathy, probably by abrogating the axonal transport and accumulation of α-syn in in vivo models. Here, we assessed the effect of passive immunization against α-syn in a new mouse model of axonal transport and accumulation of α-syn. For these purpose, non-transgenic, α-syn knock-out and mThy1-α-syn tg (line 61) mice received unilateral intra-cerebral injections with a lentiviral (LV)-α-syn vector construct followed by systemic administration of the monoclonal antibody 1H7 (recognizes amino acids 91-99) or control IgG for 3 months. Cerebral α-syn accumulation and axonopathy was assessed by immunohistochemistry and effects on behavior were assessed by Morris water maze. Unilateral LV-α-syn injection resulted in axonal propagation of α-syn in the contra-lateral site with subsequent behavioral deficits and axonal degeneration. Passive immunization with 1H7 antibody reduced the axonal accumulation of α-syn in the contra-lateral side and ameliorated the behavioral deficits. Together this study supports the notion that immunotherapy might improve the deficits in models of synucleinopathy by reducing the axonal propagation and accumulation of α-syn. This represents a potential new mode of action through which α-syn immunization might work.

Enhanced phagocytic activity of HIV-specific antibodies correlates with natural production of immunoglobulins with skewed affinity for FcγR2a and FcγR2b.

PubMed

Ackerman, Margaret E; Dugast, Anne-Sophie; McAndrew, Elizabeth G; Tsoukas, Stephen; Licht, Anna F; Irvine, Darrell J; Alter, Galit

2013-05-01

While development of an HIV vaccine that can induce neutralizing antibodies remains a priority, decades of research have proven that this is a daunting task. However, accumulating evidence suggests that antibodies with the capacity to harness innate immunity may provide some protection. While significant research has focused on the cytolytic properties of antibodies in acquisition and control, less is known about the role of additional effector functions. In this study, we investigated antibody-dependent phagocytosis of HIV immune complexes, and we observed significant differences in the ability of antibodies from infected subjects to mediate this critical effector function. We observed both quantitative differences in the capacity of antibodies to drive phagocytosis and qualitative differences in their FcγR usage profile. We demonstrate that antibodies from controllers and untreated progressors exhibit increased phagocytic activity, altered Fc domain glycosylation, and skewed interactions with FcγR2a and FcγR2b in both bulk plasma and HIV-specific IgG. While increased phagocytic activity may directly influence immune activation via clearance of inflammatory immune complexes, it is also plausible that Fc receptor usage patterns may regulate the immune response by modulating downstream signals following phagocytosis--driving passive degradation of internalized virus, release of immune modulating cytokines and chemokines, or priming of a more effective adaptive immune response.

Development of recombinant vaccine candidate molecule against Shigella infection.

PubMed

Chitradevi, S T S; Kaur, G; Sivaramakrishna, U; Singh, D; Bansal, A

2016-10-17

Shigellosis is an acute bacillary diarrheal disease caused by the gram negative bacillus Shigella. The existence of multiple Shigella serotypes and their growing resistance to antibiotics stress the urgent need for the development of vaccine that is protective across all serotypes. Shigella's IpaB antigen is involved in translocon pore formation, promotes bacterial invasion and induces apoptosis in macrophages. S. Typhi GroEL (Hsp 60) is the immunodominant antigen inducing both arms of immunity and has been explored as adjuvant in this study. The present study evaluates the immunogenicity and protective efficacy of recombinant IpaB domain-GroEL fusion protein in mice against lethal Shigella infection. The IpaB domain and GroEL genes were fused using overlap extension PCR and cloned in pRSETA expression vector. Fused gene was expressed in Escherichia coli BL-21 cells and the resulting 90 KDa fusion protein was purified by affinity chromatography. Intranasal (i.n.) immunization of mice with fusion protein increased the IgG and IgA antibody titers as compared to the group immunized with IpaB and GroEL and control PBS immunized group. Also IgG1 and IgG2a antibodies induced in fusion protein immunized mice were higher than co-immunized group. Significant increase in lymphocyte proliferation and cytokine levels (IFN-γ, IL-4 and IL-10), indicates induction of both Th1 and Th2 immune responses in both immunized groups. Immunization with fusion protein protected 90-95% of mice whereas 80-85% survivability was observed in co-immunized group against lethal challenge with S. flexneri, S. boydii and S. sonnei. Passive immunization conferred 60-70% protection in mice against all these Shigella species. Organ burden and histopathology studies also revealed significant decrease in lung infection as compared to the co-immunized group. Since IpaB is the conserved dominant molecule in all Shigella species, this study will lead to an ideal platform for the development of safe, efficacious and cost-effective recombinant vaccine against Shigella serotypes. Copyright © 2016 Elsevier Ltd. All rights reserved.

[The effect of active immunization with Acanthamoeba culbertsoni in mice born to immune mother].

PubMed

Kong, H H; Seo, S A; Shin, C O; Im, K I

1993-06-01

Acanthamoeba culbertsoni is a pathogenic free-living amoeba causing primary amoebic meningoencephalitis (PAME) in human and mouse. Several reports on the immune responses in mice with this amoebic infection have been published, but the effects of transferred passive immunity on the active immunization in offspring mice have not been demonstrated. This experiment was done to observe the effect of active immunization with Acanthamoeba culbertsoni in mice born to immune mothers. Acanthamoeba culbertsoni was cultured in the CGV medium axenically. Female BALB/c mice weighing about 20g were immunized through the intraperitoneal injection of Acanthamoeba culbertsoni trophozoites 1 x 10(6) each three times at the interval of one week. Offspring mice were immunized two times. The mice were inoculated intranasally with 1 x 10(4) trophozoites under secobarbital anesthesia. There was a statistical difference in mortality between the transferred immunity group and the active immunization group. Statistical differences were not demonstrated in antibody titer between both groups. But L3T4+ T cell/Ly2+ T cell ratio was increased in the transferred immunity group more than active immunization group of the offspring mice at the age of 5 weeks. There was no differences statistically in mortality between both groups. It was recognized that active immunization in offspring mice born to immune mother could modulate the immune status according to the time of immunization.

CELL SEPARATION ON ANTIGEN-COATED COLUMNS

PubMed Central

Wigzell, Hans; Andersson, Birger

1969-01-01

Glass and plastic bead columns coated with antigenic protein molecules were used as an immunological filter for cell populations containing immune cells of relevant specificity. A selective elimination of these immune cells from the passing cell suspension was regularly noted and it approached, in some experiments, complete abolition of the specific immune reactivity of the filtered cell population. This specific retention of immune cells by antigenic columns could be selectively blocked by the presence of free antigen molecules in the medium during filtration. The results obtained support the concept of a cell-associated antigen-specific receptor being present on the outer surface of immune cells, displaying the same antigen-binding specificity as the potential product of the cell, the humoral antibody. Using the present bead column system, results were obtained indicating that this receptor was an active product of the immune cells and not any passively adsorbed, cytophilic antibody. Antigenic bead columns may very well constitute a tool for the production in vitro of cell populations being specifically deprived of immune reactivity and allow detailed analysis of the characteristics of the cell-associated antibody of immune cells. PMID:5782770

Innate immune system and inflammation in Alzheimer's disease: from pathogenesis to treatment.

PubMed

Serpente, Maria; Bonsi, Rossana; Scarpini, Elio; Galimberti, Daniela

2014-01-01

Immune activation and inflammation, likely triggered by amyloid-beta (Aβ) deposition, play a remarkable role in the pathogenesis of Alzheimer's disease (AD), which is the most frequent cause of dementia in the elderly. The principal cellular elements of the brain innate immune system likely to be involved in such processes are microglia. In an attempt to search for new disease-modifying drugs, the immune system has been addressed, with the aim of removing deposition of Aβ or tau by developing vaccines and humanized monoclonal antibodies. The aim of this review is to summarize the current evidence regarding the role played by microglia and inflammatory molecules in the pathogenesis of AD. In addition, we will discuss the main active and passive immunotherapeutic approaches. © 2014 S. Karger AG, Basel.

Immunity to airborne challenge with Venezuelan equine encephalitis virus develops rapidly after immunization with the attenuated vaccine strain TC-83.

PubMed

Phillpotts, R J

1999-05-14

Mice vaccinated subcutaneously with the attenuated vaccine strain of Venezuelan equine encephalitis virus (VEEV) rapidly develop immunity to subcutaneous or airborne challenge with virulent VEEV. The specificity of this immune response was demonstrated by challenge with a heterologous virus (St. Louis encephalitis virus). Examination of the levels of VEEV-specific antibody classes in serum and respiratory secretions suggested that the rapid development of immunity was coincident with the appearance of specific IgM and IgG (but not IgA) in the respiratory tract. In order to confirm the role of respiratory tract antibody, mice were passively immunised either intraperitoneally or intranasally with polyclonal VEEV-specific IgG. Intranasal administration of specific IgG significantly enhanced protection against airborne challenge. These results confirm the need to emphasise local antibody production in the development of improved VEEV vaccines.

Amyloid-ß-directed immunotherapy for Alzheimer's disease

PubMed Central

Lannfelt, L; Relkin, N R; Siemers, E R

2014-01-01

Lannfelt L, Relkin NR, Siemers ER (Uppsala University, Uppsala, Sweden; Weill Cornell Medical College, New York, NY; and Eli Lilly and Co., Indianapolis, IN, USA). Amyloid-ß-directed immunotherapy for Alzheimer’s disease. (Key Symposium). J Intern Med 2014; 275: 284–295. Current treatment options for Alzheimer's disease (AD) are limited to medications that reduce dementia symptoms. Given the rapidly ageing populations in most areas of the world, new therapeutic interventions for AD are urgently needed. In recent years, a number of drug candidates targeting the amyloid-ß (Aß) peptide have advanced into clinical trials; however, most have failed because of safety issues or lack of efficacy. The Aß peptide is central to the pathogenesis, and immunotherapy against Aß has attracted considerable interest. It offers the possibility to reach the target with highly specific drugs. Active immunization and passive immunization have been the most widely studied approaches to immunotherapy of AD. A favourable aspect of active immunization is the capacity for a small number of vaccinations to generate a prolonged antibody response. A potential disadvantage is the variability in the antibody response across patients. The potential advantages of passive immunotherapy include the reproducible delivery of a known amount of therapeutic antibodies to the patient and rapid clearance of those antibodies if side effects develop. A disadvantage is the requirement for repeated infusions of antibodies over time. After more than a decade of research, anti-amyloid immunotherapy remains one of the most promising emerging strategies for developing disease-modifying treatments for AD. In this review, we examine the presently ongoing Aß-directed immunotherapies that have passed clinical development Phase IIa. PMID:24605809

Biochemical parameters in the blood of Holstein calves given immunoglobulin Y-supplemented colostrums

PubMed Central

2014-01-01

Background In any calf rearing system it is desirable to obtain healthy animals, and reduce morbidity, mortality, and economic losses. Bovine syndesmochorial placentation prevents the direct transfer of bovine immunoglobulins to the fetus, and calves are born hypogammaglobulinemic. These calves therefore require colostrum immediately after birth. Colostrum is rich in immunoglobulins (Ig) and its consumption results in the transfer of passive immunity to calves. The Ig absorption occurs within the first 12 h after birth. Immunoglobulin Y (IgY), derived from chicken egg yolk, has been used in the prevention and control of diseases affecting calves because it is very similar in structure and function to immunoglobulin G (IgG). In the current study, we sought to establish whether administration routes of colostrum supplemented with avian IgY affected passive immunity in calves. Results No significant differences were observed with respect to route of administration for colostrum. However, we did observe some differences in certain interactions between the various treatments. Calves fed colostrum containing egg yolk had higher levels of TP, ALB, and IgG, along with increased GGT activity. Conclusions Our results suggest that supplementing colostrum with egg yolk has a beneficial effect when given to calves, regardless of administration route. PMID:25022282

Immunogenicity and protection in small-animal models with controlled-release tetanus toxoid microparticles as a single-dose vaccine.

PubMed Central

Singh, M; Li, X M; Wang, H; McGee, J P; Zamb, T; Koff, W; Wang, C Y; O'Hagan, D T

1997-01-01

Tetanus toxoid (TT) was encapsulated in microparticles prepared from polylactide-co-glycolide polymers by a solvent-evaporation technique. Combinations of small- and large-sized microparticles with controlled-release characteristics were used to immunize Sprague-Dawley rats, and the antibody responses were monitored for 1 year. For comparison, control groups of rats were immunized at 0, 1, and 2 months with TT adsorbed to alum. The antibody responses generated by the TT entrapped in microparticles were comparable to those generated by TT adsorbed to alum in control groups from 32 weeks onwards. Microparticles with a single entrapped antigen (TT) induced better antibody responses than microparticles with two antigens (TT and diphtheria toxoid) entrapped simultaneously. A combination vaccine consisting of TT adsorbed to alum and also entrapped in microparticles gave the best antibody responses. In an inhibition assay designed to determine the relative levels of binding of antisera to the antigens, the sera from the microparticle- and the alum-immunized animals showed comparable levels of binding. In addition, in a passive-challenge study with mice, TT adsorbed to alum and TT entrapped in microparticles provided equal levels of protection against a lethal challenge with tetanus toxin. An intradermal-challenge study was also performed with rabbits, which showed similar levels of protection in sera from alum- and microparticle-immunized animals at 4, 12, and 32 weeks after immunization. PMID:9125552

2015 Guidance on cancer immunotherapy development in early-phase clinical studies.

PubMed

2015-12-01

The development of cancer immunotherapies is progressing rapidly with a variety of technological approaches. They consist of "cancer vaccines", which are based on the idea of vaccination, "effector cell therapy", classified as passive immunotherapy, and "inhibition of immunosuppression", which intends to break immunological tolerance to autoantigens or immunosuppressive environments characterizing antitumor immune responses. Recent reports showing clinical evidence of efficacy of immune checkpoint inhibitors and adoptive immunotherapies with tumor-infiltrating lymphocytes and tumor-specific receptor gene-modified T cells indicate the beginning of a new era for cancer immunotherapy. This guidance summarizes ideas that will be helpful to those who plan to develop cancer immunotherapy. The aims of this guidance are to discuss and offer important points in early phase clinical studies of innovative cancer immunotherapy, with future progress in this field, and to contribute to the effective development of cancer immunotherapy aligned with the scope of regulatory science. This guidance covers cancer vaccines, effector cell therapy, and inhibition of immunosuppression, including immune checkpoint inhibitors. © 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

Bacterial Toxins—Staphylococcal Enterotoxin B

PubMed Central

FRIES, BETTINA C.; VARSHNEY, AVANISH K.

2015-01-01

Staphylococcal enterotoxin B is one of the most potent bacterial superantigens that exerts profound toxic effects upon the immune system, leading to stimulation of cytokine release and inflammation. It is associated with food poisoning, nonmenstrual toxic shock, atopic dermatitis, asthma, and nasal polyps in humans. Currently, there is no treatment or vaccine available. Passive immunotherapy using monoclonal antibodies made in several different species has shown significant inhibition in in vitro studies and reduction in staphylococcal enterotoxin B-induced lethal shock in in vivo studies. This should encourage future endeavors to develop these antibodies as therapeutic reagents. PMID:26184960

Anti-Pseudomonas aeruginosa IgY antibodies augment bacterial clearance in a murine pneumonia model.

PubMed

Thomsen, K; Christophersen, L; Bjarnsholt, T; Jensen, P Ø; Moser, C; Høiby, N

2016-03-01

Oral prophylactic therapy by gargling with pathogen-specific egg yolk immunoglobulins (IgY) may reduce the initial airway colonization with Pseudomonas aeruginosa in cystic fibrosis (CF) patients. IgY antibodies impart passive immunization and we investigated the effects of anti-P. aeruginosa IgY antibodies on bacterial eradication in a murine pneumonia model. P. aeruginosa pneumonia was established in Balb/c mice and the effects of prophylactic IgY administration on lung bacteriology, clinical parameters and subsequent inflammation were compared to controls. Prophylactic administration of IgY antibodies targeting P. aeruginosa significantly reduced the bacterial burden by 2-log 24h post-infection compared to controls and was accompanied by significantly reduced clinical symptom scores and successive inflammatory cytokine profile indicative of diminished lung inflammation. Passive immunization by anti-P. aeruginosa IgY therapy facilitates promptly bacterial clearance and moderates inflammation in P. aeruginosa lung infection and may serve as an adjunct to antibiotics in reducing early colonization. Copyright © 2015. Published by Elsevier B.V.

PEGylated graphene oxide elicits strong immunological responses despite surface passivation

NASA Astrophysics Data System (ADS)

Luo, Nana; Weber, Jeffrey K.; Wang, Shuang; Luan, Binquan; Yue, Hua; Xi, Xiaobo; Du, Jing; Yang, Zaixing; Wei, Wei; Zhou, Ruhong; Ma, Guanghui

2017-02-01

Engineered nanomaterials promise to transform medicine at the bio-nano interface. However, it is important to elucidate how synthetic nanomaterials interact with critical biological systems before such products can be safely utilized in humans. Past evidence suggests that polyethylene glycol-functionalized (PEGylated) nanomaterials are largely biocompatible and elicit less dramatic immune responses than their pristine counterparts. We here report results that contradict these findings. We find that PEGylated graphene oxide nanosheets (nGO-PEGs) stimulate potent cytokine responses in peritoneal macrophages, despite not being internalized. Atomistic molecular dynamics simulations support a mechanism by which nGO-PEGs preferentially adsorb onto and/or partially insert into cell membranes, thereby amplifying interactions with stimulatory surface receptors. Further experiments demonstrate that nGO-PEG indeed provokes cytokine secretion by enhancing integrin β8-related signalling pathways. The present results inform that surface passivation does not always prevent immunological reactions to 2D nanomaterials but also suggest applications for PEGylated nanomaterials wherein immune stimulation is desired.

Unusual loss of chymosin in mammalian lineages parallels neo-natal immune transfer strategies.

PubMed

Lopes-Marques, Mónica; Ruivo, Raquel; Fonseca, Elza; Teixeira, Ana; Castro, L Filipe C

2017-11-01

Gene duplication and loss are powerful drivers of evolutionary change. The role of loss in phenotypic diversification is notably illustrated by the variable enzymatic repertoire involved in vertebrate protein digestion. Among these we find the pepsin family of aspartic proteinases, including chymosin (Cmy). Previous studies demonstrated that Cmy, a neo-natal digestive pepsin, is inactivated in some primates, including humans. This pseudogenization event was hypothesized to result from the acquisition of maternal immune immunoglobulin G (IgG) transfer. By investigating 94 mammalian subgenomes we reveal an unprecedented level of Cmy erosion in placental mammals, with numerous independent events of gene loss taking place in Primates, Dermoptera, Rodentia, Cetacea and Perissodactyla. Our findings strongly suggest that the recurrent inactivation of Cmy correlates with the evolution of the passive transfer of IgG and uncovers a noteworthy case of evolutionary cross-talk between the digestive and the immune system, modulated by gene loss. Copyright © 2017 Elsevier Inc. All rights reserved.

Colostrum proinflammatory cytokines as biomarkers of bovine immune response to bovine tuberculosis (bTB).

PubMed

Sánchez-Soto, Eduardo; Ponce-Ramos, Rosa; Hernández-Gutiérrez, Rodolfo; Gutiérrez-Ortega, Abel; Álvarez, Angel H; Martínez-Velázquez, Moisés; Absalón, Angel E; Ortiz-Lazareno, Pablo; Limón-Flores, Alberto; Estrada-Chávez, Ciro; Herrera-Rodríguez, Sara E

2017-02-01

Bovine colostrum contains compounds, which provide passive immune protection from mother to newborn calves. Little is known about cytokine levels and their role in bovine colostrum. Moreover, the capacity of bovine colostrum cells to mount specific immune responses after natural exposure to bovine tuberculosis (bTB) antigens in dairy herds has not been studied, thus far. The purpose of this study was to identify biomarkers for bTB infection measurable in bovine colostrum. The present study reveals that isolated-immune colostrum cells can mount a specific immune response against bTB antigens, by measuring the novo IFN-γ release in cell culture. We found that IFN-γ levels in the responders (Bov + ) to bTB antigen were higher than in non-responders (Bov - ). On the other hand, proinflammatory cytokines contained in colostrum's whey were tested in Tuberculin Skin Test (TST) reactor (TST + ) and non-reactor (TST - ) animals to assess their potential role as biomarker. We observed that IFN-γ levels were lower or undetectable, as opposed to IL4 levels were measurable, the TNF-α level was higher in TST - than TST + , while IL-6 levels showed the opposite reaction and with no statistical significance. Moreover, IL-1α mRNA expression levels were higher in colostrum mononuclear cells (CMC) in Bov + cattle. Collectively, these data suggest that the differential expression of pro and anti-inflammatory cytokines could have relevant value to diagnose bTB in cattle. Copyright © 2016 Elsevier Ltd. All rights reserved.

Vectored Intracerebral Immunization with the Anti-Tau Monoclonal Antibody PHF1 Markedly Reduces Tau Pathology in Mutant Tau Transgenic Mice.

PubMed

Liu, Wencheng; Zhao, Lingzhi; Blackman, Brittany; Parmar, Mayur; Wong, Man Ying; Woo, Thomas; Yu, Fangmin; Chiuchiolo, Maria J; Sondhi, Dolan; Kaminsky, Stephen M; Crystal, Ronald G; Paul, Steven M

2016-12-07

Passive immunization with anti-tau monoclonal antibodies has been shown by several laboratories to reduce age-dependent tau pathology and neurodegeneration in mutant tau transgenic mice. These studies have used repeated high weekly doses of various tau antibodies administered systemically for several months and have reported reduced tau pathology of ∼40-50% in various brain regions. Here we show that direct intrahippocampal administration of the adeno-associated virus (AAV)-vectored anti-phospho-tau antibody PHF1 to P301S tau transgenic mice results in high and durable antibody expression, primarily in neurons. Hippocampal antibody levels achieved after AAV delivery were ∼50-fold more than those reported following repeated systemic administration. In contrast to systemic passive immunization, we observed markedly reduced (≥80-90%) hippocampal insoluble pathological tau species and neurofibrillary tangles following a single dose of AAV-vectored PHF1 compared with mice treated with an AAV-IgG control vector. Moreover, the hippocampal atrophy observed in untreated P301S mice was fully rescued by treatment with the AAV-vectored PHF1 antibody. Vectored passive immunotherapy with an anti-tau monoclonal antibody may represent a viable therapeutic strategy for treating or preventing such tauopathies as frontotemporal dementia, progressive supranuclear palsy, or Alzheimer's disease. We have used an adeno-associated viral (AAV) vector to deliver the genes encoding an anti-phospho-tau monoclonal antibody, PHF1, directly to the brain of mice that develop neurodegeneration due to a tau mutation that causes frontotemporal dementia (FTD). When administered systemically, PHF1 has been shown to modestly reduce tau pathology and neurodegeneration. Since such antibodies do not readily cross the blood-brain barrier, we used an AAV vector to deliver antibody directly to the hippocampus and observed much higher antibody levels and a much greater reduction in tau pathology. Using AAV vectors to deliver antibodies like PHF1 directly to brain may constitute a novel approach to treating various neurodegenerative disorders, such as FTD and Alzheimer's disease. Copyright © 2016 the authors 0270-6474/16/3612425-11$15.00/0.

Pulmonary immunization of chickens using non-adjuvanted spray-freeze dried whole inactivated virus vaccine completely protects against highly pathogenic H5N1 avian influenza virus.

PubMed

Peeters, Ben; Tonnis, Wouter F; Murugappan, Senthil; Rottier, Peter; Koch, Guus; Frijlink, Henderik W; Huckriede, Anke; Hinrichs, Wouter L J

2014-11-12

Highly pathogenic avian influenza (HPAI) H5N1 virus is a major threat to public health as well as to the global poultry industry. Most fatal human infections are caused by contact with infected poultry. Therefore, preventing the virus from entering the poultry population is a priority. This is, however, problematic in emergency situations, e.g. during outbreaks in poultry, as there are currently no mass application methods to effectively vaccinate large numbers of birds within a short period of time. To evaluate the suitability of needle-free pulmonary immunization for mass vaccination of poultry against HPAI H5N1, we performed a proof-of-concept study in which we investigated whether non-adjuvanted spray-freeze-dried (SFD) whole inactivated virus (WIV) can be used as a dry powder aerosol vaccine to immunize chickens. Our results show that chickens that received SFD-WIV vaccine as aerosolized powder directly at the syrinx (the site of the tracheal bifurcation), mounted a protective antibody response after two vaccinations and survived a lethal challenge with HPAI H5N1. Furthermore, both the number of animals that shed challenge virus, as well as the level of virus shedding, were significantly reduced. Based on antibody levels and reduction of virus shedding, pulmonary vaccination with non-adjuvanted vaccine was at least as efficient as intratracheal vaccination using live virus. Animals that received aerosolized SFD-WIV vaccine by temporary passive inhalation showed partial protection (22% survival) and a delay in time-to-death, thereby demonstrating the feasibility of the method, but indicating that the efficiency of vaccination by passive inhalation needs further improvement. Altogether our results provide a proof-of-concept that pulmonary vaccination using an SFD-WIV powder vaccine is able to protect chickens from lethal HPAI challenge. If the efficacy of pulmonary vaccination by passive inhalation can be improved, this method might be suitable for mass application. Copyright © 2014 Elsevier Ltd. All rights reserved.

Immunotherapy of Alzheimer's disease (AD): from murine models to anti-amyloid beta (Abeta) human monoclonal antibodies.

PubMed

Geylis, Valeria; Steinitz, Michael

2006-01-01

The deposition of amyloid beta (Abeta) protein is a key pathological feature in Alzheimer's disease (AD). In murine models of AD, both active and passive immunization against Abeta induce a marked reduction in amyloid brain burden and an improvement in cognitive functions. Preliminary results of a prematurely terminated clinical trial where AD patients were actively vaccinated with aggregated Abeta bear resemblance to those documented in murine models. Passive immunization of AD patients with anti-Abeta antibodies, in particular human antibodies, is a strategy that provides a more cautious management and control of any undesired side effects. Sera of all healthy adults contain anti-Abeta IgG autoimmune antibodies. Hence antigen-committed human B-cells are easily immortalized by Epstein-Barr virus (EBV) into anti-Abeta secreting cell lines. Two anti-Abeta human monoclonal antibodies which we recently prepared bind to the N-terminus of Abeta peptide and were shown to stain amyloid plaques in non-fixed brain sections from an AD patient. It is anticipated that specifically selected anti-Abeta human monoclonal antibodies could reduce and inhibit deposits of amyloid in brain while avoiding the cognitive decline that characterizes AD. In the future, this type of antibody may prove to be a promising immune therapy for the disease.

Prenatal passive transfer of maternal immunity in Asian elephants (Elephas maximus).

PubMed

Nofs, Sally A; Atmar, Robert L; Keitel, Wendy A; Hanlon, Cathleen; Stanton, Jeffrey J; Tan, Jie; Flanagan, Joseph P; Howard, Lauren; Ling, Paul D

2013-06-15

Asian (Elephas maximus) and African (Loxodonta africana) elephants exhibit characteristics of endotheliochorial placentation, which is common in carnivore species and is associated with modest maternal to fetal transplacental antibody transfer. However, it remains unknown whether the bulk of passive immune transfer in elephants is achieved prenatally or postnatally through ingestion of colostrum, as has been documented for horses, a species whose medical knowledgebase is often extrapolated for elephants. To address this issue, we took advantage of the fact that many zoo elephants are immunized with tetanus toxoid and/or rabies vaccines as part of their routine health care, allowing a comparison of serum antibody levels against these antigens between dams and neonates. Serum samples were collected from 3 newborn Asian elephant calves at birth (before ingestion of colostrum); 2-4 days after birth; and 2-3 months of age. The findings indicate that the newborns had anti-tetanus toxoid and anti-rabies titers that were equivalent to or higher than the titers of their dams from birth to approximately 3 months of age, suggesting that the majority of maternal-to-fetal transfer is transplacental and higher than expected based on the architecture of the Asian elephant placenta. Copyright © 2013 Elsevier B.V. All rights reserved.

A subcutaneous cellular implant for passive immunization against amyloid-β reduces brain amyloid and tau pathologies.

PubMed

Lathuilière, Aurélien; Laversenne, Vanessa; Astolfo, Alberto; Kopetzki, Erhard; Jacobsen, Helmut; Stampanoni, Marco; Bohrmann, Bernd; Schneider, Bernard L; Aebischer, Patrick

2016-05-01

Passive immunization against misfolded toxic proteins is a promising approach to treat neurodegenerative disorders. For effective immunotherapy against Alzheimer's disease, recent clinical data indicate that monoclonal antibodies directed against the amyloid-β peptide should be administered before the onset of symptoms associated with irreversible brain damage. It is therefore critical to develop technologies for continuous antibody delivery applicable to disease prevention. Here, we addressed this question using a bioactive cellular implant to deliver recombinant anti-amyloid-β antibodies in the subcutaneous tissue. An encapsulating device permeable to macromolecules supports the long-term survival of myogenic cells over more than 10 months in immunocompetent allogeneic recipients. The encapsulated cells are genetically engineered to secrete high levels of anti-amyloid-β antibodies. Peripheral implantation leads to continuous antibody delivery to reach plasma levels that exceed 50 µg/ml. In a proof-of-concept study, we show that the recombinant antibodies produced by this system penetrate the brain and bind amyloid plaques in two mouse models of the Alzheimer's pathology. When encapsulated cells are implanted before the onset of amyloid plaque deposition in TauPS2APP mice, chronic exposure to anti-amyloid-β antibodies dramatically reduces amyloid-β40 and amyloid-β42 levels in the brain, decreases amyloid plaque burden, and most notably, prevents phospho-tau pathology in the hippocampus. These results support the use of encapsulated cell implants for passive immunotherapy against the misfolded proteins, which accumulate in Alzheimer's disease and other neurodegenerative disorders. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A passive cold storage device economic model to evaluate selected immunization location scenarios.

PubMed

Norman, Bryan A; Nourollahi, Sevnaz; Chen, Sheng-I; Brown, Shawn T; Claypool, Erin G; Connor, Diana L; Schmitz, Michelle M; Rajgopal, Jayant; Wateska, Angela R; Lee, Bruce Y

2013-10-25

The challenge of keeping vaccines cold at health posts given the unreliability of power sources in many low- and middle-income countries and the expense and maintenance requirements of solar refrigerators has motivated the development of passive cold storage devices (PCDs), containers that keep vaccines cold without using an active energy source. With different PCDs under development, manufacturers, policymakers and funders need guidance on how varying different PCD characteristics may affect the devices' cost and utility. We developed an economic spreadsheet model representing the lowest two levels of a typical Expanded Program on Immunization (EPI) vaccine supply chain: a district store, the immunization locations that the district store serves, and the transport vehicles that operate between the district store and the immunization locations. The model compares the use of three vaccine storage device options [(1) portable PCDs, (2) stationary PCDs, or (3) solar refrigerators] and allows the user to vary different device (e.g., size and cost) and scenario characteristics (e.g., catchment area population size and vaccine schedule). For a sample set of select scenarios and equipment specification, we found the portable PCD to generally be better suited to populations of 5,000 or less. The stationary PCD replenished once per month can be a robust design especially with a 35L capacity and a cost of $2,500 or less. The solar device was generally a reasonable alternative for most of the scenarios explored if the cost was $2,100 or less (including installation). No one device type dominated over all explored circumstances. Therefore, the best device may vary from country-to-country and location-to-location within a country. This study introduces a quantitative model to help guide PCD development. Although our selected set of explored scenarios and device designs was not exhaustive, future explorations can further alter model input values to represent additional scenarios and device designs. Copyright © 2013 Elsevier Ltd. All rights reserved.

Evaluation of the protective immunogencity of the N, P, M, NV and G proteins of infectious hematopoietic necrosis virus in rainbow trout Oncorhynchus mykiss using DNA vaccines

USGS Publications Warehouse

Corbeil, S.; LaPatra, S.E.; Anderson, E.D.; Jones, J.; Vincent, B.; Hsu, Ya Li; Kurath, G.

1999-01-01

The protective immunogenicity of the nucleoprotein (N), phosphoprotein (P), matrix protein (M), non-virion protein (NV) and glycoprotein (G) of the rhabdovirus infectious hematopoietic necrosis virus (IHNV) was assessed in rainbow trout using DNA vaccine technology. DNA vaccines were produced by amplifying and cloning the viral genes in the plasmid pCDNA 3.1. The protective immunity elicited by each vaccine was evaluated through survival of immunized fry after challenge with live virus. Neutralizing antibody titers were also determined in vaccinated rainbow troutOncorhynchus mykiss fry (mean weight 2 g) and 150 g sockeye salmon Oncorhynchus nerka. The serum from the 150 g fish was also used in passive immunization studies with naïve fry. Our results showed that neither the internal structural proteins (N, P and M) nor the NV protein of IHNV induced protective immunity in fry or neutralizing antibodies in fry and 150 g fish when expressed by a DNA vaccine construct. The G protein, however, did confer significant protection in fry up to 80 d post-immunization and induced protective neutralizing antibodies. We are currently investigating the role of different arms of the fish immune system that contribute to the high level of protection against IHNV seen in vaccinated fish.

Developing injectable immunoglobulins to treat cognitive impairment in Alzheimer's disease.

PubMed

Steinitz, Michael

2008-05-01

Alzheimer's disease is a devastating disorder, clinically characterized by a comprehensive cognitive decline. The novel strategy of anti-amyloid-beta immunotherapy has been suggested following encouraging results obtained in murine models of Alzheimer's disease, in non-human primates, and in small-scale clinical trials. To examine the choice between active or passive anti-amyloid-beta immunization and the choice of the molecule to which the immune machinery should be targeted, which are central issues in future immune therapy of Alzheimer's disease. Research into the new area of Alzheimer's disease immune therapy is primarily based on in vivo and in vitro studies of murine models of Alzheimer's disease. The studies are hence limited to defined genetic deficiencies. In humans, infusion of anti-amyloid-beta antibodies is considered a safer approach than active anti-amyloid-beta vaccination. Alzheimer's-disease-protective anti-amyloid-beta monoclonal antibodies should target specific epitopes within the amyloid beta(1 42) peptide, avoiding possibly harmful binding to the ubiquitous normal amyloid precursor protein. Since Alzheimer's disease immunotherapy requires repeated infusion of antibodies over a prolonged period of time, Alzheimer's disease patients will tolerate such antibodies provided the latter are exclusively of human origin. Human monoclonal antibodies that correspond to ubiquitous anti-amyloid-beta, present in all healthy humans, might bear important protective characteristics.

Oral immunization with rotavirus VP7-CTB fusion expressed in transgenic Arabidopsis thaliana induces antigen-specific IgA and IgG and passive protection in mice

PubMed Central

Li, Yuxian; Guan, Lili; Liu, Xiuming; Liu, Weican; Yang, Jing; Zhang, Xiaomei; Wang, Fawei; Guo, Yongxin; Li, Haiyan; Li, Xiaokun

2018-01-01

Human rotavirus (HRV) is the primary cause of severe gastroenteritis in children. However, there is currently no protective virus for rotavirus available. In the present study, an HRVVP7-cholera toxin B subunit (CTB) fusion protein was expressed in Arabidopsis thaliana. To determine the adjuvant effect of HRVVP7-CTB, HRVVP7 without CTB was expressed in the same manner. HRVVP7-CTB accounted for 0.39% of the total soluble protein (TSP) in the transgenic seeds and 52.65 µg/g of HRVVP7 protein was expressed in these seeds. Mice were immunized with TSP from the transformed seeds and produced serum immunoglobulin G (IgG) and mucosal IgA specifically directed against HRVVP7. Antibody titers were highest in mice orally immunized with the plant-expressed HRVVP7-CTB protein, whereas HRVVP7-CTB-specific IgG neutralized the rotavirus. Suckling pups born from dams immunized with the HRVVP7-CTB fusion protein were protected against challenge with virulent rotavirus. The results of the present study suggest that the HRVVP7-CTB fusion protein produced in A. thaliana may be a rotaviral-specific candidate subunit vaccine. PMID:29805507

Abeta DNA vaccination for Alzheimer's disease: focus on disease prevention.

PubMed

Cribbs, David H

2010-04-01

Pre-clinical and clinical data suggest that the development of a safe and effective anti-amyloid-beta (Abeta) immunotherapy for Alzheimer's disease (AD) will require therapeutic levels of anti-Abeta antibodies, while avoiding proinflammatory adjuvants and autoreactive T cells which may increase the incidence of adverse events in the elderly population targeted to receive immunotherapy. The first active immunization clinical trial with AN1792 in AD patients was halted when a subset of patients developed meningoencephalitis. The first passive immunotherapy trial with bapineuzumab, a humanized monoclonal antibody against the end terminus of Abeta, also encountered some dose dependent adverse events during the Phase II portion of the study, vasogenic edema in 12 cases, which were significantly over represented in ApoE4 carriers. The proposed remedy is to treat future patients with lower doses, particularly in the ApoE4 carriers. Currently there are at least five ongoing anti-Abeta immunotherapy clinical trials. Three of the clinical trials use humanized monoclonal antibodies, which are expensive and require repeated dosing to maintain therapeutic levels of the antibodies in the patient. However in the event of an adverse response to the passive therapy antibody delivery can simply be halted, which may provide a resolution to the problem. Because at this point we cannot readily identify individuals in the preclinical or prodromal stages of AD pathogenesis, passive immunotherapy is reserved for those that already have clinical symptoms. Unfortunately those individuals have by that point accumulated substantial neuropathology in affected regions of the brain. Moreover, if Abeta pathology drives tau pathology as reported in several transgenic animal models, and once established if tau pathology can become self propagating, then early intervention with anti-Abeta immunotherapy may be critical for favorable clinical outcomes. On the other hand, active immunization has several significant advantages, including lower cost and the typical immunization protocol should be much less intrusive to the patient relative to passive therapy, in the advent of Abeta-antibody immune complex-induced adverse events the patients will have to receive immuno-supperssive therapy for an extended period until the anti Abeta antibody levels drop naturally as the effects of the vaccine decays over time. Obviously, improvements in vaccine design are needed to improve both the safety, as well as the efficacy of anti-Abeta immunotherapy. The focus of this review is on the advantages of DNA vaccination for anti-Abeta immunotherapy, and the major hurdles, such as immunosenescence, selection of appropriate molecular adjuvants, universal T cell epitopes, and possibly a polyepitope design based on utilizing existing memory T cells in the general population that were generated in response to childhood or seasonal vaccines, as well as various infections. Ultimately, we believe that the further refinement of our AD DNA epitope vaccines, possibly combined with a prime boost regime will facilitate translation to human clinical trials in either very early AD, or preferably in preclinical stage individuals identified by validated AD biomarkers.

RADIATION EFFECTS ON IMMUNE MECHANISMS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stoner, R.D.; Hale, W.M.

1963-03-01

Experiments were performed on pathogen-free Swiss albino mice to determine the repressive effect of ionizing radiation on immune mechanisms. In animals given sublethal doses of Co/sup 60/ gamma radiation by acute short-term exposure or by chronic long-term exposure at a low dose rate, ability to produce antibody was inhibited or abolished, and natural resistance and active and passive immunity to pneumococcal and Trichinella infections were severely depressed. It appears that the repression resulted from damage to the cellular defensive mechanisms of the host. Active immunity and natural resistance to influenza virus infections were not altered significantly by radiation. Exposure tomore » radiation enhanced the severity of anaphylactic shock markedly in mice previously sensitized to tetanus toxoid and challenged with tetanus toxoid after radiation. Chronic exposure to radiation caused immediate increased sensitivity to fatal anaphylaxis. (auth)« less

Neutralization of Yersinia pestis-mediated macrophage cytotoxicity by anti-LcrV antibodies and its correlation with protective immunity in a mouse model of bubonic plague.

PubMed

Zauberman, Ayelet; Cohen, Sara; Levy, Yinon; Halperin, Gideon; Lazar, Shirley; Velan, Baruch; Shafferman, Avigdor; Flashner, Yehuda; Mamroud, Emanuelle

2008-03-20

Plague is a life-threatening disease caused by Yersinia pestis, for which effective-licensed vaccines and reliable predictors of in vivo immunity are lacking. V antigen (LcrV) is a major Y. pestis virulence factor that mediates translocation of the cytotoxic Yersinia protein effectors (Yops). It is a well-established protective antigen and a part of currently tested plague subunit vaccines. We have developed a highly sensitive in vitro macrophage cytotoxicity neutralization assay which is mediated by anti-LcrV antibodies; and studied the potential use of these neutralizing antibodies as an in vitro correlate of plague immunity in mice. The assay is based on a Y. pestis strain with enhanced cytotoxicity to macrophages in which endogenous yopJ was replaced by the more effectively translocated yopP of Y. enterocolitica O:8. Mice passively immunized with rabbit anti-LcrV IgG or actively immunized with recombinant LcrV were protected against lethal doses of a virulent Y. pestis strain, in a mouse model of bubonic plague. This protection significantly correlated with the in vitro neutralizing activity of the antisera but not with their corresponding ELISA titers. In actively immunized mice, a cutoff value for serum neutralizing activity, above which survival was assured with high degree of confidence, could be established for different vaccination regimes. The impact of overall findings on the potential use of serum neutralizing activity as a correlate of protective immunity is discussed.

Application of rat mast cell incubates as a possible short-time test for sensitizing occupational chemicals.

PubMed

Diel, F; Neidhart, B; Oprée, W

1981-01-01

The direct action of sensitizing occupational chemicals (formaldehyde, phenol, phenylhydrazine, p-aminophenol) on rat mast cells was investigated by determination of histamine using HPLC separation and fluorimetric detection. It turned out that dispensed mast cells from immunized and non-immunized Wistar-rats are more sensitive than small-cut lung tissue slices. Passive cutaneous anaphylaxis was negative after a fortnight sensitizing experiment with the here described occupational chemicals. Short-time tests with rat mast cells reflect anaphylactoid response and are suitable for the screening of sensitizing chemicals.

Myxomatosis: passive immunity in the offspring of immune rabbits (Oryctolagus cuniculus) infested with fleas (Spilopsyllus cuniculi Dale) and exposed to myxoma virus.

PubMed

Sobey, W R; Conolly, D

1975-02-01

Kittens with maternal antibodies to myxoma virus, the offspring of rabbits which had recovered from myxomatosis, were exposed to fleas contaminated with myxoma virus and/or contact with infected rabbits from birth. All kittens died or became infected before 8 weeks of age. When compared with adult animals similarly infected the kittens showed no advantage in terms of survival time or recovery rate attributable to maternal antibodies. Flea transmission of virus was found more effective than contact transmissions.

Myxomatosis: passive immunity in the offspring of immune rabbits (Oryctolagus cuniculus) infested with fleas (Spilopsyllus cuniculi Dale) and exposed to myxoma virus.

PubMed Central

Sobey, W. R.; Conolly, D.

1975-01-01

Kittens with maternal antibodies to myxoma virus, the offspring of rabbits which had recovered from myxomatosis, were exposed to fleas contaminated with myxoma virus and/or contact with infected rabbits from birth. All kittens died or became infected before 8 weeks of age. When compared with adult animals similarly infected the kittens showed no advantage in terms of survival time or recovery rate attributable to maternal antibodies. Flea transmission of virus was found more effective than contact transmissions. PMID:1054058

[Palivizumab: four seasons in Russia].

PubMed

Baranov, A A; Ivanov, D O; Aliamovskaia, G A; Amirova, V R; Antoniuk, I V; Asmolova, G A; Beliaeva, I A; Bokeria, E L; Briukhanova, O A; Vinogradova, I V; Vlasova, E V; Galustian, A N; Gafarova, G V; Gorev, V V; Davydova, I V; Degtiarev, D N; Degtiareva, E A; Dolgikh, V V; Donits, I M; Zakharova, N I; Zernova, L Iu; Zimina, E P; Zuev, V V; Keshishian, E S; Kovalev, I A; Koltunov, I E; Korsunskiĭ, A A; Krivoshchekov, E V; Krsheminskaia, I V; Kuznetsova, S N; Liubimenko, V A; Namazova-Baranova, L S; Nesterenko, É V; Nikolaev, S V; Ovsiannikov, D Iu; Pavlova, T I; Potapova, M V; Rychkova, L V; Safarov, A A; Safina, A I; Skachkova, M A; Soldatova, I G; Turti, T V; Filatova, N A; Shakirova, R M; Ianulevich, O S

2014-01-01

In 2010, the Russian Federation (RF) registered palivizumab--innovative drug, based on monoclonal antibodies for passive immunization of seasonal respiratory syncytial virus (RSV) infection in children of disease severe progress risk group, which include primarily premature infants, children with bronchopulmonary dysplasia and hemodynamically significant congenital heart disease. Currently, palivizumab is included in the list of recommended medicines and medical care standards of different countries, including Russia. In the review the results of Russian research on the progress of RSV infection, its epidemiology and immunization experience gained over the 2010-2014 period are summarized in relation to the foreign data. During the four epidemic seasons palivizumab immunization covered more than 3,200 children of severe RSV infection risk group with a progressive annual increase in the number of patients who received the drug. Geography of palivizumab immunization is also greatly expanded in our country during this time. If during the first two seasons measures of immunization were taken mainly in Moscow and St. Petersburg, at the present time, thirty one territorial entities of the Russian Federation have the experience in the drug application. Analysis of the results of RSV infection immunization (made in several regions) confirms the high clinical efficacy and palivizumab safety already demonstrated in international studies. In addition, the analysis presents the potential to improve the efficiency of the integrated RSV infection immunization programs, realizing in the establishment of high-risk child group register, adequate counseling for parents, as well as the development of the routing of patients and coordination of interaction between different health institutions during the immunization.

[Anti-infective defence strategies and methods of escape from entomologic pathogens under immunologic control of insects].

PubMed

Jarosz, J

1996-01-01

Insect immunity comprises a complex of several distinct systems, both haemocytic and humoral in nature, that cooperate together in a more or less coordinated way to provide protection of the body cavity from invading microorganisms. Insects can respond to infections by a selective synthesis of haemolymph immune proteins that are responsible for antibacterial immunity. Antibacterial activity of insect blood is attributable to innate compounds such as lysozome, and to induced polypeptides or small basic proteins absent in non-immunized insects. The cecropins and attacins in Lepidoptera, and diptericins in Diptera are the inducible antibacterial immune proteins well defined biochemically. Bacterial pathogens and some parasites of insects, preferably entomogenous rhabditid nematodes, have developed the mechanism by which they may counteract insect immunity. This phenomenon is realized either by escaping immune reactions or by degrading antimicrobial factors of haemolymph in an active process. Passive resistance of parasites to insect immunity is a result of a strong evolutionary pressure on parasites to develop mechanisms to escape insect immune reactions or to minimize their effectiveness through changes in the parasite itself. Active resistance to the insect non-self response system involves a partial or total destruction of immune proteins by extracellular proteinases released during parasitism.

Preventive medicines: vaccination, prophylaxis of infectious diseases, disinfectants.

PubMed

Heininger, Ulrich

2011-01-01

Immunizations belong to the most successful interventions in medicine. Like other drugs, vaccines undergo long periods of pre-clinical development, followed by careful clinical testing through study Phases I, II, and III before they receive licensure. A successful candidate vaccine will move on to be an investigational vaccine to undergo three phases of pre-licensure clinical trials in a stepwise fashion before it can be considered for approval, followed by an optional fourth phase of post-marketing assessment. The overall risk-benefit assessment of a candidate vaccine is very critical in making the licensure decision for regulatory authorities, supported by their scientific committees. It includes analyses of immunogenicity, efficacy, reactogenicity or tolerability, and safety of the vaccine. Public trust in vaccines is a key to the success of immunization programs worldwide. Maintaining this trust requires knowledge of the benefits and scientific understanding of real or perceived risks of immunizations. Under certain circumstances, pre- or post-exposure passive immunization can be achieved by administration of immunoglobulines. In terms of prevention of infectious diseases, disinfection can be applied to reduce the risk of transmission of pathogens from patient to patient, health-care workers to patients, patients to health-care workers, and objects or medical devices to patients.

Report of the Committee on Infectious Diseases. Twenty-first Edition, 1988.

ERIC Educational Resources Information Center

American Academy of Pediatrics, Elk Grove Village, IL.

This book is a comprehensive textbook of infectious diseases. It is organized in five parts: (1) active and passive immunization; (2) recommendations for care of children in special circumstances; (3) summaries of infectious diseases; (4) antimicrobial prophylaxis; and (5) antimicrobials. There are six appendices: (1) federal vaccine injury…

Effect of probiotics and prebiotics on food animal immunity

USDA-ARS?s Scientific Manuscript database

The gastrointestinal (GI) tract is the largest interface between an animal’s internal milieu and its exterior environment. As such, it forms a physical barrier between both environments. However, the function of the GI tract in the well-being of an animal is more complex than this passive role. Th...

Host Immune Response to Histophilus somni.

PubMed

Corbeil, Lynette B

2016-01-01

Histophilus somni is known to cause several overlapping syndromes or to be found in genital or upper respiratory carrier states in ruminants. Vaccines have been used for decades, yet efficacy is controversial and mechanisms of protective immunity are not well understood. Since H. somni survives phagocytosis, it has sometimes been considered to be a facultative intercellular parasite, implying that cell-mediated immunity would be critical in protection. However, H. somni not only inhibits phagocyte function, but also is cytotoxic for macrophages. Therefore, it does not live for long periods in healthy phagocytes. Protection of calves against H. somni pneumonia by passive immunization is also evidence that H. somni is more like an extracellular pathogen than an intracellular pathogen. Several studies showed that bovine IgG2 antibodies are more protective than IgG1 antibodies. Even the IgG2 allotypes tend to vary in protection. Of course, antigenic specificity also determines protection. So far, there is most evidence for protection by a 40 K outer membrane protein and by Immunoglobulin binding protein A fibrils. Serology and immunohistochemistry have both been used for immunodiagnosis. Many evasive mechanisms by H. somni have been defined, including decreased phagocyte function, antibodies bound by shed antigens, decreased immune stimulation, and antigenic variation. Interaction of H. somni with other bovine respiratory disease organisms is another layer of pathogenesis. Studies of bovine respiratory syncytial virus (BRSV) and H. somni in calfhood pneumonia revealed an increase in IgE antibodies to H. somni, which were associated with more severe disease of longer duration than with either agent alone. Innate immune mechanisms at the epithelial cell level are also affected by dual infection by BRSV and H. somni as compared to either pathogen alone. Although much more work needs to be done, the complex mechanisms of H. somni immunity are becoming clearer.

The intranasal vaccination of pregnant dams with Intimin and EspB confers protection in neonatal mice from Escherichia coli (EHEC) O157:H7 infection.

PubMed

Rabinovitz, B C; Larzábal, M; Vilte, D A; Cataldi, A; Mercado, E C

2016-05-27

Enterohemorrhagic Escherichia coli (EHEC) O157:H7 is responsible for intestinal disease and hemolytic uremic syndrome (HUS), a serious systemic complication which particularly affects children. In this study, we evaluated whether passive immunization protects from EHEC O157:H7 colonization and renal damage, by using a weaned BALB/c mouse model of infection. Recombinant proteins EspB and the carboxyl-terminal fragment of 280 amino acids of γ-intimin (γ-IntC280) were used in combination with a macrophage-activating lipopeptide-2 (MALP) adjuvant to immunize pregnant mice by the intranasal route. Neonatal mice were allowed to suckle vaccinated or sham-vaccinated dams until weaning when they were challenged by the oral route with a suspension of an E. coli O157:H7 Stx2+ strain. The excretion of the inoculated strain was followed for 72h. All vaccinated dams exhibited elevated serum IgG response against both γ-Int C280 and EspB. Passive immunization of newborn mice resulted in a significant increase in serum IgG titers against γ-Int C280 and a slight increase in EspB-specific antibodies. The neonates from vaccinated dams showed a significant reduction in EHEC O157:H7 colonization 48h post challenge. In addition, the level of plasma urea concentration, a marker of renal failure, was significantly higher in offsprings of sham-vaccinated mice. In conclusion, vaccination of pregnant dams with γ-Int C280 and EspB could reduce colonization and systemic toxicity of EHEC O157:H7 in their suckling offsprings. Copyright © 2016 Elsevier Ltd. All rights reserved.

Approaches to Preventative and Therapeutic HIV vaccines

PubMed Central

Gray, Glenda E.; Laher, Fatima; Lazarus, Erica; Ensoli, Barbara; Corey, Lawrence

2016-01-01

Novel strategies are being researched to discover vaccines to prevent and treat HIV-1. Nonefficacious preventative vaccine approaches include bivalent recombinant gp120 alone, HIV gene insertion into an Adenovirus 5 (Ad5) virus vector and the DNA prime/Ad5 boost vaccine regimen. However, the ALVAC-HIV prime/AIDSVAX® B/E gp120 boost regimen showed 31.2% efficacy at 3.5 years, and is being investigated as clade C constructs with an additional boost. Likewise, although multiple therapeutic vaccines have failed in the past, in a non-placebo controlled trial, a Tat vaccine demonstrated immune cell restoration, reduction of immune activation, and reduced HIV-1 DNA viral load. Monoclonal antibodies for passive immunization or treatment show promise, with VRC01 entering advanced clinical trials. PMID:26985884

COMPUTATION OF ℛ IN AGE-STRUCTURED EPIDEMIOLOGICAL MODELS WITH MATERNAL AND TEMPORARY IMMUNITY.

PubMed

Feng, Zhilan; Han, Qing; Qiu, Zhipeng; Hill, Andrew N; Glasser, John W

2016-03-01

For infectious diseases such as pertussis, susceptibility is determined by immunity, which is chronological age-dependent. We consider an age-structured epidemiological model that accounts for both passively acquired maternal antibodies that decay and active immunity that wanes, permitting reinfection. The model is a 6-dimensional system of partial differential equations (PDE). By assuming constant rates within each age-group, the PDE system can be reduced to an ordinary differential equation (ODE) system with aging from one age-group to the next. We derive formulae for the effective reproduction number ℛ and provide their biological interpretation in some special cases. We show that the disease-free equilibrium is stable when ℛ < 1 and unstable if ℛ > 1.

Human immunization in developing countries: practical and theoretical problems and prospects.

PubMed

Arya, S C

1994-11-01

While measles, pertussis and tetanus were responsible during the early 1990s for nearly two million deaths in developing countries, no deaths were attributable to them in industrialized countries. More than 96% of global deaths by communicable diseases were also from developing countries. Respiratory infections ranked first in communicable morbidity at all ages. Even though vaccines of bacterial or viral origin or a prophylactic for passive immunization are produced in 24, 16 and 15 developing countries, respectively, none of the developing countries manufactures a plasma-derived prophylactic or biological response modifier. Nearly every country relies on import of one or more vaccines. The suboptimal performance of otherwise meritorious products has been due to faulty vaccine administration practices. Expanding populations, poverty and lack of education, cold-chain defects, and inadequate facilities for transport of vaccines to target populations in remote areas have been responsible for the poor performance of vaccines in the community. Mounting foreign debts and budgetary strains resulting from the care and prevention of AIDS/HIV have considerably strained national and international efforts to offer routine vaccinations in childhood and pregnancy. This dismal situation could be tackled through research to obtain environmentally stable products for prophylactic use and monoclonal antibody formulations for passive immunization, and through international financial and technical support. All countries should exercise some technical control of the quality of imported and indigenous vaccines during their use for curative or prophylactic purposes. The involvement of private clinicians in immunizations would strengthen national efforts for control of communicable diseases including AIDS, but this is not enough if the local factors cited above are not improved.

Cellular and Humoral Immunity Protect against Vaginal Zika Virus Infection in Mice.

PubMed

Scott, Jason M; Lebratti, Tania J; Richner, Justin M; Jiang, Xiaoping; Fernandez, Estefania; Zhao, Haiyan; Fremont, Daved H; Diamond, Michael S; Shin, Haina

2018-01-17

Zika virus (ZIKV), which can cause devastating disease in fetuses of infected pregnant women, can be transmitted by mosquito inoculation and sexual routes. Little is known about immune protection against sexually transmitted ZIKV. In this study, we show that previous infection through intravaginal or subcutaneous routes with a contemporary Brazilian strain of ZIKV can protect against subsequent intravaginal challenge with a homologous strain. Both routes of inoculation induced high titers of ZIKV-specific and neutralizing antibody in serum and the vaginal lumen. Virus-specific T cells were recruited to and retained in the female reproductive tract after intravaginal and subcutaneous ZIKV infection. Studies in mice with genetic or acquired deficiencies in B and/or T cells demonstrated that both lymphocyte populations redundantly protect against intravaginal challenge in ZIKV-immune animals. Passive transfer of ZIKV immune IgG or T cells significantly limited intravaginal infection of naïve mice, although antibody more effectively prevented dissemination throughout the reproductive tract. Collectively, our experiments begin to establish the immune correlates of protection against intravaginal ZIKV infection, which should inform vaccination strategies in non-pregnant and pregnant women. IMPORTANCE The recent ZIKV epidemic resulted in devastating outcomes in fetuses and may affect reproductive health. Unlike other flaviviruses, ZIKV can be spread by sexual contact as well as a mosquito vector. While previous studies have identified correlates of protection for mosquito-mediated infection, few have focused on immunity against sexual transmission. As exposure to ZIKV via mosquito bite has likely occurred to many living in endemic areas, our study addresses whether this route of infection can protect against subsequent sexual exposure. We demonstrate that subcutaneous ZIKV infection can protect against subsequent vaginal infection by generating both local antiviral T cell and antibody responses. Our research begins to define the immune correlates of protection for ZIKV infection in the vagina and provides a foundation for testing ZIKV vaccines against sexual transmission. Copyright © 2018 American Society for Microbiology.

The host immune response to Clostridium difficile infection

PubMed Central

2013-01-01

Clostridium difficile infection (CDI) is the most common infectious cause of healthcare-acquired diarrhoea. Outcomes of C. difficile colonization are varied, from asymptomatic carriage to fulminant colitis and death, due in part to the interplay between the pathogenic virulence factors of the bacterium and the counteractive immune responses of the host. Secreted toxins A and B are the major virulence factors of C. difficile and induce a profound inflammatory response by intoxicating intestinal epithelial cells causing proinflammatory cytokine release. Host cell necrosis, vascular permeability and neutrophil infiltration lead to an elevated white cell count, profuse diarrhoea and in severe cases, dehydration, hypoalbuminaemia and toxic megacolon. Other bacterial virulence factors, including surface layer proteins and flagella proteins, are detected by host cell surface signal molecules that trigger downstream cell-mediated immune pathways. Human studies have identified a role for serum and faecal immunoglobulin levels in protection from disease, but the recent development of a mouse model of CDI has enabled studies into the precise molecular interactions that trigger the immune response during infection. Key effector molecules have been identified that can drive towards a protective anti-inflammatory response or a damaging proinflammatory response. The limitations of current antimicrobial therapies for CDI have led to the development of both active and passive immunotherapies, none of which have, as yet been formally approved for CDI. However, recent advances in our understanding of the molecular basis of host immune protection against CDI may provide an exciting opportunity for novel therapeutic developments in the future. PMID:25165542

A recombinant bivalent fusion protein rVE confers active and passive protection against Yersinia enterocolitica infection in mice.

PubMed

Singh, Amit Kumar; Kingston, Joseph Jeyabalaji; Murali, Harishchandra Sripathy; Batra, Harsh Vardhan

2014-03-05

In the present study, a bivalent chimeric protein rVE comprising immunologically active domains of Yersinia pestis LcrV and YopE was assessed for its prophylactic abilities against Yersinia enterocolitica O:8 infection in murine model. Mice immunized with rVE elicited significantly higher antibody titers with substantial contribution from the rV component (3:1 ratio). Robust and significant resistance to Y. enterocolitica infection with 100% survival (P<0.001) was seen in rVE vaccinated mice when intra peritoneal (I.P.) challenged with 10(8)CFU of Y. enterocolitica O:8 against the 75%, 60% and 75% survival seen in mice immunized with rV, rE, rV+rE, respectively. Macrophage monolayer supplemented with anti-rVE polysera illustrated efficient protection (89.41% survival) against challenge of Y. enterocolitica O:8. In contrast to sera from sham-immunized mice, immunization with anti-rVE polysera provided complete protection to BALB/c mice against I.P. challenge with 10(8)CFU of Y. enterocolitica O:8 and developed no conspicuous signs of infection in necropsy. The histopathological analysis of microtome sections confirmed significantly reduced lesion size or no lesion in liver and intestine upon infection in anti-rVE immunized mice. The findings from this study demonstrated the fusion protein rVE as a potential candidate subunit vaccine and showed the functional role of antibodies in protection against Y. enterocolitica infections. Copyright © 2014 Elsevier Ltd. All rights reserved.

Immunotherapy for the treatment of drug abuse.

PubMed

Kosten, Thomas; Owens, S Michael

2005-10-01

Antibody therapy (as either active or passive immunization) is designed primarily to prevent drugs of abuse from entering the central nervous system (CNS). Antidrug antibodies reduce rush, euphoria, and drug distribution to the brain at doses that exceed the apparent binding capacity of the antibody. This is accomplished through a pharmacokinetic antagonism, which reduces the amount of drug in the brain, the rate of clearance across the blood-brain barrier, and the volume of drug distribution. Because the antibodies remain primarily in the circulatory system, they have no apparent central nervous system side effects. Active immunization with drug-protein conjugate vaccines has been tested for cocaine, heroin, methamphetamine, and nicotine in animal, with 1 cocaine and 3 nicotine vaccines in Phase 2 human trials. Passive immunization with high affinity monoclonal antibodies has been tested for cocaine, methamphetamine, nicotine, and phencyclidine (PCP) in preclinical animal models. Antibodies have 2 immediate clinical applications in drug abuse treatment: to treat drug overdose and to reduce relapse to drug use in addicted patients. The specificity of the therapies, the lack of addiction liability, minimal side effects, and long-lasting protection against drug use offer major therapeutic benefit over conventional small molecule agonists and antagonists. Immunotherapies can also be combined with other antiaddiction medications and enhance behavioral therapies. Current immunotherapies already show efficacy, but improved antigen design and antibody engineering promise highly specific and rapidly developed treatments for both existing and future addictions.

Nasopharyngeal infection by Streptococcus pyogenes requires superantigen-responsive Vβ-specific T cells

PubMed Central

Zeppa, Joseph J.; Kasper, Katherine J.; Mohorovic, Ivor; Mazzuca, Delfina M.

2017-01-01

The globally prominent pathogen Streptococcus pyogenes secretes potent immunomodulatory proteins known as superantigens (SAgs), which engage lateral surfaces of major histocompatibility class II molecules and T-cell receptor (TCR) β-chain variable domains (Vβs). These interactions result in the activation of numerous Vβ-specific T cells, which is the defining activity of a SAg. Although streptococcal SAgs are known virulence factors in scarlet fever and toxic shock syndrome, mechanisms by how SAgs contribute to the life cycle of S. pyogenes remain poorly understood. Herein, we demonstrate that passive immunization against the Vβ8-targeting SAg streptococcal pyrogenic exotoxin A (SpeA), or active immunization with either wild-type or a nonfunctional SpeA mutant, protects mice from nasopharyngeal infection; however, only passive immunization, or vaccination with inactive SpeA, resulted in high-titer SpeA-specific antibodies in vivo. Mice vaccinated with wild-type SpeA rendered Vβ8+ T cells poorly responsive, which prevented infection. This phenotype was reproduced with staphylococcal enterotoxin B, a heterologous SAg that also targets Vβ8+ T cells, and rendered mice resistant to infection. Furthermore, antibody-mediated depletion of T cells prevented nasopharyngeal infection by S. pyogenes, but not by Streptococcus pneumoniae, a bacterium that does not produce SAgs. Remarkably, these observations suggest that S. pyogenes uses SAgs to manipulate Vβ-specific T cells to establish nasopharyngeal infection. PMID:28794279

Reproducing SIVΔnef vaccine correlates of protection: trimeric gp41 antibody concentrated at mucosal front lines

PubMed Central

Voss, James E.; Macauley, Matthew S.; Rogers, Kenneth A.; Villinger, Francois; Duan, Lijie; Shang, Liang; Fink, Elizabeth A.; Andrabi, Raiees; Colantonio, Arnaud D.; Robinson, James E.; Johnson, R. Paul; Burton, Dennis R.; Haase, Ashley T.

2016-01-01

Vaccination with SIVmac239Δnef provides robust protection against subsequent challenge with wild type SIV, but safety issues have precluded designing an HIV-1 vaccine based on a live attenuated virus concept. Safe immunogens and adjuvants that could reproduce identified immune correlates of SIVmac239Δnef protection therefore offer an alternative path for development of an HIV vaccine. Here we describe SIV envelope trimeric gp41 (gp41t) immunogens based on a protective correlate of antibodies to gp41t concentrated on the path of virus entry by the neonatal Fc receptor (FcRn) in cervical vaginal epithelium. We developed a gp41t immunogen-MPLA adjuvant liposomal nanoparticle for intra-muscular immunization and a gp41t-Fc immunogen for intranasal immunization for pilot studies in mice, rabbits, and rhesus macaques. Repeated immunizations to mimic persistent antigen exposure in infection elicited gp41t antibodies in rhesus macaques that were detectable in FcRn+ cervical vaginal epithelium, thus recapitulating one key feature of SIVmac239Δnef vaccinated and protected animals. While this strategy did not reproduce the system of local production of antibody in SIVmac239Δnef-vaccinated animals, passive immunization experiments supported the concept that sufficiently high levels of antibody can be concentrated by the FcRn at mucosal frontlines, thus setting the stage for assessing protection against vaginal challenge by gp41t immunization. PMID:27428745

Level of Interactivity of Videodisc Instruction on College Students' Recall of AIDS Information.

ERIC Educational Resources Information Center

Kritch, Kale M.; And Others

1995-01-01

Two experiments confirmed the greater effectiveness of constructed-response interactive videodisc instruction when compared to a click-to-continue or passive viewing formats on posttest recall of Acquired Immune Deficiency Syndrome (AIDS) information by 101 college students. The necessity of constructing answers appears to be an important factor…

Identifying genetic loci controlling neonatal passive transfer of immunity using a hybrid genotyping strategy

USDA-ARS?s Scientific Manuscript database

Colostrum intake is critical to a piglet’s survival and can be measured by precipitating out the gamma-immunoglobulins from serum with ammonium sulfate (immunocrit). Genetic analysis of immunocrits on 5,312 piglets indicated that the heritabilities (se) for direct and maternal effects were 0.13(0.06...

Lactogenic immunity and vaccines for porcine epidemic diarrhea virus (PEDV): historical and current concepts

USDA-ARS?s Scientific Manuscript database

Morbidity, mortality, and loss of productivity from enteric diseases in neonatal piglets cost swine producers millions of dollars annually. In 2013-2014, the porcine epidemic diarrhea virus (PEDV) outbreak led to $900 million to $1.8 billion in annual losses to US swine producers. Passive lactogeni...

Status of vaccines for porcine epidemic diarrhea virus in the United States and Canada

USDA-ARS?s Scientific Manuscript database

In 2013, porcine epidemic diarrhea virus (PEDV) emerged in the United States as a rapidly spreading epidemic causing dramatic death losses in suckling piglets. Neonatal piglets are most vulnerable to clinical disease and their only protection is passive immunity from their dam. At the end of the thi...

The effects of pre- and probiotics on the host immune response

USDA-ARS?s Scientific Manuscript database

The gastrointestinal (GI) tract is the largest interface between an animal’s internal milieu and its exterior environment. As such, it forms a physical barrier between both environments. However, the function of the GI tract in the well-being of an animal is more complex than this passive role. T...

Survival of priceless cells: active and passive protection of embryonic stem cells against immune destruction.

PubMed

Utermöhlen, Olaf; Krönke, Martin

2007-06-15

This review focuses on our current knowledge of the mechanisms employed by embryonic stem (ES) cells to avoid destruction by cell-mediated immune responses. Recently, ES cells have been found to shield themselves against cytotoxic effector cells by expressing CD95L and serine protease inhibitor SPI-6 mediating apoptosis of the cytotoxic cells and inactivation of granzyme B, respectively. These findings are discussed in view of their implications for using ES cell-derived transplants in regenerative medicine as well as for our understanding of early embryonic stages during invasion and implantation.

Neutralizing activity and protective immunity to ricin toxin conferred by B subunit (RTB)-specific Fab fragments.

PubMed

Yermakova, Anastasiya; Mantis, Nicholas J

2013-09-01

SylH3 and 24B11 are murine monoclonal antibodies directed against different epitopes on ricin toxin's binding (RTB) subunit that have been shown to passively protect mice against ricin challenge. Here we report that Fab fragments of SylH3 and 24B11 neutralize ricin in a cell based assay, and in a mouse challenge model as effectively as their respective full length parental IgGs. These data demonstrate that immunity to ricin can occur independent of Fc-mediated clearance. Copyright © 2013 Elsevier Ltd. All rights reserved.

AAVrh.10-mediated expression of an anti-cocaine antibody mediates persistent passive immunization that suppresses cocaine-induced behavior.

PubMed

Rosenberg, Jonathan B; Hicks, Martin J; De, Bishnu P; Pagovich, Odelya; Frenk, Esther; Janda, Kim D; Wee, Sunmee; Koob, George F; Hackett, Neil R; Kaminsky, Stephen M; Worgall, Stefan; Tignor, Nicole; Mezey, Jason G; Crystal, Ronald G

2012-05-01

Cocaine addiction is a major problem affecting all societal and economic classes for which there is no effective therapy. We hypothesized an effective anti-cocaine vaccine could be developed by using an adeno-associated virus (AAV) gene transfer vector as the delivery vehicle to persistently express an anti-cocaine monoclonal antibody in vivo, which would sequester cocaine in the blood, preventing access to cognate receptors in the brain. To accomplish this, we constructed AAVrh.10antiCoc.Mab, an AAVrh.10 gene transfer vector expressing the heavy and light chains of the high affinity anti-cocaine monoclonal antibody GNC92H2. Intravenous administration of AAVrh.10antiCoc.Mab to mice mediated high, persistent serum levels of high-affinity, cocaine-specific antibodies that sequestered intravenously administered cocaine in the blood. With repeated intravenous cocaine challenge, naive mice exhibited hyperactivity, while the AAVrh.10antiCoc.Mab-vaccinated mice were completely resistant to the cocaine. These observations demonstrate a novel strategy for cocaine addiction by requiring only a single administration of an AAV vector mediating persistent, systemic anti-cocaine passive immunity.

Protection of mice from fatal bubonic and pneumonic plague by passive immunization with monoclonal antibodies against the F1 protein of Yersinia pestis.

PubMed

Anderson, G W; Worsham, P L; Bolt, C R; Andrews, G P; Welkos, S L; Friedlander, A M; Burans, J P

1997-04-01

Monoclonal antibodies (MAbs) to the fraction 1 (F1) protein of Yersinia pestis protected mice against fatal pneumonic as well as bubonic plague from wild-type F1+ organisms. The rare isolation of a virulent F1- isolate from surviving animals supports earlier studies suggesting that improved vaccines should consist of immunogens to protect against F1- variants. The high degree of protection with IgG MAb suggests that secretory IgA is not required for protection from pneumonic plague.

Pneumonic plague pathogenesis and immunity in Brown Norway rats.

PubMed

Anderson, Deborah M; Ciletti, Nancy A; Lee-Lewis, Hanni; Elli, Derek; Segal, Joshua; DeBord, Kristin L; Overheim, Katie A; Tretiakova, Maria; Brubaker, Robert R; Schneewind, Olaf

2009-03-01

The Brown Norway rat was recently described as a bubonic plague model that closely mimics human disease. We therefore evaluated the Brown Norway rat as an alternative small animal model for pneumonic plague and characterized both the efficacy and potency of vaccine candidates. When infected by intranasal instillation, these rats rapidly developed fatal pneumonic plague within 2 to 4 days of infection. Plague disease was characterized by severe alveolar edema and vascular hemorrhage in the lung in addition to fulminant necrotizing pneumonia caused by massive bacterial replication and inflammation. Twenty-four hours before death, animals developed systemic disease with an apparent delayed inflammatory response. We evaluated the ability of the protective antigen, LcrV, and a mutant derivative, V10, to protect these rats from pneumonic plague. Both were highly effective vaccines because complete protection was observed at challenge doses of 7500 LD(50). Antibody analyses suggested stronger potency of V10 immune sera compared with LcrV in the passive transfer of immunity to bubonic plague, with multiple neutralizing epitopes in LcrV. Taken together, these data demonstrate the effectiveness of inhibiting type III secretion in the prevention of pneumonic plague in rats and reveal critical contributions from both the cellular and humoral immune systems. Thus, the Brown Norway rat is an appealing alternative small animal model for the study of pneumonic plague pathogenesis and immunity.

Immunity Elicited by an Experimental Vaccine Based on Recombinant Flagellin-Porcine Circovirus Type 2 Cap Fusion Protein in Piglets

PubMed Central

Wang, Jing; Wei, Li; Quan, Rong; Yang, Jiayu; Yan, Xu; Li, Zixuan; She, Ruiping; Hu, Fengjiao; Liu, Jue

2016-01-01

In a recent study, we reported that a recombinant protein from fusion expression of flagellin to porcine circovirus type 2 (PCV2) Cap induced robust humoral and cell-mediated immunity that afforded full protection for PCV2 infection using BALB/c mice. Here, we further evaluated the immunogenicity and protection of the recombinant protein using specific pathogen free (SPF) pigs. Twenty-five 3-week-old piglets without passively acquired immunity were divided into 5 groups. All piglets except negative controls were challenged with a virulent PCV2 at 21 days after booster vaccination and necropsied at 21 days post-challenge. Vaccination of piglets with the recombinant protein without adjuvant induced strong humoral and cellular immune responses as observed by high levels of PCV2-specific IgG antibodies and neutralizing antibodies, as well as frequencies of PCV2-specific IFN-γ-secreting cells that conferred good protection against PCV2 challenge, with significant reduced PCV2 viremia, mild lesions, low PCV2 antigen-positive cells, as well as improved body weight gain, comparable to piglets vaccinated with a commercial PCV2 subunit vaccine. These results further demonstrated that the recombinant flagellin-Cap fusion protein is capable of inducing solid protective humoral and cellular immunity when administered to pigs, thereby becoming an effective PCV2 vaccine candidate for control of PCV2 infection. PMID:26848967

Humoral Immunity Provides Resident Intestinal Eosinophils Access to Luminal Antigen via Eosinophil-Expressed Low-Affinity Fcγ Receptors.

PubMed

Smith, Kalmia M; Rahman, Raiann S; Spencer, Lisa A

2016-11-01

Eosinophils are native to the healthy gastrointestinal tract and are associated with inflammatory diseases likely triggered by exposure to food allergens (e.g., food allergies and eosinophilic gastrointestinal disorders). In models of allergic respiratory diseases and in vitro studies, direct Ag engagement elicits eosinophil effector functions, including degranulation and Ag presentation. However, it was not known whether intestinal tissue eosinophils that are separated from luminal food Ags by a columnar epithelium might similarly engage food Ags. Using an intestinal ligated loop model in mice, in this study we determined that resident intestinal eosinophils acquire Ag from the lumen of Ag-sensitized but not naive mice in vivo. Ag acquisition was Ig-dependent; intestinal eosinophils were unable to acquire Ag in sensitized Ig-deficient mice, and passive immunization with immune serum or Ag-specific IgG was sufficient to enable intestinal eosinophils in otherwise naive mice to acquire Ag in vivo. Intestinal eosinophils expressed low-affinity IgG receptors, and the activating receptor FcγRIII was necessary for Ig-mediated acquisition of Ags by isolated intestinal eosinophils in vitro. Our combined data suggest that intestinal eosinophils acquire lumen-derived food Ags in sensitized mice via FcγRIII Ag focusing and that they may therefore participate in Ag-driven secondary immune responses to oral Ags. Copyright © 2016 by The American Association of Immunologists, Inc.

The role of T and B cells in human atherosclerosis and atherothrombosis

PubMed Central

Ammirati, E; Moroni, F; Magnoni, M; Camici, P G

2015-01-01

Far from being merely a passive cholesterol accumulation within the arterial wall, the development of atherosclerosis is currently known to imply both inflammation and immune effector mechanisms. Adaptive immunity has been implicated in the process of disease initiation and progression interwined with traditional cardiovascular risk factors. Although the body of knowledge regarding the correlation between atherosclerosis and immunity in humans is growing rapidly, a relevant proportion of it derives from studies carried out in animal models of cardiovascular disease (CVD). However, while the mouse is a well-suited model, the results obtained therein are not fully transferrable to the human setting due to intrinsic genomic and environmental differences. In the present review, we will discuss mainly human findings, obtained either by examination of post-mortem and surgical atherosclerotic material or through the analysis of the immunological profile of peripheral blood cells. In particular, we will discuss the findings supporting a pro-atherogenic role of T cell subsets, such as effector memory T cells or the potential protective function of regulatory T cells. Recent studies suggest that traditional T cell-driven B2 cell responses appear to be atherogenic, while innate B1 cells appear to exert a protective action through the secretion of naturally occurring antibodies. The insights into the immune pathogenesis of atherosclerosis can provide new targets in the quest for novel therapeutic targets to abate CVD morbidity and mortality. PMID:25352024

Classification of current anticancer immunotherapies

PubMed Central

Vacchelli, Erika; Pedro, José-Manuel Bravo-San; Buqué, Aitziber; Senovilla, Laura; Baracco, Elisa Elena; Bloy, Norma; Castoldi, Francesca; Abastado, Jean-Pierre; Agostinis, Patrizia; Apte, Ron N.; Aranda, Fernando; Ayyoub, Maha; Beckhove, Philipp; Blay, Jean-Yves; Bracci, Laura; Caignard, Anne; Castelli, Chiara; Cavallo, Federica; Celis, Estaban; Cerundolo, Vincenzo; Clayton, Aled; Colombo, Mario P.; Coussens, Lisa; Dhodapkar, Madhav V.; Eggermont, Alexander M.; Fearon, Douglas T.; Fridman, Wolf H.; Fučíková, Jitka; Gabrilovich, Dmitry I.; Galon, Jérôme; Garg, Abhishek; Ghiringhelli, François; Giaccone, Giuseppe; Gilboa, Eli; Gnjatic, Sacha; Hoos, Axel; Hosmalin, Anne; Jäger, Dirk; Kalinski, Pawel; Kärre, Klas; Kepp, Oliver; Kiessling, Rolf; Kirkwood, John M.; Klein, Eva; Knuth, Alexander; Lewis, Claire E.; Liblau, Roland; Lotze, Michael T.; Lugli, Enrico; Mach, Jean-Pierre; Mattei, Fabrizio; Mavilio, Domenico; Melero, Ignacio; Melief, Cornelis J.; Mittendorf, Elizabeth A.; Moretta, Lorenzo; Odunsi, Adekunke; Okada, Hideho; Palucka, Anna Karolina; Peter, Marcus E.; Pienta, Kenneth J.; Porgador, Angel; Prendergast, George C.; Rabinovich, Gabriel A.; Restifo, Nicholas P.; Rizvi, Naiyer; Sautès-Fridman, Catherine; Schreiber, Hans; Seliger, Barbara; Shiku, Hiroshi; Silva-Santos, Bruno; Smyth, Mark J.; Speiser, Daniel E.; Spisek, Radek; Srivastava, Pramod K.; Talmadge, James E.; Tartour, Eric; Van Der Burg, Sjoerd H.; Van Den Eynde, Benoît J.; Vile, Richard; Wagner, Hermann; Weber, Jeffrey S.; Whiteside, Theresa L.; Wolchok, Jedd D.; Zitvogel, Laurence; Zou, Weiping

2014-01-01

During the past decades, anticancer immunotherapy has evolved from a promising therapeutic option to a robust clinical reality. Many immunotherapeutic regimens are now approved by the US Food and Drug Administration and the European Medicines Agency for use in cancer patients, and many others are being investigated as standalone therapeutic interventions or combined with conventional treatments in clinical studies. Immunotherapies may be subdivided into “passive” and “active” based on their ability to engage the host immune system against cancer. Since the anticancer activity of most passive immunotherapeutics (including tumor-targeting monoclonal antibodies) also relies on the host immune system, this classification does not properly reflect the complexity of the drug-host-tumor interaction. Alternatively, anticancer immunotherapeutics can be classified according to their antigen specificity. While some immunotherapies specifically target one (or a few) defined tumor-associated antigen(s), others operate in a relatively non-specific manner and boost natural or therapy-elicited anticancer immune responses of unknown and often broad specificity. Here, we propose a critical, integrated classification of anticancer immunotherapies and discuss the clinical relevance of these approaches. PMID:25537519

Potential immediate hypersensitivity reactions following immunization in preschool aged children in Victoria, Australia.

PubMed

Baxter, C-M; Clothier, H J; Perrett, K P

2018-04-06

Immediate hypersensitivity reactions (IHR) are rare but potentially serious adverse events following immunization (AEFI). Surveillance of Adverse Events following Vaccination in the Community (SAEFVIC) is an enhanced passive surveillance system that collects, analyses and reports information about AEFI in Victoria, Australia. We describe the incidence, timing and type of potential IHR following vaccination in preschool children reported over an 8-year period. A total of 2110 AEFI were reported in 1620 children, of which 23.5% (496) were classified as potential IHR. Of these, 37.1% (184) were suspected to be IgE-mediated, (including anaphylaxis, angioedema and/or urticaria) and 83.5% (414) occurred within 15 minutes of vaccination. The incidence of potential IHR was 5.4 per 100,000 doses, with that of suspected IgE-mediated IHR being 2.0 per 100,000 doses. The incidence of anaphylaxis was extremely low (0.13 per 100,000 doses) and is consistent with other published studies. Potential IHR following immunization should be reported to appropriate local pharmacovigilance systems and patients reviewed by specialists able to evaluate, investigate and manage future vaccinations.

Active targeted delivery of immune therapeutics to lymph nodes.

PubMed

Bahmani, Baharak; Vohra, Ishaan; Kamaly, Nazila; Abdi, Reza

2018-02-01

Organ transplantation is a life-saving procedure and the only option for patients with end-organ failure. Immune therapeutics have been key to the success of organ transplantation. However, immune therapeutics are still unable to eliminate graft rejection and their toxicity has been implicated in poorer long-term transplant outcomes. Targeted nanodelivery has the potential to enhance not only the therapeutic index but also the bioavailability of the immune therapeutics. One of the key sites of immune therapeutics delivery is lymph node where the priming of immune cells occur. The focus of this review is on nanomedicine research to develop the targeted delivery of immune therapeutics to lymph nodes for controlling immune activation. As nanomedicine creates its niche in clinical care, it provides novel immunotherapy platforms for transplant recipients. Draining lymph nodes are the primary loci of immune activation and represent a formidable site for delivery of wide variety of immune therapeutics. There have been relentless efforts to improve the properties of nanomedicines, to have in-depth knowledge of antigen and drug loading, and, finally, to explore various routes of passive and active targeted delivery to lymph nodes. The application of nanotechnology principles in the delivery of immune therapeutics to the lymph node has created enormous excitement as a paradigm shifting approach that enables targeted delivery of a gamut of molecules to achieve a desired immune response. Therefore, innovative strategies that improve their efficacy while reducing their toxicity are among the highest unmet needs in transplantation.

Promotion of ulcerative duodenitis in young ferrets by oral immunization with Helicobacter mustelae and muramyl dipeptide.

PubMed

Whary, M T; Palley, L S; Batchelder, M; Murphy, J C; Yan, L; Taylor, N S; Fox, J G

1997-06-01

The purpose of this study was to determine whether oral immunization of ferret kits with a whole-cell sonicate of Helicobacter mustelae lysate (Hml) and the adjuvant muramyl dipeptide (MDP) would reduce the incidence of natural colonization with H. mustelae and the extent of Helicobacter-associated gastritis by enhancing the host mucosal immune response. Between the ages of 4 and 11 weeks, 44 ferret kits were gavaged with Hml and various doses of MDP. The extent of gastritis and duodenitis and the immune response to H. mustelae were evaluated. All kits became colonized naturally with H. mustelae and the majority developed mild to severe gastritis and duodenitis. Kits that received Hml with MDP developed significantly greater inflammation of the gastric antrum and duodenum, as compared to kits vaccinated with Hml alone. Vaccination with Hml and 50 micrograms of MDP was associated with severe lesions in the proximal duodenum characterized by accumulation of mononuclear inflammatory cells, mucosal erosion, and ulceration. Although serum antibody specific for H. mustelae in 4-week-old kits was approximately 50% of adult levels, a finding attributable to passively acquired maternal antibody, both systemic and mucosal antibody levels became depressed over time despite oral vaccination. The humoral immune response was sufficiently low to prevent detection of any significant dose effect of MDP on antibody levels among experimental groups. Oral vaccination of young ferrets with Hml and 50 micrograms MDP increased the risk of Helicobacter-associated mucosal ulceration in the proximal duodenum, which was associated with low humoral (but significant cell-mediated) immune responses to H. mustelae. In retrospect, the frequency of vaccination may have suppressed the systemic humoral immune response, thereby promoting mucosal damage by H. mustelae. The 50-microgram dose of MDP enhanced the cell-mediated immune response, which indirectly contributed to development of severe lesions. The increased frequency of mucosal damage associated with this vaccination regimen enhances the value of the ferret model for studying duodenal ulceration secondary to Helicobacter infection.

Differential effects of immunotherapy with antibodies targeting α-synuclein oligomers and fibrils in a transgenic model of synucleinopathy.

PubMed

El-Agnaf, Omar; Overk, Cassia; Rockenstein, Edward; Mante, Michael; Florio, Jazmin; Adame, Anthony; Vaikath, Nishant; Majbour, Nour; Lee, Seung-Jae; Kim, Changyoun; Masliah, Eliezer; Rissman, Robert A

2017-08-01

Disorders with progressive accumulation of α-synuclein (α-syn) are a common cause of dementia and parkinsonism in the aging population. Accumulation and propagation of α-syn play a role in the pathogenesis of these disorders. Previous studies have shown that immunization with antibodies that recognize C-terminus of α-syn reduces the intra-neuronal accumulation of α-syn and related deficits in transgenic models of synucleinopathy. These studies employed antibodies that recognize epitopes within monomeric and aggregated α-syn that were generated through active immunization or administered via passive immunization. However, it is possible that more specific effects might be achieved with antibodies recognizing selective species of the α-syn aggregates. In this respect we recently developed antibodies that differentially recognized various oligomers (Syn-O1, -O2, and -O4) and fibrilar (Syn-F1 and -F2) forms of α-syn. For this purpose wild-type α-syn transgenic (line 61) mice were immunized with these 5 different antibodies and neuropathologically and biochemically analyzed to determine which was most effective at reducing α-syn accumulation and related deficits. We found that Syn-O1, -O4 and -F1 antibodies were most effective at reducing accumulation of α-syn oligomers in multiple brain regions and at preventing neurodegeneration. Together this study supports the notion that selective antibodies against α-syn might be suitable for development new treatments for synucleinopathies such as PD and DLB. Published by Elsevier Inc.

Differential effects of immunotherapy with antibodies targeting α-synuclein oligomers and fibrils in a transgenic model of synucleinopathy

PubMed Central

El-Agnaf, Omar; Overk, Cassia; Rockenstein, Edward; Mante, Michael; Florio, Jazmin; Adame, Anthony; Vaikath, Nishant; Majbour, Nour; Lee, Seung-Jae; Kim, Changyoun; Masliah, Eliezer; Rissman, Robert A.

2018-01-01

Disorders with progressive accumulation of α-synuclein (α-syn) are a common cause of dementia and parkinsonism in the aging population. Accumulation and propagation of α-syn play a role in the pathogenesis of these disorders. Previous studies have shown that immunization with antibodies that recognize C-terminus of α-syn reduces the intra-neuronal accumulation of α-syn and related deficits in transgenic models of synucleinopathy. These studies employed antibodies that recognize epitopes within monomeric and aggregated α-syn that were generated through active immunization or administered via passive immunization. However, it is possible that more specific effects might be achieved with antibodies recognizing selective species of the α-syn aggregates. In this respect we recently developed antibodies that differentially recognized various oligomers (Syn-O1, -O2, and -O4) and fibrilar (Syn-F1 and -F2) forms of α-syn. For this purpose wild-type α-syn transgenic (line 61) mice were immunized with these 5 different antibodies and neuropathologically and biochemically analyzed to determine which was most effective at reducing α-syn accumulation and related deficits. We found that Syn-O1, -O4 and -F1 antibodies were most effective at reducing accumulation of α-syn oligomers in multiple brain regions and at preventing neurodegeneration. Together this study supports the notion that selective antibodies against α-syn might be suitable for development new treatments for synucleinopathies such as PD and DLB. PMID:28476636

Pan-Canadian assessment of pandemic immunization data collection: study methodology

PubMed Central

2010-01-01

Background The collection of individual-level pandemic (H1N1) 2009 influenza immunization data was considered important to facilitate optimal vaccine delivery and accurate assessment of vaccine coverage. These data are also critical for research aimed at evaluating the new vaccine's safety and effectiveness. Systems used to collect immunization data include manual approaches in which data are collected and retained on paper, electronic systems in which data are captured on computer at the point of vaccination and hybrid systems which are comprised of both computerized and manual data collection components. This study's objective was to compare the efficiencies and perceptions of data collection methods employed during Canada's pandemic (H1N1) 2009 influenza vaccination campaign. Methods/Design A pan-Canadian observational study was conducted in a convenience sample of public health clinics and healthcare institutions during the H1N1 vaccination campaign in the fall of 2009. The study design consisted of three stages: Stage 1 involved passive observation of the site's layout, processes and client flow; Stage 2 entailed timing site staff on 20 clients through five core immunization tasks: i) client registration, ii) medical history collection, iii) medical history review, iv) vaccine administration record keeping and v) preparation of proof of vaccine administration for the client; in Stage 3, site staff completed a questionnaire regarding perceived usability of the site's data collection approach. Before the national study began, a pilot study was conducted in three seasonal influenza vaccination sites in Ontario, to both test that the proposed methodology was logistically feasible and to determine inter-rater reliability in the measurements of the research staff. Comparative analyses will be conducted across the range of data collection methods with respect to time required to collect immunization data, number and type of individual-level data elements collected, and clinic staff perceptions of the usability of the method employed at their site, using analysis of variance (ANOVA). Discussion Various data collection methods were employed at immunization sites across Canada during the pandemic (H1N1) 2009 influenza vaccination campaign. Our comparison of methods can facilitate planning an efficient, coordinated approach for collecting immunization data in future influenza seasons. PMID:20624270

Pan-Canadian assessment of pandemic immunization data collection: study methodology.

PubMed

Pereira, Jennifer A; Quach, Susan; Heidebrecht, Christine; Foisy, Julie; Quan, Sherman; Finkelstein, Michael; Sikora, Christopher A; Bettinger, Julie A; Buckeridge, David L; McCarthy, Anne; Deeks, Shelley; Kwong, Jeffrey C

2010-06-08

The collection of individual-level pandemic (H1N1) 2009 influenza immunization data was considered important to facilitate optimal vaccine delivery and accurate assessment of vaccine coverage. These data are also critical for research aimed at evaluating the new vaccine's safety and effectiveness. Systems used to collect immunization data include manual approaches in which data are collected and retained on paper, electronic systems in which data are captured on computer at the point of vaccination and hybrid systems which are comprised of both computerized and manual data collection components. This study's objective was to compare the efficiencies and perceptions of data collection methods employed during Canada's pandemic (H1N1) 2009 influenza vaccination campaign. A pan-Canadian observational study was conducted in a convenience sample of public health clinics and healthcare institutions during the H1N1 vaccination campaign in the fall of 2009. The study design consisted of three stages: Stage 1 involved passive observation of the site's layout, processes and client flow; Stage 2 entailed timing site staff on 20 clients through five core immunization tasks: i) client registration, ii) medical history collection, iii) medical history review, iv) vaccine administration record keeping and v) preparation of proof of vaccine administration for the client; in Stage 3, site staff completed a questionnaire regarding perceived usability of the site's data collection approach. Before the national study began, a pilot study was conducted in three seasonal influenza vaccination sites in Ontario, to both test that the proposed methodology was logistically feasible and to determine inter-rater reliability in the measurements of the research staff. Comparative analyses will be conducted across the range of data collection methods with respect to time required to collect immunization data, number and type of individual-level data elements collected, and clinic staff perceptions of the usability of the method employed at their site, using analysis of variance (ANOVA). Various data collection methods were employed at immunization sites across Canada during the pandemic (H1N1) 2009 influenza vaccination campaign. Our comparison of methods can facilitate planning an efficient, coordinated approach for collecting immunization data in future influenza seasons.

WHO consultation on Respiratory Syncytial Virus Vaccine Development Report from a World Health Organization Meeting held on 23-24 March 2015.

PubMed

Modjarrad, Kayvon; Giersing, Birgitte; Kaslow, David C; Smith, Peter G; Moorthy, Vasee S

2016-01-04

Respiratory syncytial virus (RSV) is a globally prevalent cause of lower respiratory infection in neonates and infants. Despite its disease burden, a safe and effective RSV vaccine has remained elusive. In recent years, improved understanding of RSV biology and innovations in immunogen design has resulted in the advancement of multiple vaccine candidates into the clinical development pipeline. Given the growing number of vaccines in clinical trials, the rapid pace at which they are being tested, and the likelihood that an RSV vaccine will reach the commercial market in the next 5-10 years, consensus and guidance on clinical development pathways and licensure routes are needed now, before large-scale efficacy trials commence. In pursuit of this aim, the World Health Organization convened the first RSV vaccine consultation in 15 years on the 23rd and 24th of March, 2015 in Geneva, Switzerland. The meeting's primary objective was to provide guidance on clinical endpoints and development pathways for vaccine trials with a focus on considerations of low- and middle-income countries. Meeting participants reached consensus on candidate case definitions for RSV disease, considerations for clinical efficacy endpoints, and the clinical development pathway for active and passive immunization trials in maternal and pediatric populations. The strategic focus of this meeting was on the development of high quality, safe and efficacious RSV preventive interventions for global use and included: (1) maternal/passive immunization to prevent RSV disease in infants less than 6 months; (2) pediatric immunization to prevent RSV disease in infants and young children once protection afforded by maternal immunization wanes. Copyright © 2015 World Health Organization; licensee Elsevier. Published by Elsevier Ltd.. All rights reserved.

Evaluation of a DNA Aβ42 vaccine in adult rhesus monkeys (Macaca mulatta): antibody kinetics and immune profile after intradermal immunization with full-length DNA Aβ42 trimer.

PubMed

Lambracht-Washington, Doris; Fu, Min; Frost, Pat; Rosenberg, Roger N

2017-04-26

Aggregated amyloid-β peptide 1-42 (Aβ42), derived from the cellular amyloid precursor protein, is one of the pathological hallmarks of Alzheimer's disease (AD). Although active immunization against Aβ42 peptide was successful in AD mouse models and led to removal of plaques and improved memory, a similar clinical trial in humans (Aβ42 peptide immunization with QS-21 adjuvant) was stopped in phase II, when 6% of the treated patients developed encephalitis. Currently ongoing passive immunizations with the injection of preformed monoclonal antibodies against different epitopes within the Aβ 1-42 peptide, which do not lead to activation of the immune system, have shown some effects in slowing AD pathology. Active DNA Aβ42 immunizations administered with the gene gun into the skin are noninflammatory because they activate a different T-cell population (Th2) with different cytokine responses eliciting a different humoral immune response. We present our findings in rhesus macaques that underwent the DNA Aβ42 immunization via gene gun delivery into the skin. Six rhesus monkeys received two different doses of a DNA Aβ42 trimer vaccine. The humoral immune response was analyzed from blood throughout the study, and cellular immune responses were determined in peripheral blood mononuclear cells (PBMCs) after three and six immunizations. DNA Aβ42 trimer immunization led to high titer antibody responses in the nonhuman primate (NHP) model. Antibodies generated in the rhesus monkeys following DNA Aβ42 immunization detected amyloid plaques consisting of human Aβ42 peptide in the brain of the triple-transgenic AD mouse model. T-cell responses showed no interferon (IFN)-γ- and interleukin (IL)-17-producing cells from PBMCs in Enzyme-Linked ImmunoSpot assays after three immunization time points. At six immunization time points, IFN-γ- and IL-17-producing cells were found in immunized animals as well as in control animals and were thus considered nonspecific and not due to the immunization regimen. IFN-γ and IL-17 secretion in response to Aβ42 peptide restimulation became undetectable after a 3-month rest period. Intradermal DNA Aβ42 immunization delivered with the gene gun produces a high antibody response in NHPs and is highly likely to be effective and safe in a clinical AD prevention trial in patients.

A Bivalent Heterologous DNA Virus-Like-Particle Prime-Boost Vaccine Elicits Broad Protection against both Group 1 and 2 Influenza A Viruses

PubMed Central

Jiang, Wenbo; Wang, Shuangshuang; Chen, Honglin; Ren, Huanhuan; Huang, Xun; Wang, Guiqin; Chen, Ling; Chen, Zhiwei

2017-01-01

ABSTRACT Current seasonal influenza vaccines are efficacious when vaccine strains are matched with circulating strains. However, they do not protect antigenic variants and newly emerging pandemic and outbreak strains. Thus, there is a critical need for developing so-called “universal” vaccines that protect against all influenza viruses. In the present study, we developed a bivalent heterologous DNA virus-like particle prime-boost vaccine strategy. We show that mice immunized with this vaccine were broadly protected against lethal challenge from group 1 (H1, H5, and H9) and group 2 (H3 and H7) viruses, with 94% aggregate survival. To determine the immune correlates of protection, we performed passive immunizations and in vitro assays. We show that this vaccine elicited antibody responses that bound HA from group 1 (H1, H2, H5, H6, H8, H9, H11, and H12) and group 2 (H3, H4, H7, H10, H14, and H15) and neutralized homologous and intrasubtypic H5 and H7 and heterosubtypic H1 viruses and hemagglutinin-specific CD4 and CD8 T cell responses. As a result, passive immunization with immune sera fully protected mice against H5, H7, and H1 challenge, whereas with both immune sera and T cells the mice survived heterosubtypic H3 and H9 challenge. Thus, it appears that (i) neutralizing antibodies alone fully protect against homologous and intrasubtypic H5 and H7 and (ii) neutralizing and binding antibodies are sufficient to protect against heterosubtypic H1, (iii) but against heterosubtypic H3 and H9, binding antibodies and T cells are required for complete survival. We believe that this vaccine regimen could potentially be a candidate for a “universal” influenza vaccine. IMPORTANCE Influenza virus infection is global health problem. Current seasonal influenza vaccines are efficacious only when vaccine strains are matched with circulating strains. However, these vaccines do not protect antigenic variants and newly emerging pandemic and outbreak strains. Because of this, there is an urgent need to develop so-called “universal” influenza vaccines that can protect against both current and future influenza strains. In the present study, we developed a bivalent heterologous prime-boost vaccine strategy. We show that a bivalent vaccine regimen elicited broad binding and neutralizing antibody and T cell responses that conferred broad protection against diverse challenge viruses in mice, suggesting that this bivalent prime-boost strategy could practically be a candidate for a “universal” influenza vaccine. PMID:28179535

Investigation of a panel of monoclonal antibodies and polyclonal sera against anthrax toxins resulted in identification of an anti-lethal factor antibody with disease-enhancing characteristics.

PubMed

Kulshreshtha, Parul; Tiwari, Ashutosh; Priyanka; Joon, Shikha; Sinha, Subrata; Bhatnagar, Rakesh

2015-12-01

Hybridomas were created using spleen of mice that were actively immunized with rLFn (recombinant N-terminal domain of lethal factor). Later on, separate group of mice were immunized with rLFn to obtain a polyclonal control for passive immunization studies of monoclonal antibodies. This led to the identification of one cohort of rLFn-immnized mice that harboured disease-enhancing polyclonal antibodies. At the same time, the monoclonal antibodies secreted by all the hybridomas were being tested. Two hybridomas secreted monoclonal antibodies (H10 and H8) that were cross-reactive with EF (edema factor) and LF (lethal factor), while the other two hybridomas secreted LF-specific antibodies (H7 and H11). Single chain variable fragment (LETscFv) was derived from H10 hybridoma. H11 was found to have disease-enhancing property. Combination of H11 with protective monoclonal antibodies (H8 and H10) reduced its disease enhancing nature. This in vitro abrogation of disease-enhancement provides the proof of concept that in polyclonal sera the disease enhancing character of a fraction of antibodies is overshadowed by the protective nature of the rest of the antibodies generated on active immunization. Copyright © 2015. Published by Elsevier Ltd.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peeters, S.H.; Carter, B.G.

An adoptive cell transfer system was defined for studying the long-term IgE anti-ovalbumin (OA) response of B6D2F/sub 1/ mice. The primary IgE anti-OA response given by this strain persisted for more than 8 months and the half-life of the IgE anti-OA in circulation was 10.5 hr as measured by residual passive cutaneous anaphylaxis (PCA) in rat skin. The system described for studying cell recruitment patterns in this response involves the transfer of primed spleen cells to irradiated recipients and the production in these recipients of IgE and hemagglutinating antibody without further overt antigenic challenge. The capacity of primed spleen cellsmore » to transfer the response was detectable 10 days after immunization and increased for the next 6 weeks. After this time the ability of primed cells to transfer the response declined steadily, but was still evident 8 months after immunization of the donor animals. The transferred response itself persisted in the recipients for many months.« less

The impact of dystocia on dairy calf health, welfare, performance and survival.

PubMed

Barrier, A C; Haskell, M J; Birch, S; Bagnall, A; Bell, D J; Dickinson, J; Macrae, A I; Dwyer, C M

2013-01-01

Up to one-third of dairy calves are born after dystocia and this is a major cause of calf mortality. This study investigated the neonatal physiology, survival, health and subsequent growth of dairy calves following dystocia and is the first longitudinal study to analyse multiple effects and to look beyond the perinatal period. A total of 455 live born Holstein calves (N: No assistance, n=360; FN: Farmer assistance but normally presented calf, n=82; FM: Farmer assistance of malpresented calf, n=13) were followed from birth to first service (heifers) or until leaving the farm (bulls). Compared to N calves, FN and FM animals had higher salivary cortisol concentrations at day 1 (P<0.001) and FN calves had lower passive immune transfer (P=0.03). Dystocia had no biologically significant impact on rectal temperature throughout the first 4 days (P>0.05). During the first 60 days, FM calves had a higher proportion of days with non-routine health treatments (P<0.05) and, by the time of weaning, mortality in FN and FM heifers was higher than in N calves (2.8×; P<0.01). However, in surviving calves, growth to first service was not affected by dystocia category (P>0.05). Calves which survive dystocia experience lower passive immunity transfer, higher mortality and higher indicators of physiological stress. Such calves have poorer welfare in the neonatal period and possibly beyond. Strategies need to be implemented to improve the subsequent health and welfare of such calves and to lower the incidence of dystocia. Copyright © 2012 Elsevier Ltd. All rights reserved.

Antibodies to the A27 protein of vaccinia virus neutralize and protect against infection but represent a minor component of Dryvax vaccine--induced immunity.

PubMed

He, Yong; Manischewitz, Jody; Meseda, Clement A; Merchlinsky, Michael; Vassell, Russell A; Sirota, Lev; Berkower, Ira; Golding, Hana; Weiss, Carol D

2007-10-01

The smallpox vaccine Dryvax, which consists of replication-competent vaccinia virus, elicits antibodies that play a major role in protection. Several vaccinia proteins generate neutralizing antibodies, but their importance for protection is unknown. We investigated the potency of antibodies to the A27 protein of the mature virion in neutralization and protection experiments and the contributions of A27 antibodies to Dryvax-induced immunity. Using a recombinant A27 protein (rA27), we confirmed that A27 contains neutralizing determinants and that vaccinia immune globulin (VIG) derived from Dryvax recipients contains reactivity to A27. However, VIG neutralization was not significantly reduced when A27 antibodies were removed, and antibodies elicited by an rA27 enhanced the protection conferred by VIG in passive transfer experiments. These findings demonstrate that A27 antibodies do not represent the major fraction of neutralizing activity in VIG and suggest that immunity may be augmented by vaccines and immune globulins that include strong antibody responses to A27.

Early-Onset Network Hyperexcitability in Presymptomatic Alzheimer’s Disease Transgenic Mice Is Suppressed by Passive Immunization with Anti-Human APP/Aβ Antibody and by mGluR5 Blockade

PubMed Central

Kazim, Syed F.; Chuang, Shih-Chieh; Zhao, Wangfa; Wong, Robert K. S.; Bianchi, Riccardo; Iqbal, Khalid

2017-01-01

Cortical and hippocampal network hyperexcitability appears to be an early event in Alzheimer’s disease (AD) pathogenesis, and may contribute to memory impairment. It remains unclear if network hyperexcitability precedes memory impairment in mouse models of AD and what are the underlying cellular mechanisms. We thus evaluated seizure susceptibility and hippocampal network hyperexcitability at ~3 weeks of age [prior to amyloid beta (Aβ) plaque deposition, neurofibrillary pathology, and cognitive impairment] in a triple transgenic mouse model of familial AD (3xTg-AD mouse) that harbors mutated human Aβ precursor protein (APP), tau and presenilin 1 (PS1) genes. Audiogenic seizures were elicited in a higher proportion of 3xTg-AD mice compared with wild type (WT) controls. Seizure susceptibility in 3xTg-AD mice was attenuated either by passive immunization with anti-human APP/Aβ antibody (6E10) or by blockade of metabotropic glutamate receptor 5 (mGluR5) with the selective antagonist, 2-methyl-6-(phenylethynyl)pyridine hydrochloride (MPEP). In in vitro hippocampal slices, suppression of synaptic inhibition with the GABAA receptor antagonist, bicuculline, induced prolonged epileptiform (>1.5 s in duration) ictal-like discharges in the CA3 neuronal network in the majority of the slices from 3xTg-AD mice. In contrast, only short epileptiform (<1.5 s in duration) interictal-like discharges were observed following bicuculline application in the CA3 region of WT slices. The ictal-like activity in CA3 region of the hippocampus was significantly reduced in the 6E10-immunized compared to the saline-treated 3xTg-AD mice. MPEP acutely suppressed the ictal-like discharges in 3xTg-AD slices. Remarkably, epileptiform discharge duration positively correlated with intraneuronal human (transgenic) APP/Aβ expression in the CA3 region of the hippocampus. Our data suggest that in a mouse model of familial AD, hypersynchronous network activity underlying seizure susceptibility precedes Aβ plaque pathology and memory impairment. This early-onset network hyperexcitability can be suppressed by passive immunization with an anti-human APP/Aβ antibody and by mGluR5 blockade in 3xTg-AD mice. PMID:28392767

Protection against canine parvovirus type 2 infection in puppies by colostrum-derived antibodies.

PubMed

Mila, Hanna; Grellet, Aurélien; Desario, Costantina; Feugier, Alexandre; Decaro, Nicola; Buonavoglia, Canio; Chastant-Maillard, Sylvie

2014-01-01

During the first weeks of life puppies remain protected against canine parvovirus type 2 (CPV2) infection thanks to maternally derived antibodies (MDA) absorbed with colostrum after birth. The objective of the present study was to present the variability in CPV2-specific passive immune transfer and its consequences in puppies naturally exposed to the parvovirus. Seventy-nine puppies from one breeding kennel were included in the study at birth and followed until 56 d of age. Once per week the MDA titre for CPV2 specific antibodies was determined in blood. Viral excretion was also evaluated on a rectal swab by CPV2 PCR assay and puppies were weighed to determine growth rate. At 2 d of age, thirty-four out of seventy-nine puppies (43 %) had MDA ≤1:160 (designed group A) and forty-five puppies (57 %) had greater MDA titres (designed group B). The level of absorbed maternal antibodies was shown to be associated with breed size and growth rate during the first 48 h of life. The MDA level declined with age in all cases; however, the proportion of puppies with the antibody level considered as protective against CPV2 infection was significantly higher in group B compared with A from day 2 until 42. Among all puppies surviving until 56 d of age, sixty-seven out of seventy (95·7 %) underwent CPV2 infection. However, puppies from group A excreted CPV2 significantly earlier than puppies from group B. The present study demonstrates the link between passive immune transfer, in terms of level of specific MDA absorbed, and length of the protection period against parvovirus infection in weaning puppies.

Development of the neonatal B and T cell repertoire in swine: implications for comparative and veterinary immunology.

PubMed

Butler, John E; Sinkora, Marek; Wertz, Nancy; Holtmeier, Wolfgang; Lemke, Caitlin D

2006-01-01

Birth in all higher vertebrates is at the center of the critical window of development in which newborns transition from dependence on innate immunity to dependence on their own adaptive immunity, with passive maternal immunity bridging this transition. Therefore we have studied immunological development through fetal and early neonatal life. In swine, B cells appear earlier in fetal development than T cells. B cell development begins in the yolk sac at the 20th day of gestation (DG20), progresses to fetal liver at DG30 and after DG45 continues in bone marrow. The first wave of developing T cells is gammadelta cells expressing a monomorphic Vdelta rearrangement. Thereafter, alphabeta T cells predominate and at birth, at least 19 TRBV subgroups are expressed, 17 of which appear highly homologous with those in humans. In contrast to the T cell repertoire and unlike humans and mice, the porcine pre-immune VH (IGHV-D-J) repertoire is highly restricted, depending primarily on CDR3 for diversity. The V-KAPPA (IGKV-J) repertoire and apparently also the V-LAMBDA (IGLV-J) repertoire, are also restricted. Diversification of the pre-immune B cell repertoire of swine and the ability to respond to both T-dependent and T-independent antigen depends on colonization of the gut after birth in which colonizing bacteria stimulate with Toll-like receptor ligands, especially bacterial DNA. This may explain the link between repertoire diversification and the anatomical location of primary lymphoid tissue like the ileal Peyers patches. Improper development of adaptive immunity can be caused by infectious agents like the porcine reproductive and respiratory syndrome virus that causes immune dysregulation resulting in immunological injury and autoimmunity.

In Vivo Imaging of Influenza Virus Infection in Immunized Mice

PubMed Central

Czakó, Rita; Vogel, Leatrice; Lamirande, Elaine W.; Bock, Kevin W.; Moore, Ian N.; Ellebedy, Ali H.; Ahmed, Rafi

2017-01-01

ABSTRACT Immunization is the cornerstone of seasonal influenza control and represents an important component of pandemic preparedness strategies. Using a bioluminescent reporter virus, we demonstrate the application of noninvasive in vivo imaging system (IVIS) technology to evaluate the preclinical efficacy of candidate vaccines and immunotherapy in a mouse model of influenza. Sequential imaging revealed distinct spatiotemporal kinetics of bioluminescence in groups of mice passively or actively immunized by various strategies that accelerated the clearance of the challenge virus at different rates and by distinct mechanisms. Imaging findings were consistent with conclusions derived from virus titers in the lungs and, notably, were more informative than conventional efficacy endpoints in some cases. Our findings demonstrate the reliability of IVIS as a qualitative approach to support preclinical evaluation of candidate medical countermeasures for influenza in mice. PMID:28559489

Role of T cell death in maintaining immune tolerance during persistent viral hepatitis.

PubMed

Larrubia, Juan Ramón; Lokhande, Megha Uttam; García-Garzón, Silvia; Miquel, Joaquín; Subirá, Dolores; Sanz-de-Villalobos, Eduardo

2013-03-28

Virus-specific T cells play an important role in the resolution of hepatic infection. However, during chronic hepatitis infection these cells lack their effector functions and fail to control the virus. Hepatitis B virus and hepatitis C virus have developed several mechanisms to generate immune tolerance. One of these strategies is the depletion of virus-specific T cells by apoptosis. The immunotolerogenic liver has unique property to retain and activate naïve T cell to avoid the over reactivation of immune response against antigens which is exploited by hepatotropic viruses to persist. The deletion of the virus-specific T cells occurs by intrinsic (passive) apoptotic mechanism. The pro-apoptotic molecule Bcl-2 interacting mediator (Bim) has attracted increasing attention as a pivotal involvement in apoptosis, as a regulator of tissue homeostasis and an enhancer for the viral persistence. Here, we reviewed our current knowledge on the evidence showing critical role of Bim in viral-specific T cell death by apoptotic pathways and helps in the immune tolerance.

Capture of lipopolysaccharide (endotoxin) by the blood clot: a comparative study.

PubMed

Armstrong, Margaret T; Rickles, Frederick R; Armstrong, Peter B

2013-01-01

In vertebrates and arthropods, blood clotting involves the establishment of a plug of aggregated thrombocytes (the cellular clot) and an extracellular fibrillar clot formed by the polymerization of the structural protein of the clot, which is fibrin in mammals, plasma lipoprotein in crustaceans, and coagulin in the horseshoe crab, Limulus polyphemus. Both elements of the clot function to staunch bleeding. Additionally, the extracellular clot functions as an agent of the innate immune system by providing a passive anti-microbial barrier and microbial entrapment device, which functions directly at the site of wounds to the integument. Here we show that, in addition to these passive functions in immunity, the plasma lipoprotein clot of lobster, the coagulin clot of Limulus, and both the platelet thrombus and the fibrin clot of mammals (human, mouse) operate to capture lipopolysaccharide (LPS, endotoxin). The lipid A core of LPS is the principal agent of gram-negative septicemia, which is responsible for more than 100,000 human deaths annually in the United States and is similarly toxic to arthropods. Quantification using the Limulus Amebocyte Lysate (LAL) test shows that clots capture significant quantities of LPS and fluorescent-labeled LPS can be seen by microscopy to decorate the clot fibrils. Thrombi generated in the living mouse accumulate LPS in vivo. It is suggested that capture of LPS released from gram-negative bacteria entrapped by the blood clot operates to protect against the disease that might be caused by its systemic dispersal.

Lack of passive transfer of renal tubulointerstitial disease by serum or monoclonal antibody specific for renal tubular antigens in the mouse.

PubMed

Evans, B D; Dilwith, R L; Balaban, S L; Rudofsky, U H

1988-01-01

Mice immunized with rabbit renal basement membranes form autoantibodies to their kidney glomerular and tubular basement membranes (GBM/TBM). Development of renal tubular disease (RTD) consists of deposition of autoantibodies along the GBM/TBM with the inter- and intratubular accumulation of lymphocytes and macrophages and destruction of the TBM. Transfer of this disease in mice with either serum or monoclonal antibodies, however, has been difficult to demonstrate and, therefore, attempts were made to confirm a report that RTD is passively transferred by anti-TBM autoantibodies. Using the revised protocol in this later report, we found that 12 weeks after transfer autoantibodies were deposited along the GBM and/or TBM of the recipients, yet RTD was not observed. Although qualitative and quantitative characteristics of the antibody may play a role in the pathogenesis in the murine model of RTD, we could not obtain evidence to support and confirm this study.

Novel Catanionic Surfactant Vesicle Vaccines Protect against Francisella tularensis LVS and Confer Significant Partial Protection against F. tularensis Schu S4 Strain

PubMed Central

Richard, Katharina; Mann, Barbara J.; Stocker, Lenea; Barry, Eileen M.; Qin, Aiping; Cole, Leah E.; Hurley, Matthew T.; Ernst, Robert K.; Michalek, Suzanne M.; Stein, Daniel C.; DeShong, Philip

2014-01-01

Francisella tularensis is a Gram-negative immune-evasive coccobacillus that causes tularemia in humans and animals. A safe and efficacious vaccine that is protective against multiple F. tularensis strains has yet to be developed. In this study, we tested a novel vaccine approach using artificial pathogens, synthetic nanoparticles made from catanionic surfactant vesicles that are functionalized by the incorporation of either F. tularensis type B live vaccine strain (F. tularensis LVS [LVS-V]) or F. tularensis type A Schu S4 strain (F. tularensis Schu S4 [Schu S4-V]) components. The immunization of C57BL/6 mice with “bare” vesicles, which did not express F. tularensis components, partially protected against F. tularensis LVS, presumably through activation of the innate immune response, and yet it failed to protect against the F. tularensis Schu S4 strain. In contrast, immunization with LVS-V fully protected mice against intraperitoneal (i.p.) F. tularensis LVS challenge, while immunization of mice with either LVS-V or Schu S4-V partially protected C57BL/6 mice against an intranasal (i.n.) F. tularensis Schu S4 challenge and significantly increased the mean time to death for nonsurvivors, particularly following the i.n. and heterologous (i.e., i.p./i.n.) routes of immunization. LVS-V immunization, but not immunization with empty vesicles, elicited high levels of IgG against nonlipopolysaccharide (non-LPS) epitopes that were increased after F. tularensis LVS challenge and significantly increased early cytokine production. Antisera from LVS-V-immunized mice conferred passive protection against challenge with F. tularensis LVS. Together, these data indicate that functionalized catanionic surfactant vesicles represent an important and novel tool for the development of a safe and effective F. tularensis subunit vaccine and may be applicable for use with other pathogens. PMID:24351755

CD14 and TLR4 are expressed early in tammar (Macropus eugenii) neonate development.

PubMed

Daly, Kerry A; Lefévre, Christophe; Nicholas, Kevin; Deane, Elizabeth; Williamson, Peter

2008-04-01

Marsupials are born in a relatively underdeveloped state and develop during a period of intensive maturation in the postnatal period. During this period, the young marsupial lacks a competent immune system, but manages to survive despite the potential of exposure to environmental pathogens. Passive immune transfer via the milk is one well-recognised strategy to compensate the neonate, but there also may be innate immune mechanisms in place. In this study, CD14 and Toll-like receptor 4 (TLR4), integral molecular components of pathogen recognition, were identified and characterised for the first time in a marsupial, the tammar wallaby (Macropus eugenii). Functional motifs of tammar CD14 and the toll/interleukin receptor (TIR) domain of TLR4 were highly conserved. The lipopolysaccharide (LPS) binding residues and the TLR4 interaction site of CD14 were conserved in all marsupials. The TIR signalling domain had 84% identity within marsupials and 77% with eutherians. Stimulation of adult tammar leukocytes resulted in the induction of a biphasic pattern of CD14 and TLR4 expression, and coincided with increased production of the pro-inflammatory cytokine TNF-alpha. Differential patterns of expression of CD14 and TLR4 were observed in tammar pouch young early in development, suggesting that early maturation of the innate immune system in these animals may have developed as an immune survival strategy to protect the marsupial neonate from exposure to microbial pathogens.

Tumor dormancy and cell signaling. II. Antibody as an agonist in inducing dormancy of a B cell lymphoma in SCID mice.

PubMed

Racila, E; Scheuermann, R H; Picker, L J; Yefenof, E; Tucker, T; Chang, W; Marches, R; Street, N E; Vitetta, E S; Uhr, J W

1995-04-01

Tumor dormancy can be induced in a murine B cell lymphoma (BCL1) by immunizing BALB/c mice with the tumor immunoglobulin (Ig) before tumor cell challenge. In this report, we have investigated the immunological and cellular mechanisms underlying the induction of dormancy. BCL1 tumor cells were injected into SCID mice passively immunized with antibody against different epitopes on IgM or IgD with or without idiotype (Id)-immune T lymphocytes. Results indicate that antibody to IgM is sufficient to induce a state of dormancy. Antibodies against other cell surface molecules including IgD and CD44 (Pgp1) had no effect on tumor growth. Id-immune T cells by themselves also had no effect on tumor growth in SCID mice. However, simultaneous transfer of anti-Id and Id-immune T cells enhanced both the induction and duration of the dormant state. In vitro studies indicated that antibody to IgM induced apoptosis within several hours and cell cycle arrest by 24 h. Hyper cross-linking increased apoptosis. The Fc gamma RII receptor played little or no role in the negative signaling. Antibodies that did not negatively signal in vitro did not induce dormancy in vivo. The results suggest that anti-IgM plays a decisive role in inducing tumor dormancy to BCL1 by acting as an agonist of IgM-mediated signal transduction pathways.

Controlling the burn and fueling the fire: defining the role for the alarmin interleukin-33 in alloimmunity.

PubMed

Liu, Quan; Turnquist, Heth R

2016-02-01

The purpose of this review is to provide a general update on recent developments in the immunobiology of IL-33 and IL-33-targeted immune cells. We also discuss emerging concepts regarding the potential role IL-33 appears to play in altering alloimmune responses mediating host-versus-graft and graft-versus-host alloresponses. Stromal cells and leukocytes display regulated expression of IL-33 and may actively or passively secrete this pleotropic cytokine. Type 2 innate lymphoid cells and a large proportion of tissue resident regulatory T cells (Treg) express membrane-bound suppressor of tumorigenicity 2 (ST2), the IL-33 receptor. Although Treg are appreciated suppressors of the inflammatory function of immune cells, both type 2 innate lymphoid cells and tissue resident Treg could play key roles in tissue repair and homeostasis. The functions of IL-33 in transplantation are poorly understood. However, like other disease models, the functions of IL-33 in alloimmunity appear to be quite pleiotropic. IL-33 is associated with immune regulation and graft protection in cardiac transplant settings. Yet, it is highly proinflammatory and stimulates lethal graft-versus-host disease through its capacity to stimulate type 1 immunity. Intensive studies on IL-33/ST2 signaling pathways and ST2 cell populations in solid organ and cell transplantation are warranted. A better understanding of this important pathway will provide promising therapeutic targets controlling pathogenic alloimmune responses, as well as potentially facilitating the function of regulatory and reparative immune cells posttransplantation.

AAVrh.10-Mediated Expression of an Anti-Cocaine Antibody Mediates Persistent Passive Immunization That Suppresses Cocaine-Induced Behavior

PubMed Central

Rosenberg, Jonathan B.; Hicks, Martin J.; De, Bishnu P.; Pagovich, Odelya; Frenk, Esther; Janda, Kim D.; Wee, Sunmee; Koob, George F.; Hackett, Neil R.; Kaminsky, Stephen M.; Worgall, Stefan; Tignor, Nicole; Mezey, Jason G.

2012-01-01

Abstract Cocaine addiction is a major problem affecting all societal and economic classes for which there is no effective therapy. We hypothesized an effective anti-cocaine vaccine could be developed by using an adeno-associated virus (AAV) gene transfer vector as the delivery vehicle to persistently express an anti-cocaine monoclonal antibody in vivo, which would sequester cocaine in the blood, preventing access to cognate receptors in the brain. To accomplish this, we constructed AAVrh.10antiCoc.Mab, an AAVrh.10 gene transfer vector expressing the heavy and light chains of the high affinity anti-cocaine monoclonal antibody GNC92H2. Intravenous administration of AAVrh.10antiCoc.Mab to mice mediated high, persistent serum levels of high-affinity, cocaine-specific antibodies that sequestered intravenously administered cocaine in the blood. With repeated intravenous cocaine challenge, naive mice exhibited hyperactivity, while the AAVrh.10antiCoc.Mab-vaccinated mice were completely resistant to the cocaine. These observations demonstrate a novel strategy for cocaine addiction by requiring only a single administration of an AAV vector mediating persistent, systemic anti-cocaine passive immunity. PMID:22486244

Parvovirus B19 Passive Transmission by Transfusion of Intercept® Blood System-Treated Platelet Concentrate

PubMed Central

Gowland, Peter; Fontana, Stefano; Stolz, Martin; Andina, Nicola; Niederhauser, Christoph

2016-01-01

Summary Background Pathogen reduction methods for blood components are effective for a large number of viruses though less against small, non-enveloped viruses such as Parvovirus B19 (B19V). This article describes the passive transmission by transfusion of two B19V-contaminated pooled platelet concentrates (PCs) which were treated with the Intercept® blood pathogen reduction system. Case Reports Two transfusion cases of B19V-contaminated Intercept-treated pooled PCs were described. Due to the analysis delay, the PCs were already transfused. The viral content of each donation was 4.87 × 1010 IU/ml in case 1and 1.46 × 108 IU/ml in case 2. B19V (52 IU/ml) was detected in the recipient of the case 1 PC, whereas no virus could be detected in the case 2 PC recipient. A B19V IgM response and a transient boost of the underlying B19V IgG immune status and was observed in recipient 1. Recipient of the case 2 PC remained B19V IgG- and IgM-negative. B19V DNA sequence and phylogenetic analysis revealed a 100% homology between donor and recipient. Conclusion This report describes passive B19V transmission by a PC with very high B19 viral load which elicited a transient boost of the B19V immunity, but not by a PC with a lower B19V content, suggesting that there is a B19 viral load threshold value at which B19V inactivation is exceeded. PMID:27403092

Passive Immunization with Milk Produced from an Immunized Cow Prevents Oral Recolonization by Streptococcus mutans

PubMed Central

Shimazaki, Yoshihiro; Mitoma, Morihide; Oho, Takahiko; Nakano, Yoshio; Yamashita, Yoshihisa; Okano, Kaoru; Nakano, Yutaka; Fukuyama, Masataka; Fujihara, Noboru; Nada, Youichi; Koga, Toshihiko

2001-01-01

Cell surface protein antigen (PAc) and water-insoluble glucan-synthesizing enzyme (GTF-I) produced by cariogenic Streptococcus mutans are two major factors implicated in the colonization of the human oral cavity by this bacterium. We examined the effect of bovine milk, produced after immunization with a fusion protein of functional domains of these proteins, on the recolonization of S. mutans. To prepare immune milk, a pregnant Holstein cow was immunized with the fusion protein PAcA-GB, a fusion of the saliva-binding alanine-rich region (PAcA) of PAc and the glucan-binding (GB) domain of GTF-I. After eight adult subjects received cetylpyridinium chloride (CPC) treatment, one subgroup (n = 4) rinsed their mouths with immune milk and a control group (n = 4) rinsed with nonimmune milk. S. mutans levels in saliva and dental plaque decreased after CPC treatment in both groups. Mouth rinsing with immune milk significantly inhibited recolonization of S. mutans in saliva and plaque. On the other hand, the numbers of S. mutans cells in saliva and plaque in the control group increased immediately after the CPC treatment and surpassed the baseline level 42 and 28 days, respectively, after the CPC treatment. The ratios of S. mutans to total streptococci in saliva and plaque in the group that received immune milk were lower than those in the control group. These results suggest that milk produced from immunized cow may be useful for controlling S. mutans in the human oral cavity. PMID:11687453

Impact of immune-metabolic interactions on age-related thymic demise and T cell senescence.

PubMed

Dixit, Vishwa Deep

2012-10-01

Emerging evidence indicates that the immune and metabolic interactions control several aspects of the aging process and associated chronic diseases. Among several sites of immune-metabolic interactions, thymic demise represents a particularly puzzling phenomenon because even in metabolically healthy middle-aged individuals the majority of thymic space is replaced with ectopic lipids. The new T cell specificities can only be generated in a functional thymus and, peripheral proliferation of pre-existing T cell clones provides limited immune-vigilance in the elderly. Therefore, it is hypothesized that the strategies that enhance thymic-lymphopoiesis may extend healthspan. Recent data suggest that byproducts of thymic fatty acids and lipids result in accumulation of 'lipotoxic DAMPs' (damage associated molecular patterns), which triggers the innate immune-sensing mechanism like inflammasome activation which links aging to thymic demise. The immune-metabolic interaction within the aging thymus produces a local pro-inflammatory state that directly compromises the thymic stromal microenvironment, thymic-lymphopoiesis and serves a precursor of systemic immune-dysregulation in the elderly. New evidence also suggests that ectopic thymic adipocytes may develop from specific intrathymic stromal cell precursors instead of a passive process that is simply a consequence of thymic lymphopenia. Thus the complex bidirectional interactions between metabolic and immune systems may link aging to health, T cell senescence, and associated diseases. This review discusses the immune-metabolic mechanisms during aging - with implications for developing future therapeutic strategies for living well beyond the expected. Copyright © 2012 Elsevier Ltd. All rights reserved.

Ricin-Holotoxin-Based Vaccines: Induction of Potent Ricin-Neutralizing Antibodies.

PubMed

Sabo, Tamar; Kronman, Chanoch; Mazor, Ohad

2016-01-01

Ricin is one of the most potent and lethal toxins known to which there is no available antidote. Currently, the most promising therapy is based on neutralizing antibodies elicited by active vaccination or given passively. Here, detailed protocols are provided for the production of two ricin holotoxin-based vaccines: monomerized subunit-based vaccine, and a formaldehyde-based ricin toxoid vaccine. Both vaccines were found to be stable with no toxic activity reversion even after long-term storage while eliciting high anti-ricin antibody titers possessing a potent neutralizing activity. The use of these vaccines is highly suitable for both the production of sera that can be used in passive protection experiments and immunization aimed to isolate potent anti-ricin monoclonal antibodies.

Immunotherapies to prevent mother-to-child transmission of HIV.

PubMed

Hicar, Mark D

2013-03-01

Although pharmacological interventions have been successful in reducing prevention of maternal to child transmission (PMTCT) of HIV, there is concern that complete elimination through this mode of transmission will require other measures. Immunotherapies in infants or pregnant mothers may be able to eradicate this form of transmission. A recent vaccine trial in adults showed encouraging results, but as in most HIV safety and efficacy vaccine trials, the question of MTCT was not addressed. Concentrating transmission studies and vaccine studies in the setting of MTCT offers several advantages. MTCT has a generally reproducible known transmission rate and has been successfully used to assess pharmacological interventions on decreasing transmission. Even in resource poor settings, the infrastructure for neonatal vaccination is already in place. Although rare, both passive and active vaccination trials have been successfully completed in pediatric populations. Unfortunately, little success in affecting MTCT has been shown. Largely, a correlate of protection in any type of transmission, including MTCT, is unknown. Data supports a role for antibodies in effecting strain and transmission during MTCT. The role of antibodies in MTCT is reviewed with a focus on recent passive immunization and considerations for future studies.

Effect of Chicken Egg Yolk Antibodies (IgY) against Diarrhea in Domesticated Animals: A Systematic Review and Meta-Analysis

PubMed Central

Diraviyam, Thirumalai; Zhao, Bin; Wang, Yuan; Schade, Ruediger; Michael, Antonysamy; Zhang, Xiaoying

2014-01-01

Background IgY antibodies are serum immunoglobulin in birds, reptiles and amphibians, and are transferred from serum to egg yolk to confer passive immunity to their embryos and offspring. Currently, the oral passive immunization using chicken IgY has been focused as an alternative to antibiotics for the treatment and control of diarrhea in animals and humans. This systematic review was focused to determine the effect of IgY in controlling and preventing diarrhea in domesticated animals including Piglets, Mice, Poultry and Calves. Methods and Results Previous research reports focused on treatment effect of Chicken IgY against diarrhea were retrieved from different electronic data bases (MEDLINE, EMBASE, SPRINGER-LINK, WILEY, AGRICOLA, MEDWELL Journals, Scientific Publish, Chinese articles from Core periodicals in 2012). A total of 61 studies in 4 different animal classes met the inclusion criteria. Data on study characteristics and outcome measures were extracted. The pooled relative risk (RR) of 49 studies of different animals [Piglets – 22; Mice – 14; Poultry – 7 and Calves – 6] in meta-analyses revealed that, IgY significantly reduced the risk of diarrhea in treatment group when compare to the placebo. However, the 95% confidence intervals of the majority of studies in animal class piglets and calves embrace RR of one. The same results were obtained in sub group analyses (treatment regiment – prophylactic or therapeutic; pathogen type – bacterial or viral). Perhaps, this inconsistency in the effect of IgY at the individual study level and overall effect measures could be influenced by the methodological heterogeneity. Conclusion The present systematic review (SR) and meta-analysis demonstrated the beneficial effect of IgY. This supports the opinion that IgY is useful for prophylaxis and treatment. However, more intensive studies using the gold standard animal experiments with the focus to use IgY alone or in combination with other alternative strategies are indispensable. PMID:24846286

Immunization in pregnancy.

PubMed

Gruslin, Andrée; Steben, Marc; Halperin, Scott; Money, Deborah M; Yudin, Mark H; Boucher, Marc; Cormier, Beatrice; Ogilvie, Gina; Paquet, Caroline; Steenbeek, Audrey; Van Eyk, Nancy; van Schalkwyk, Julie; Wong, Thomas

2008-12-01

To review the evidence and provide recommendations on immunization in pregnancy. Outcomes evaluated include effectiveness of immunization, and risks and benefits for mother and fetus. The Medline and Cochrane databases were searched for articles published up to June 2007 on the topic of immunization in pregnancy. The evidence obtained was reviewed and evaluated by the Infectious Diseases Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC) under the leadership of the principal authors, and recommendations were made according to guidelines developed by the Canadian Task Force on Preventive Health Care. Implementation of the recommendations in this guideline should result in more appropriate immunization of pregnant and breastfeeding women, decreased risk of contraindicated immunization, and better disease prevention. Recommendations 1. All women of childbearing age should be evaluated for the possibility of pregnancy before immunization. (III-A) 2. Health care providers should obtain an immunization history from all women accessing prenatal care. (III-A) 3. In general, live and/or live-attenuated virus vaccines are contraindicated during pregnancy, as there is a, largely theoretical, risk to the fetus. (II-3) 4. Women who have inadvertently received immunization with live or live-attenuated vaccines during pregnancy should not be counselled to terminate the pregnancy because of a teratogenic risk. (II-2) 5. Non-pregnant women immunized with a live or live-attenuated vaccine should be counselled to delay pregnancy for at least four weeks. (III) 6. Inactivated viral vaccines, bacterial vaccines, and toxoids are considered safe in pregnancy. (II-1) 7. Women who are breastfeeding can still be immunized (passive-active immunization, live or killed vaccines). (II-1) 8. Pregnant women should be offered the influenza vaccine when pregnant during the influenza season. (II-1).

Humoral immunity provides resident intestinal eosinophils access to luminal antigen via eosinophil-expressed low affinity Fc gamma receptors

PubMed Central

Smith, Kalmia M.; Rahman, Raiann S.; Spencer, Lisa A.

2016-01-01

Eosinophils are native to the healthy gastrointestinal tract, and are associated with inflammatory diseases likely triggered by exposure to food allergens (e.g. food allergies and eosinophilic gastrointestinal disorders). In models of allergic respiratory diseases and in vitro studies, direct antigen engagement elicits eosinophil effector functions including degranulation and antigen presentation. However, it was not known whether intestinal tissue eosinophils that are separated from luminal food antigens by a columnar epithelium might similarly engage food antigens. Using an intestinal ligated loop model in mice, here we determined that resident intestinal eosinophils acquire antigen from the lumen of antigen-sensitized but not naïve mice in vivo. Antigen acquisition was immunoglobulin-dependent; intestinal eosinophils were unable to acquire antigen in sensitized immunoglobulin-deficient mice, and passive immunization with immune serum or antigen-specific IgG was sufficient to enable intestinal eosinophils in otherwise naïve mice to acquire antigen in vivo. Intestinal eosinophils expressed low affinity IgG receptors, and the activating receptor FcγRIII was necessary for immunoglobulin-mediated acquisition of antigens by isolated intestinal eosinophils in vitro. Our combined data suggest that intestinal eosinophils acquire lumen-derived food antigens in sensitized mice via FcγRIII antigen focusing, and may therefore participate in antigen-driven secondary immune responses to oral antigens. PMID:27683752

Effect of Local Vibration and Passive Exercise on the Hormones and Neurotransmitters of Hypothalamic-Pituitary-Adrenal Axis in Hindlimb Unloading Rats

NASA Astrophysics Data System (ADS)

Luan, Huiqin; Huang, Yunfei; Li, Jian; Sun, Lianwen; Fan, Yubo

2018-04-01

Astronauts are severely affected by spaceflight-induced bone loss. Mechanical stimulation through exercise inhibits bone resorption and improves bone formation. Exercise and vibration can prevent the degeneration of the musculoskeletal system in tail-suspended rats, and long-term exercise stress will affect endocrine and immune systems that are prone to fatigue. However, the mechanisms through which exercise and vibration affect the endocrine system remain unknown. This study mainly aimed to investigate the changes in the contents of endocrine axis-related hormones and the effects of local vibration and passive exercise on hypothalamic-pituitary-adrenal (HPA) axis-related hormones in tail-suspended rats. A total of 32 Sprague-Dawley rats were randomly distributed into four groups (n = 8 per group): tail suspension (TS), TS + 35Hz vibration, TS + passive exercise, and control. The rats were placed on a passive exercise and local vibration regimen for 21 days. On day 22 of the experiment, the contents of corticotrophin-releasing hormone, adrenocorticotropic hormone, cortisol, and 5-hydroxytryptamine in the rats were quantified with kits in accordance with the manufacturer's instructions. Histomorphometry was applied to evaluate histological changes in the hypothalamus. Results showed that 35Hz local vibration cannot cause rats to remain in a stressed state and that it might not inhibit the function of the HPA axis. Therefore, we speculate that this local vibration intensity can protect the function of the HPA axis and helps tail-suspended rats to transition from stressed to adaptive state.

Co-administration of recombinant major envelope proteins (rA27L and rH3L) of buffalopox virus provides enhanced immunogenicity and protective efficacy in animal models.

PubMed

Kumar, Amit; Yogisharadhya, Revanaiah; Venkatesan, Gnanavel; Bhanuprakash, Veerakyathappa; Pandey, Awadh Bihari; Shivachandra, Sathish Bhadravati

2017-05-01

Buffalopox virus (BPXV) and other vaccinia-like viruses (VLVs) are causing an emerging/re-emerging zoonosis affecting buffaloes, cattle and humans in India and other countries. A27L and H3L are immuno-dominant major envelope proteins of intracellular mature virion (IMV) of orthopoxviruses (OPVs) and are highly conserved with an ability to elicit neutralizing antibodies. In the present study, two recombinant proteins namely; rA27L ( 21 S to E 110 ; ∼30 kDa) and rH3L( 1 M to I 280 ; ∼50 kDa) of BPXV-Vij/96 produced from Escherichia coli were used in vaccine formulation. A combined recombinant subunit vaccine comprising rA27L and rH3L antigens (10 μg of each) was used for active immunization of adult mice (20μg/dose/mice) with or without adjuvant (FCA/FIA) by intramuscular route. Immune responses revealed a gradual increase in antigen specific serum IgG as well as neutralizing antibody titers measured by using indirect-ELISA and serum neutralization test (SNT) respectively, which were higher as compared to that elicited by individual antigens. Suckling mice passively administered with combined anti-A27L and anti-H3L sera showed a complete (100%) pre-exposure protection upon challenge with virulent BPXV. Conclusively, this study highlights the potential utility of rA27L and rH3L proteins as safer candidate prophylactic antigens in combined recombinant subunit vaccine for buffalopox as well as passive protective efficacy of combined sera in employing better pre-exposure protection against virulent BPXV. Copyright © 2017 Elsevier B.V. All rights reserved.

Expulsion of Nippostrongylus brasiliensis from rats protected with serum. I. The efficacy of sera from singly and multiply infected donors related to time of administration and volume of serum injected.

PubMed Central

Miller, H R

1980-01-01

Several of the parameters related to the efficacy of passive protection against Nippostrongylus brasiliensis were studied in female hybrid (PVG/c x DA)F1 and outbred Wistar rats. The time after infection at which immune serum was given did, to some extent, alter the degree of protection conferred. There was substantial protection 8 days after challenge in rats given hyperimmune serum (HIS) either as daily injections 4-7 days post-infection or as a single dose on day 4. Eight separate experiments in which HIS was injected 4 days after challenge with 1000 l3 resulted in expulsion of 96 +/- 2% of the worm burdens by day 8. In a further six experiments, following infection with 2000 l3 and using the same protocol, 85 +/- 3% of the worm burden was expelled by day 8. A lag of 2 days between serum transfer and commencement of worm expulsion was consistently observed and, within the space of a further 2-4 days, more than 95% of the parasites were expelled. Transplanted 'normal' and 'damaged' adult worms were also susceptible to the passive transfer of HIS. Sera recovered from rats immunized with two or three challenges (hyperimmune sera) were more protective than sera from rats given one challenge. Serum from rats challenged for the first time 6 days previously conferred significant protection against a 1000 l3 infection and sera recovered 8 and 10-12 days post-infection with 4000 l3 protected recipients with increasing effectiveness. Thoracic duct lymph collected on the tenth day of infection with 4000 l3 was also protective. The response to both primary infection and hyperimmune serum was dose-dependent. The consistently good protection achieved in the present study when compared with the variable success of previous experiments (reviewed by Ogilvie & Jones, 1971) may be a function of the strain and sex of the rats used, together with modifications of the immunization protocols. The relevance of these findings to mucosal defences against N. brasiliensis is discussed. PMID:7429533

A human recombinant monoclonal antibody to cocaine: Preparation, characterization and behavioral studies

PubMed Central

Eubanks, Lisa M.; Ellis, Beverly A.; Cai, Xiaoqing; Schlosburg, Joel E.; Janda, Kim D.

2014-01-01

Cocaine abuse remains prevalent worldwide and continues to be a major health concern; nonetheless, there is no effective therapy. Immunopharmacothery has emerged as a promising treatment strategy by which anti-cocaine antibodies bind to the drug blunting its effects. Previous passive immunization studies using our human monoclonal antibody, GNCgzk, resulted in protection against cocaine overdose and acute toxicity. To further realize the clinical potential of this antibody, a recombinant IgG form of the antibody has been produced in mammalian cells. This antibody displayed a high binding affinity for cocaine (low nanomolar) in line with the superior attributes of the GNCgzk antibody and reduced cocaine-induced ataxia in a cocaine overdose model. PMID:25205191

Antibody treatment of human tumor xenografts elicits active anti-tumor immunity in nude mice

PubMed Central

Liebman, Meredith A.; Roche, Marly I.; Williams, Brent R.; Kim, Jae; Pageau, Steven C.; Sharon, Jacqueline

2007-01-01

Athymic nude mice bearing subcutaneous tumor xenografts of the human anti-colorectal cancer cell line SW480 were used as a preclinical model to explore anti-tumor immunotherapies. Intratumor or systemic treatment of the mice with murine anti-SW480 serum, recombinant anti-SW480 polyclonal antibodies, or the anti-colorectal cancer monoclonal antibody CO17-1A, caused retardation or regression of SW480 tumor xenografts. Interestingly, when mice that had regressed their tumors were re-challenged with SW480 cells, these mice regressed the new tumors without further antibody treatment. Adoptive transfer of spleen cells from mice that had regressed their tumors conferred anti-tumor immunity to naïve nude mice. Pilot experiments suggest that the transferred anti-tumor immunity is mediated by T cells of both γδ and αβ lineages. These results demonstrate that passive anti-tumor immunotherapy can elicit active immunity and support a role for extra-thymic γδ and αβ T cells in tumor rejection. Implications for potential immunotherapies include injection of tumor nodules in cancer patients with anti-tumor antibodies to induce anti-tumor T cell immunity. PMID:17920694

Perspectives on Immunoglobulins in Colostrum and Milk

PubMed Central

Hurley, Walter L.; Theil, Peter K.

2011-01-01

Immunoglobulins form an important component of the immunological activity found in milk and colostrum. They are central to the immunological link that occurs when the mother transfers passive immunity to the offspring. The mechanism of transfer varies among mammalian species. Cattle provide a readily available immune rich colostrum and milk in large quantities, making those secretions important potential sources of immune products that may benefit humans. Immune milk is a term used to describe a range of products of the bovine mammary gland that have been tested against several human diseases. The use of colostrum or milk as a source of immunoglobulins, whether intended for the neonate of the species producing the secretion or for a different species, can be viewed in the context of the types of immunoglobulins in the secretion, the mechanisms by which the immunoglobulins are secreted, and the mechanisms by which the neonate or adult consuming the milk then gains immunological benefit. The stability of immunoglobulins as they undergo processing in the milk, or undergo digestion in the intestine, is an additional consideration for evaluating the value of milk immunoglobulins. This review summarizes the fundamental knowledge of immunoglobulins found in colostrum, milk, and immune milk. PMID:22254105

Protective efficacy of a novel alpha hemolysin subunit vaccine (AT62) against Staphylococcus aureus skin and soft tissue infections.

PubMed

Adhikari, Rajan P; Thompson, Christopher D; Aman, M Javad; Lee, Jean C

2016-12-07

Alpha hemolysin (Hla) is a pore-forming toxin produced by most Staphylococcus aureus isolates. Hla is reported to play a key role in the pathogenesis of staphylococcal infections, such as skin and soft tissue infection, pneumonia, and lethal peritonitis. This study makes use of a novel recombinant subunit vaccine candidate (AT62) that was rationally designed based on the Hla heptameric crystal structure. AT62 comprises a critical structural domain at the N terminus of Hla, and it has no inherent toxic properties. We evaluated the efficacy of AT62 in protection against surgical wound infection and skin and soft tissue infection. Mice were vaccinated on days 0, 14, and 28 with 20μg AT62 or bovine serum albumin (BSA) mixed with Sigma adjuvant system®. Mice immunized with AT62 produced a robust antibody response against native Hla. In the surgical wound infection model, mice immunized with AT62 and challenged with a USA300 S. aureus strain showed a significantly reduced bacterial burden in the infected tissue compared to animals given BSA. Similarly, mice passively immunized with rabbit IgG to AT62 showed reduced wound infection and tissue damage. Subcutaneous abscess formation was not prevented by immunization with AT62. However, in a skin necrosis infection model, immunization with the AT62 vaccine resulted in smaller lesions and reduced mouse weight loss compared to controls. Although AT62 immunization reduced tissue necrosis, it did not reduce the bacterial burdens in the lesions compared to controls. Our data indicate that AT62 may be a valuable component of a multivalent vaccine against S. aureus. Copyright © 2016 Elsevier Ltd. All rights reserved.

Vaccination with Recombinant Non-transmembrane Domain of Protein Mannosyltransferase 4 Improves Survival during Murine Disseminated Candidiasis.

PubMed

Wang, Li; Yan, Lan; Li, Xing Xing; Xu, Guo Tong; An, Mao Mao; Jiang, Yuan Ying

2015-01-01

Candida albicans is the most common cause of invasive fungal infections in humans. The C. albicans cell wall proteins play an important role in crucial host-fungus interactions and might be ideal vaccine targets to induce protective immune response in host. Meanwhile, protein that is specific to C. albicans is also an ideal target of vaccine. In this study, 11 proteins involving cell wall biosynthesis, yeast-to-hypha formation, or specific to C. albicans were chosen and were successfully cloned, purified and verified. The immune protection of vaccination with each recombinant protein respectively in preventing systemic candidiasis in BALB/c mice was assessed. The injection of rPmt4p vaccination significantly increased survival rate, decreased fungal burdens in the heart, liver, brain, and kidneys, and increased serum levels of both immunoglobulin G (IgG) and IgM against rPmt4p in the immunized mice. Histopathological assessment demonstrated that rPmt4p vaccination protected the tissue structure, and decreased the infiltration of inflammatory cells. Passive transfer of the rPmt4p immunized serum increased survival rate against murine systemic candidiasis and significantly reduced organ fungal burden. The immune serum enhanced mouse neutrophil killing activity by directly neutralizing rPmt4p effects in vitro. Levels of interleukin (IL)-4, IL-10, IL-12p70, IL-17A and tumor necrosis factor (TNF)-α in serum were higher in the immunized mice compared to those in the adjuvant control group. In conclusion, our results suggested that rPmt4p vaccination may be considered as a potential vaccine candidate against systemic candidiasis.

A cross-reactive monoclonal antibody to nematode haemoglobin enhances protective immune responses to Nippostrongylus brasiliensis.

PubMed

Nieuwenhuizen, Natalie E; Meter, Jeanne M; Horsnell, William G; Hoving, J Claire; Fick, Lizette; Sharp, Michael F; Darby, Matthew G; Parihar, Suraj P; Brombacher, Frank; Lopata, Andreas L

2013-01-01

Nematode secreted haemoglobins have unusually high affinity for oxygen and possess nitric oxide deoxygenase, and catalase activity thought to be important in protection against host immune responses to infection. In this study, we generated a monoclonal antibody (48Eg) against haemoglobin of the nematode Anisakis pegreffii, and aimed to characterize cross-reactivity of 4E8g against haemoglobins of different nematodes and its potential to mediate protective immunity against a murine hookworm infection. Immunoprecipitation was used to isolate the 4E8g-binding antigen in Anisakis and Ascaris extracts, which were identified as haemoglobins by peptide mass fingerprinting and MS/MS. Immunological cross-reactivity was also demonstrated with haemoglobin of the rodent hookworm N. brasiliensis. Immunogenicity of nematode haemoglobin in mice and humans was tested by immunoblotting. Anisakis haemoglobin was recognized by IgG and IgE antibodies of Anisakis-infected mice, while Ascaris haemoglobin was recognized by IgG but not IgE antibodies in mouse and human sera. Sequencing of Anisakis haemoglobin revealed high similarity to haemoglobin of a related marine nematode, Psuedoterranova decipiens, which lacks the four -HKEE repeats of Ascaris haemoglobin important in octamer assembly. The localization of haemoglobin in the different parasites was examined by immunohistochemistry and associated with the excretory-secretary ducts in Anisakis, Ascaris and N. brasiliensis. Anisakis haemoglobin was strongly expressed in the L3 stage, unlike Ascaris haemoglobin, which is reportedly mainly expressed in adult worms. Passive immunization of mice with 4E8g prior to infection with N. brasiliensis enhanced protective Th2 immunity and led to a significant decrease in worm burdens. The monoclonal antibody 4E8g targets haemoglobin in broadly equivalent anatomical locations in parasitic nematodes and enhances host immunity to a hookworm infection.

The Immunology of Posttransplant CMV Infection: Potential Effect of CMV Immunoglobulins on Distinct Components of the Immune Response to CMV

PubMed Central

Carbone, Javier

2016-01-01

Abstract The immune response to cytomegalovirus (CMV) infection is highly complex, including humoral, cellular, innate, and adaptive immune responses. Detection of CMV by the innate immune system triggers production of type I IFNs and inflammatory cytokines which initiate cellular and humoral responses that are critical during the early viremic phase of CMV infection. Sustained control of CMV infection is largely accounted for by cellular immunity, involving various T-cell and B-cell subsets. In solid organ transplant patients, global suppression of innate and adaptive immunities by immunosuppressive agents limits immunological defense, including inhibition of natural killer cell activity with ongoing lowering of Ig levels and CMV-specific antibody titers. This is coupled with a short-term suppression of CMV-specific T cells, the extent and duration of which can predict risk of progression to CMV viremia. CMV immunoglobulin (CMVIG) preparations have the potential to exert immunomodulatory effects as well as providing passive immunization. Specific CMVIG antibodies and virus neutralization might be enhanced by modulation of dendritic cell activity and by a decrease in T-cell activation, effects which are of importance during the initial phase of infection. In summary, the role of CMVIG in reconstituting specific anti-CMV antibodies may be enhanced by some degree of modulation of the innate and adaptive immune responses, which could help to control some of the direct and indirect effects of CMV infection. PMID:26900990

The Immunology of Posttransplant CMV Infection: Potential Effect of CMV Immunoglobulins on Distinct Components of the Immune Response to CMV.

PubMed

Carbone, Javier

2016-03-01

The immune response to cytomegalovirus (CMV) infection is highly complex, including humoral, cellular, innate, and adaptive immune responses. Detection of CMV by the innate immune system triggers production of type I IFNs and inflammatory cytokines which initiate cellular and humoral responses that are critical during the early viremic phase of CMV infection. Sustained control of CMV infection is largely accounted for by cellular immunity, involving various T-cell and B-cell subsets. In solid organ transplant patients, global suppression of innate and adaptive immunities by immunosuppressive agents limits immunological defense, including inhibition of natural killer cell activity with ongoing lowering of Ig levels and CMV-specific antibody titers. This is coupled with a short-term suppression of CMV-specific T cells, the extent and duration of which can predict risk of progression to CMV viremia. CMV immunoglobulin (CMVIG) preparations have the potential to exert immunomodulatory effects as well as providing passive immunization. Specific CMVIG antibodies and virus neutralization might be enhanced by modulation of dendritic cell activity and by a decrease in T-cell activation, effects which are of importance during the initial phase of infection. In summary, the role of CMVIG in reconstituting specific anti-CMV antibodies may be enhanced by some degree of modulation of the innate and adaptive immune responses, which could help to control some of the direct and indirect effects of CMV infection.

Antibody Prophylaxis Against Dengue Virus 2 Infection in Non-Human Primates.

PubMed

Simmons, Monika; Putnak, Robert; Sun, Peifang; Burgess, Timothy; Marasco, Wayne A

2016-11-02

Passive immunization with anti-dengue virus (DENV) immune serum globulin (ISG) or monoclonal antibodies (Mabs) may serve to supplement or replace vaccination for short-term dengue immune prophylaxis. In the present study, we sought to establish proof-of-concept by evaluating several DENV-neutralizing antibodies for their ability to protect rhesus macaques against viremia following live virus challenge, including human anti-dengue ISG, and a human Mab (Mab11/wt) and its genetically engineered variant (Mab11/mutFc) that is unable to bind to cells with Fc gamma receptors (FcγR) and potentiate antibody-dependent enhancement (ADE). In the first experiment, groups of animals received ISG or Mab11/wt at low doses (3-10 mg/kg) or a saline control followed by challenge with DENV-2 at day 10 or 30. After passive immunization, only low-titered circulating virus-neutralizing antibody titers were measured in both groups, which were undetectable by day 30. After challenge at day 10, a reduction in viremia duration compared with the control was seen only in the ISG group (75%). However, after a day 30 challenge, no reduction in viremia was observed in both immunized groups. In a second experiment to test the effect of higher antibody doses on short-term protection, groups received either ISG, Mab11/wt, Mab11/mutFc (each at 25 mg/kg) or saline followed by challenge with DENV-2 on day 10. Increased virus-neutralizing antibody titers were detected in all groups at day 5 postinjection, with geometric mean titers (GMTs) of 464 (ISG), 313 (Mab11/wt), and 309 (Mab11/mutFc). After challenge, there was complete protection against viremia in the group that received ISG, and a reduction in viremia duration of 89% and 83% in groups that received Mab11/wt and Mab11/mutFc, respectively. An in vitro ADE assay in Fcγ receptor-bearing K562 cells with sera collected immediately before challenge showed increased DENV-2 infection levels in the presence of both ISG and Mab11/wt, which peaked at a serum dilution of 1:90, but not in Mab11/mutFc containing sera. The results suggest that antibody prophylaxis for dengue might be beneficial in eliminating or reducing viral loads thereby minimizing disease progression. Our results also suggest that blocking FcγR interactions through Mab11 Fc engineering may further prevent ADE. © The American Society of Tropical Medicine and Hygiene.

Formation and organization of protein domains in the immunological synapse

NASA Astrophysics Data System (ADS)

Carlson, Andreas; Mahadevan, L.

2014-11-01

The cellular basis for the adaptive immune response during antigen recognition relies on a specialized protein interface known as the immunological synapse. Here, we propose a minimal mathematical model for the dynamics of the IS that encompass membrane mechanics, hydrodynamics and protein kinetics. Simple scaling laws describe the dynamics of protein clusters as a function of membrane stiffness, rigidity of the adhesive proteins, and fluid flow in the synaptic cleft. Numerical simulations complement the scaling laws by quantifying the nucleation, growth and stabilization of proteins domains on the size of the cell. Direct comparison with experiment suggests that passive dynamics suffices to describe the short-time formation and organization of protein clusters, while the stabilization and long time dynamics of the synapse is likely determined by active cytoskeleton processes triggered by receptor binding. Our study reveals that the fluid flow generated by the interplay between membrane deformation and protein binding kinetics can assist immune cells in regulating protein sorting.

Sequential dengue virus infections detected in active and passive surveillance programs in Thailand, 1994-2010.

PubMed

Bhoomiboonchoo, Piraya; Nisalak, Ananda; Chansatiporn, Natkamol; Yoon, In-Kyu; Kalayanarooj, Siripen; Thipayamongkolgul, Mathuros; Endy, Timothy; Rothman, Alan L; Green, Sharone; Srikiatkhachorn, Anon; Buddhari, Darunee; Mammen, Mammen P; Gibbons, Robert V

2015-03-14

The effect of prior dengue virus (DENV) exposure on subsequent heterologous infection can be beneficial or detrimental depending on many factors including timing of infection. We sought to evaluate this effect by examining a large database of DENV infections captured by both active and passive surveillance encompassing a wide clinical spectrum of disease. We evaluated datasets from 17 years of hospital-based passive surveillance and nine years of cohort studies, including clinical and subclinical DENV infections, to assess the outcomes of sequential heterologous infections. Chi square or Fisher's exact test was used to compare proportions of infection outcomes such as disease severity; ANOVA was used for continuous variables. Multivariate logistic regression was used to assess risk factors for infection outcomes. Of 38,740 DENV infections, two or more infections were detected in 502 individuals; 14 had three infections. The mean ages at the time of the first and second detected infections were 7.6 ± 3.0 and 11.2 ± 3.0 years. The shortest time between sequential infections was 66 days. A longer time interval between sequential infections was associated with dengue hemorrhagic fever (DHF) in the second detected infection (OR 1.3, 95% CI 1.2-1.4). All possible sequential serotype pairs were observed among 201 subjects with DHF at the second detected infection, except DENV-4 followed by DENV-3. Among DENV infections detected in cohort subjects by active study surveillance and subsequent non-study hospital-based passive surveillance, hospitalization at the first detected infection increased the likelihood of hospitalization at the second detected infection. Increasing time between sequential DENV infections was associated with greater severity of the second detected infection, supporting the role of heterotypic immunity in both protection and enhancement. Hospitalization was positively associated between the first and second detected infections, suggesting a possible predisposition in some individuals to more severe dengue disease.

Immunization with recombinant bivalent chimera r-Cpae confers protection against alpha toxin and enterotoxin of Clostridium perfringens type A in murine model.

PubMed

Shreya, Das; Uppalapati, Siva R; Kingston, Joseph J; Sripathy, Murali H; Batra, Harsh V

2015-05-01

Clostridium perfringens type A, an anaerobic pathogen is the most potent cause of soft tissue infections like gas gangrene and enteric diseases like food poisoning and enteritis. The disease manifestations are mediated via two important exotoxins, viz. myonecrotic alpha toxin (αC) and enterotoxin (CPE). In the present study, we synthesized a bivalent chimeric protein r-Cpae comprising C-terminal binding regions of αC and CPE using structural vaccinology rationale and assessed its protective efficacy against both alpha toxin (αC) and enterotoxin (CPE) respectively, in murine model. Active immunization of mice with r-Cpae generated high circulating serum IgG (systemic), significantly increased intestinal mucosal s-IgA antibody titres and resulted in substantial protection to the immunized animals (100% and 75% survival) with reduced tissue morbidity when administered with 5×LD(100) doses of αC (intramuscular) and CPE (intra-gastric gavage) respectively. Mouse RBCs and Caco-2 cells incubated with a mixture of anti-r-Cpae antibodies and αC and CPE respectively, illustrated significantly higher protection against the respective toxins. Passive immunization of mice with a similar mixture resulted in 91-100% survival at the end of the 15 days observation period while mice immunized with a concoction of sham sera and respective toxins died within 2-3 days. This work demonstrates the efficacy of the rationally designed r-Cpae chimeric protein as a potential sub unit vaccine candidate against αC and CPE of C. perfringens type A toxemia. Copyright © 2015 Elsevier Ltd. All rights reserved.

Induction of protective and therapeutic antitumor immunity by a DNA vaccine with C3d as a molecular adjuvant.

PubMed

Xu, Gui-lian; Zhang, Ke-qin; Guo, Bo; Zhao, Ting-ting; Yang, Fei; Jiang, Man; Wang, Qing-hong; Shang, Yu-hang; Wu, Yu-zhang

2010-10-18

Although the critical role of complement component C3d as a molecular adjuvant in preventing virus infection is well established, its role in cancer therapies is unclear. In this study, we have engineered a DNA vaccine that expresses extracellular region of murine VEGFR-2 (FLK1(265-2493)) and 3 copies of C3d (C3d3), a component of complement as a molecular adjuvant, designed to increase antitumor immunity. VEGFR-2 has a more restricted expression on endothelial cells and is upregulated once these cells proliferate during angiogenesis in the tumor vasculature. Immunization of mice with vector encoding FLK1(265-2493) alone generated only background levels of anti-VEGFR-2 antibodies and slight inhibitory effect on tumor growth. However, the addition of C3d3 to the vaccine construct significantly augmented the anti-VEGFR-2 humoral immune response and inhibited the tumor growth. The antitumor activity induced by vaccination with vector encoding FLK1(265-2493)-C3d3 fusion protein was also demonstrated via growth inhibition of established tumors following passive transfer of immune serum from vaccinated mice. Our results suggest that vaccination with vector encoding FLK1(265-2493) with C3d3 as a molecular adjuvant induces adaptive humoral activity, which is directed against the murine VEGFR-2 and can significantly inhibit tumor growth, and that administration of C3d as a molecular adjuvant to increase antibodies levels to VEGFR-2 may provide an alternative treatment modality for cancer therapies. Copyright © 2010 Elsevier Ltd. All rights reserved.

Brainstem processing of vestibular sensory exafference: implications for motion sickness etiology

PubMed Central

Oman, Charles M.; Cullen, Kathleen E.

2014-01-01

The origin of the internal “sensory conflict” stimulus causing motion sickness has been debated for more than four decades. Recent studies show a subclass of neurons in the vestibular nuclei and deep cerebellar nuclei that respond preferentially to passive head movements. During active movement, the semicircular canal and otolith input (“reafference”) to these neurons is cancelled by a mechanism comparing the expected consequences of self-generated movement (estimated with an internal model-presumably located in the cerebellum) with the actual sensory feedback. The un-cancelled component (“exafference”) resulting from passive movement normally helps compensate for unexpected postural disturbances. Notably, the existence of such vestibular “sensory conflict” neurons had been postulated as early as 1982, but their existence and putative role in posture control, motion sickness has been long debated. Here we review the development of “sensory conflict” theories in relation to recent evidence for brainstem and cerebellar reafference cancellation, and identify some open research questions. We propose that conditions producing persistent activity of these neurons, or their targets, stimulates nearby brainstem emetic centers – via an as yet unidentified mechanism. We discuss how such a mechanism is consistent with the notable difference in motion sickness susceptibility of drivers as opposed to passengers, human immunity to normal self-generated movement, and why head restraint or lying horizontal confers relative immunity. Finally, we propose that fuller characterization of these mechanisms, and their potential role in motion sickness could lead to more effective, scientifically based prevention and treatment for motion sickness. PMID:24838552

Demonstration of antibodies to collagen and of collagen-anticollagen immune complexes in rheumatoid arthritis synovial fluids

PubMed Central

Menzel, J.; Steffen, C.; Kolarz, G.; Eberl, R.; Frank, O.; Thumb, N.

1976-01-01

Menzel, J., Steffen, C., Kolarz, G., Eberl, R., Frank, O., and Thumb, N. (1976).Annals of the Rheumatic Diseases, 35, 446-450. Demonstration of antibodies to collagen and of collagen-anticollagen immune complexes in rheumatoid arthritis synovial fluids. Twenty-nine synovial fluids from patients with rheumatoid arthritis (RA) and 10 synovial fluids from patients with other joint diseases were investigated with regard to the presence of antibodies to denatured human collagen and of collagen-anticollagen immune complexes. 12 of the 29 RA synovial fluids showed anticollagen titres from 1: 16 to 1: 512 in passive haemagglutination. Only one patient in the group with no arthritis had a significant anticollagen titre of 1: 32. Digestion of the synovial fluids with bacterial collagenase resulted in an anticollagen titre increase from two to four dilution steps in 9 of the RA fluids, while 6 previously negative RA synovial fluids showed anticollagen titres from 1: 32 to 1: 128 after digestion with collagenase. These results indicate the existence of collagen-anticollagen immune complexes in 15 of the 29 RA synovial fluids investigated. PMID:185972

Detoxified pneumolysin derivative Plym2 directly protects against pneumococcal infection via induction of inflammatory cytokines.

PubMed

Lu, Jingcai; Sun, Tianxu; Hou, Hongjia; Xu, Man; Gu, Tiejun; Dong, Yunliang; Wang, Dandan; Chen, Pinxu; Wu, Chunlai; Liang, Chunshu; Sun, Shiyang; Jiang, Chunlai; Kong, Wei; Wu, Yongge

2014-01-01

Streptococcus pneumoniae is a major cause of infectious disease and complications worldwide, such as pneumonia, otitis media, bacteremia and meningitis. New generation protein-based pneumococcal vaccines are recognized as alternative vaccine candidates. Pneumolysin (Ply) is a cholesterol-dependent cytolysin produced by all clinical isolates of S. pneumoniae. Our research group previously developed a highly detoxified Ply mutant designated Plym2 by replacement of two animo acids (C428G and W433F). Exhibiting undetectable levels of cytotoxicity, Plym2 could still elicit high titer neutralizing antibodies against the native toxin. However, evaluation of the active immunoprotective effects of Plym2 by subcutaneous immunization and lethal challenge with S. pneumoniae in mice did not yield favorable results. In the present work, we confirmed the previous observations by using passive immunization and systemic challenge. Results of the passive immunization were consistent with those of active immunization. Further experiments were conducted to explain the inability of high titer neutralizing antibodies against Ply to protect mice from S. pneumoniae challenge. Pneumococcal Ply is known to be the major factor responsible for the induction of inflammation that benefits the host. Proinflammatory cytokines facilitate the clearance of invaders by the recruitment and activation of leukocytes at the early infection stage. We demonstrated that Plym2 could induce proinflammatory cytokines similarly to wild-type Ply. A systemic infection model was used to clarify that Plym2 lacking cytolytic activity could protect mice from intraperitoneal challenge directly, while antibodies to the mutant had no effect. Therefore, the protective function of Plym2 may be due to its induction of proinflammatory cytokines. When used in the systemic infection model, Plym2 antibodies may block the induction of proinflammatory cytokines by Ply. These findings demonstrate that a Ply-based vaccine would not be an effective primary vaccine component, but it may be beneficial as an adjuvant to stimulate cytokine production.

PERCEPTIONS OF HIV AND PREVENTION EDUCATION AMONG INMATES OF ALABAMA PRISONS

PubMed Central

Ayanwale, Lekan; Moorer; Moorer, Ellis; Shaw, Habiba; Habtemariam, Tsegaye; Blackwell, Velma; Foster, Pamela; Findlay, Henry; Tameru, Berhanu; Nganwa, David; Ahmad, Anwar; Beyene, Gemechu; Robnett, Vinaida

2009-01-01

A 3-year interactive and passive training for HIV prevention education was conducted for 2,600 prisoners; 1,404 (54%) black, 1,092 (42%) white and 204 (4%) Hispanic. Less than 520 (20%) of inmates knew all the routes of HIV transmission. A post-presentation test showed that 96% became aware of HIV/AIDS transmission and can better protect themselves. Skin infections caused by Staphylococcus aereus were reported and manifested clinically as pustules, cellulites, boils, carbuncles or impetigo. Though no systemic infection was involved, staphylococcal infections suggest lowered immunity, an indicator to undiagnosed HIV. This study purposefully provides HIV prevention education model for prison health educators. PMID:20191111

Recurrent Cutaneous Herpes Simplex in Hairless Mice

PubMed Central

Underwood, Gerald E.; Weed, Sheldon D.

1974-01-01

Passively immunized hairless mice were inoculated cutaneously with herpes simplex virus. Thirty-nine days later, when the primary cutaneous lesions had completely healed, the mice were treated subcutaneously with prednisone. Within 12 to 30 days after starting prednisone treatment, herpesvirus was recovered by skin swabs from 12 of 71 (17%) of the treated mice. This new model has potential application for understanding and treating recurrent cutaneous herpes infections. PMID:4372171

New targeted therapies in pancreatic cancer.

PubMed

Seicean, Andrada; Petrusel, Livia; Seicean, Radu

2015-05-28

Patients with pancreatic cancer have a poor prognosis with a median survival of 4-6 mo and a 5-year survival of less than 5%. Despite therapy with gemcitabine, patient survival does not exceed 6 mo, likely due to natural resistance to gemcitabine. Therefore, it is hoped that more favorable results can be obtained by using guided immunotherapy against molecular targets. This review summarizes the new leading targeted therapies in pancreatic cancers, focusing on passive and specific immunotherapies. Passive immunotherapy may have a role for treatment in combination with radiochemotherapy, which otherwise destroys the immune system along with tumor cells. It includes mainly therapies targeting against kinases, including epidermal growth factor receptor, Ras/Raf/mitogen-activated protein kinase cascade, human epidermal growth factor receptor 2, insulin growth factor-1 receptor, phosphoinositide 3-kinase/Akt/mTOR and hepatocyte growth factor receptor. Therapies against DNA repair genes, histone deacetylases, microRNA, and pancreatic tumor tissue stromal elements (stromal extracellular matric and stromal pathways) are also discussed. Specific immunotherapies, such as vaccines (whole cell recombinant, peptide, and dendritic cell vaccines), adoptive cell therapy and immunotherapy targeting tumor stem cells, have the role of activating antitumor immune responses. In the future, treatments will likely include personalized medicine, tailored for numerous molecular therapeutic targets of multiple pathogenetic pathways.

Immunotherapy Approaches for Malignant Glioma From 2007 to 2009

PubMed Central

Sampson, John H.

2012-01-01

Malignant glioma is a deadly disease for which there have been few therapeutic advances over the past century. Although previous treatments were largely unsuccessful, glioma may be an ideal target for immune-based therapy. Recently, translational research led to several clinical trials based on tumor immunotherapy to treat patients with malignant glioma. Here we review 17 recent glioma immunotherapy clinical trials, published over the past 3 years. Various approaches were used, including passive transfer of naked and radiolabeled antibodies, tumor antigen-specific peptide immunization, and the use of patient tumor cells with or without dendritic cells as vaccines. We compare and discuss the current state of the art of clinical immunotherapy treatment, as well as its limited successes, pitfalls, and future potential. PMID:20424975

Effect of HIV Antibody VRC01 on Viral Rebound after Treatment Interruption

PubMed Central

Bar, K.J.; Sneller, M.C.; Harrison, L.J.; Justement, J.S.; Overton, E.T.; Petrone, M.E.; Salantes, D.B.; Seamon, C.A.; Scheinfeld, B.; Kwan, R.W.; Learn, G.H.; Proschan, M.A.; Kreider, E.F.; Blazkova, J.; Bardsley, M.; Refsland, E.W.; Messer, M.; Clarridge, K.E.; Tustin, N.B.; Madden, P.J.; Oden, K.S.; O’Dell, S.J.; Jarocki, B.; Shiakolas, A.R.; Tressler, R.L.; Doria-Rose, N.A.; Bailer, R.T.; Ledgerwood, J.E.; Capparelli, E.V.; Lynch, R.M.; Graham, B.S.; Moir, S.; Koup, R.A.; Mascola, J.R.; Hoxie, J.A.; Fauci, A.S.; Tebas, P.; Chun, T.-W.

2017-01-01

BACKGROUND The discovery of potent and broadly neutralizing antibodies (bNAbs) against human immunodeficiency virus (HIV) has made passive immunization a potential strategy for the prevention and treatment of HIV infection. We sought to determine whether passive administration of VRC01, a bNAb targeting the HIV CD4-binding site, can safely prevent or delay plasma viral rebound after the discontinuation of antiretroviral therapy (ART). METHODS We conducted two open-label trials (AIDS Clinical Trials Group [ACTG] A5340 and National Institutes of Health [NIH] 15-I-0140) of the safety, side-effect profile, pharmacokinetic properties, and antiviral activity of VRC01 in persons with HIV infection who were undergoing interruption of ART. RESULTS A total of 24 participants were enrolled, and one serious alcohol-related adverse event occurred. Viral rebound occurred despite plasma VRC01 concentrations greater than 50 μg per milliliter. The median time to rebound was 4 weeks in the A5340 trial and 5.6 weeks in the NIH trial. Study participants were more likely than historical controls to have viral suppression at week 4 (38% vs. 13%, P = 0.04 by a two-sided Fisher’s exact test in the A5340 trial; and 80% vs. 13%, P<0.001 by a two-sided Fisher’s exact test in the NIH trial) but the difference was not significant at week 8. Analyses of virus populations before ART as well as before and after ART interruption showed that VRC01 exerted pressure on rebounding virus, resulting in restriction of recrudescent viruses and selection for preexisting and emerging antibody neutralization–resistant virus. CONCLUSIONS VRC01 slightly delayed plasma viral rebound in the trial participants, as compared with historical controls, but it did not maintain viral suppression by week 8. In the small number of participants enrolled in these trials, no safety concerns were identified with passive immunization with a single bNAb (VRC01). (Funded by the National Institute of Allergy and Infectious Diseases and others; ACTG A5340 and NIH 15-I-0140 ClinicalTrials.gov numbers, NCT02463227 and NCT02471326.) PMID:27959728

Human rabies prevention--United States, 2008: recommendations of the Advisory Committee on Immunization Practices.

PubMed

Manning, Susan E; Rupprecht, Charles E; Fishbein, Daniel; Hanlon, Cathleen A; Lumlertdacha, Boonlert; Guerra, Marta; Meltzer, Martin I; Dhankhar, Praveen; Vaidya, Sagar A; Jenkins, Suzanne R; Sun, Benjamin; Hull, Harry F

2008-05-23

These recommendations of the Advisory Committee on Immunization Practices (ACIP) update the previous recommendations on human rabies prevention (CDC. Human rabies prevention--United States, 1999: recommendations of the Advisory Committee on Immunization Practices. MMWR 1999;48 [No. RR-1]) and reflect the status of rabies and antirabies biologics in the United States. This statement 1) provides updated information on human and animal rabies epidemiology; 2) summarizes the evidence regarding the effectiveness/efficacy, immunogenicity, and safety of rabies biologics; 3) presents new information on the cost-effectiveness of rabies postexposure prophylaxis; 4) presents recommendations for rabies postexposure and pre-exposure prophylaxis; and 5) presents information regarding treatment considerations for human rabies patients. These recommendations involve no substantial changes to the recommended approach for rabies postexposure or pre-exposure prophylaxis. ACIP recommends that prophylaxis for the prevention of rabies in humans exposed to rabies virus should include prompt and thorough wound cleansing followed by passive rabies immunization with human rabies immune globulin (HRIG) and vaccination with a cell culture rabies vaccine. For persons who have never been vaccinated against rabies, postexposure antirabies vaccination should always include administration of both passive antibody (HRIG) and vaccine (human diploid cell vaccine [HDCV] or purified chick embryo cell vaccine [PCECV]). Persons who have ever previously received complete vaccination regimens (pre-exposure or postexposure) with a cell culture vaccine or persons who have been vaccinated with other types of vaccines and have previously had a documented rabies virus neutralizing antibody titer should receive only 2 doses of vaccine: one on day 0 (as soon as the exposure is recognized and administration of vaccine can be arranged) and the second on day 3. HRIG is administered only once (i.e., at the beginning of antirabies prophylaxis) to previously unvaccinated persons to provide immediate, passive, rabies virus neutralizing antibody coverage until the patient responds to HDCV or PCECV by actively producing antibodies. A regimen of 5 1-mL doses of HDCV or PCECV should be administered intramuscularly to previously unvaccinated persons. The first dose of the 5-dose course should be administered as soon as possible after exposure (day 0). Additional doses should then be administered on days 3, 7, 14, and 28 after the first vaccination. Rabies pre-exposure vaccination should include three 1.0-mL injections of HDCV or PCECV administered intramuscularly (one injection per day on days 0, 7, and 21 or 28). Modifications were made to the language of the guidelines to clarify the recommendations and better specify the situations in which rabies post- and pre-exposure prophylaxis should be administered. No new rabies biologics are presented, and no changes were made to the vaccination schedules. However, rabies vaccine adsorbed (RVA, Bioport Corporation) is no longer available for rabies postexposure or pre-exposure prophylaxis, and intradermal pre-exposure prophylaxis is no longer recommended because it is not available in the United States.

Factors affecting the immunogenicity and potency of tetanus toxoid: implications for the elimination of neonatal and non-neonatal tetanus as public health problems.

PubMed Central

Dietz, V.; Galazka, A.; van Loon, F.; Cochi, S.

1997-01-01

An estimated 400,000 deaths occur annually from neonatal tetanus (NT). In 1989 WHO adopted the goal of eliminating NT as a public health problem worldwide. To achieve this, and to control non-neonatal tetanus (non-NT), WHO recommends that newborns be passively protected at birth by the antepartum administration of at least two doses of tetanus toxoid (TT) to their mothers and that all children subsequently receive at least three doses of diphtheria-tetanus-pertussis (DTP) vaccine. For this strategy to be effective, the TT used must be immunogenic. Potential factors that may affect TT immunogenicity need to be evaluated if NT is to be eliminated and if non-NT is to be controlled. Although data are conflicting, concurrent malarial infection may decrease the immune response to TT; however, malarial chemoprophylaxis may enhance the immune response. Malnutrition does not appear to affect immunogenicity; nevertheless, one study suggests that vitamin A deficiency is associated with an impaired immune response. Although it has been postulated that placental transfer of tetanus antibody is impaired in African women, a survey of the published literature suggests that this is not the case. Freezing TT has been shown to decrease its potency, but its impact on immunogenicity needs more evaluation. PMID:9141753

Evaluation of the protective efficacy of four novel identified membrane associated proteins of Streptococcus suis serotype 2.

PubMed

Zhou, Yang; Wang, Yan; Deng, Limei; Zheng, Chengkun; Yuan, Fangyan; Chen, Huanchun; Bei, Weicheng; Li, Jinquan

2015-05-05

Streptococcus suis serotype 2 (S. suis 2) is an important zoonotic pathogen that can also cause epidemics of life-threatening infections in humans. Surface proteins of pathogens play a critical role in the interaction with host system or environment, as they take part in processes like virulence, cytotoxicity, adhesion, signaling or transport, etc. Thus, surface proteins identified by the screening of immunoproteomic techniques are promising vaccine candidates or diagnostic markers. In this study, four membrane associated proteins (MAP) identified by immunoproteomic method were cloned and expressed as recombinant proteins with his-tag. Screening for vaccine candidates were firstly performed by protection assay in vivo and immunization with Sbp markedly protected mice against systemic S. suis 2 infection. The immune responses and protective of Sbp were further evaluated. The results showed that Sbp could elicit a strong humoral antibody response and protect mice from lethal challenge with S. suis 2. The antiserum against Sbp could efficiently impede survival of bacterial in whole blood killing assay and conferred significant protection against S. suis 2 infection in passive immunization assays. The findings indicate that Sbp may serve as an important factor in the pathogenesis of S. suis 2 and would be a promising subunit vaccine candidate. Copyright © 2015 Elsevier Ltd. All rights reserved.

Vaccination with Brucella abortus rough mutant RB51 protects BALB/c mice against virulent strains of Brucella abortus, Brucella melitensis, and Brucella ovis.

PubMed Central

Jiménez de Bagüés, M P; Elzer, P H; Jones, S M; Blasco, J M; Enright, F M; Schurig, G G; Winter, A J

1994-01-01

Vaccination of BALB/c mice with live Brucella abortus RB51, a stable rough mutant, produced protection against challenge with virulent strains of Brucella abortus, Brucella melitensis, and Brucella ovis. Passive-transfer experiments indicated that vaccinated mice were protected against B. abortus 2308 through cell-mediated immunity, against B. ovis PA through humoral immunity, and against B. melitensis 16M through both forms of immunity. Live bacteria were required for the induction of protective cell-mediated immunity; vaccination with whole killed cells of strain RB51 failed to protect mice against B. abortus 2308 despite development of good delayed-type hypersensitivity reactions. Protective antibodies against the heterologous species were generated in vaccinated mice primarily through anamnestic responses following challenge infections. Growth of the antigenically unrelated bacterium Listeria monocytogenes in the spleens of vaccinated mice indicated that nonspecific killing by residual activated macrophages contributed minimally to protection. These results encourage the continued investigation of strain RB51 as an alternative vaccine against heterologous Brucella species. However, its usefulness against B. ovis would be limited if, as suggested here, epitopes critical for protective cell-mediated immunity are not shared between B. abortus and B. ovis. Images PMID:7927779

Following Acute Encephalitis, Semliki Forest Virus is Undetectable in the Brain by Infectivity Assays but Functional Virus RNA Capable of Generating Infectious Virus Persists for Life.

PubMed

Fragkoudis, Rennos; Dixon-Ballany, Catherine M; Zagrajek, Adrian K; Kedzierski, Lukasz; Fazakerley, John K

2018-05-18

Alphaviruses are mosquito-transmitted RNA viruses which generally cause acute disease including mild febrile illness, rash, arthralgia, myalgia and more severely, encephalitis. In the mouse, peripheral infection with Semliki Forest virus (SFV) results in encephalitis. With non-virulent strains, infectious virus is detectable in the brain, by standard infectivity assays, for around ten days. As we have shown previously, in severe combined immunodeficient (SCID) mice, infectious virus is detectable for months in the brain. Here we show that in MHC-II -/- mice, with no functional CD4 T-cells, infectious virus is also detectable in the brain for long periods. In contrast, in the brains of CD8 -/- mice, virus RNA persists but infectious virus is not detectable. In SCID mice infected with SFV, repeated intraperitoneal administration of anti-SFV immune serum rapidly reduced the titer of infectious virus in the brain to undetectable, however virus RNA persisted. Repeated intraperitoneal passive transfer of immune serum resulted in maintenance of brain virus RNA, with no detectable infectious virus, for several weeks. When passive antibody transfer was stopped, antibody levels declined and infectious virus was again detectable in the brain. In aged immunocompetent mice, previously infected with SFV, immunosuppression of antibody responses many months after initial infection also resulted in renewed ability to detect infectious virus in the brain. In summary, antiviral antibodies control and determine whether infectious virus is detectable in the brain but immune responses cannot clear this infection from the brain. Functional virus RNA capable of generating infectious virus persists and if antibody levels decline, infectious virus is again detectable.

Morphological Characterization of Thioflavin-S-Positive Amyloid Plaques in Transgenic Alzheimer Mice and Effect of Passive Aβ Immunotherapy on Their Clearance

PubMed Central

Bussière, Thierry; Bard, Frédérique; Barbour, Robin; Grajeda, Henry; Guido, Terry; Khan, Karen; Schenk, Dale; Games, Dora; Seubert, Peter; Buttini, Manuel

2004-01-01

Transgenic mice mimicking certain features of Alzheimer’s disease (AD)-pathology, namely amyloid plaques and neurofibrillary tangles, have been developed in an effort to better understand the mechanism leading to the formation of these characteristic cerebral lesions. More recently, these animal models have been widely used to investigate emergent therapies aimed at the reduction of the cerebral amyloid load. Several studies have shown that immunotherapy targeting the amyloid peptide (Aβ) is efficacious at clearing the amyloid plaques or preventing their formation, and at reducing the memory/behavior impairment observed in these animals. In AD, different types of plaques likely have different pathogenic significance, and further characterization of plaque pathology in the PDAPP transgenic mice would enhance the evaluation of potential therapeutics. In the present study, a morphological classification of amyloid plaques present in the brains of PDAPP mice was established by using Thioflavin-S staining. Neuritic dystrophy associated with amyloid plaques was also investigated. Finally, the efficacy of passive immunization with anti-Aβ antibodies on the clearance of Thio-S positive amyloid plaques was studied. Our results show that distinct morphological types of plaques are differentially cleared depending upon the isotype of the antibody. PMID:15331422

Optical characteristics of natural waters protect amphibians from UV-B in the U.S. Pacific Northwest: a reply

USGS Publications Warehouse

Palen, Wendy J.; Schindler, Daniel E.; Adams, Michael J.; Pearl, Christopher A.; Bury, R. Bruce; Diamond, S.A.

2004-01-01

Nonimmune homing pigeons Columba livia were infected with the Jones' Barn strain of Trichomonas gallinae and subsequently transfused with plasma from acute or chronically infected pigeons harboring one of 3 different strains of T. gallinae. The transfusions were either a single 2 mi dose given one day after inoculation or three 1 ml doses given 0, 5, and 10 days after inoculation. Plasma from pigeons harboring any of the 3 strains was capable of passively immunizing nonimmune birds. All birds which were immunized with plasma from infected pigeons survived until killed at the end of the test period and no visceral lesions were found on necropsy but trichomonads were present in the oropharynx. All controls (untreated or transfused with normal plasma) died of visceral trichomoniasis. Immune plasma produced some lysis of trichomonads in vitro, and inhibition of motility and vacuolization occurred in some of the non-lysed organisms. The overall lytic activity in vitro affected less than 10% of the suspended trichomonads.

Detection of immune deposits in glomeruli: the masking effect on antigenicity of formalin in the presence of proteins.

PubMed

Hed, J; Eneström, S

1981-01-01

Formalin is known to mask the antigenicity of immune deposits in glomeruli but not of surface immunoglobulins of isolated lymphocytes. We have shown in mice with experimental passive anti-GBM glomerulonephritis that formalin masks the antigenicity of GBM-bound immunoglobulins only if the tissue is fixed before sectioning. The presence of a high concentration of normal bovine serum during fixation of cryostat sections masks the antigenicity of immune deposits, whereas formalin alone has no obvious effect. The same results were obtained with human immunoglobulins (IgG, IgM and IgA) bound to tissue sections. Protease treatment with pepsin and trypsin restored the ability of the immunoglobulins to be stained. The masking effect seems to be due to extensive cross-linking of environmental proteins which prevents fluorescent conjugates reaching their antigens. Methods for detecting immunoglobulins in tissues must, therefore, take into consideration the influence of fixatives not only on epitopes but also on the environment in which the antigenic determinants are localised.

Circulating Organ-Specific MicroRNAs Serve as Biomarkers in Organ-Specific Diseases: Implications for Organ Allo- and Xeno-Transplantation

PubMed Central

Zhou, Ming; Hara, Hidetaka; Dai, Yifan; Mou, Lisha; Cooper, David K. C.; Wu, Changyou; Cai, Zhiming

2016-01-01

Different cell types possess different miRNA expression profiles, and cell/tissue/organ-specific miRNAs (or profiles) indicate different diseases. Circulating miRNA is either actively secreted by living cells or passively released during cell death. Circulating cell/tissue/organ-specific miRNA may serve as a non-invasive biomarker for allo- or xeno-transplantation to monitor organ survival and immune rejection. In this review, we summarize the proof of concept that circulating organ-specific miRNAs serve as non-invasive biomarkers for a wide spectrum of clinical organ-specific manifestations such as liver-related disease, heart-related disease, kidney-related disease, and lung-related disease. Furthermore, we summarize how circulating organ-specific miRNAs may have advantages over conventional methods for monitoring immune rejection in organ transplantation. Finally, we discuss the implications and challenges of applying miRNA to monitor organ survival and immune rejection in allo- or xeno-transplantation. PMID:27490531

Oral Exposure to Phytomonas serpens Attenuates Thrombocytopenia and Leukopenia during Acute Infection with Trypanosoma cruzi

PubMed Central

da Silva, Rosiane V.; Malvezi, Aparecida D.; Augusto, Leonardo da Silva; Kian, Danielle; Tatakihara, Vera Lúcia H.; Yamauchi, Lucy M.; Yamada-Ogatta, Sueli F.; Rizzo, Luiz V.; Schenkman, Sergio; Pinge-Filho, Phileno

2013-01-01

Mice infected with Trypanosoma cruzi, the agent of Chagas disease, rapidly develop anemia and thrombocytopenia. These effects are partially promoted by the parasite trans-sialidase (TS), which is shed in the blood and depletes sialic acid from the platelets, inducing accelerated platelet clearance and causing thrombocytopenia during the acute phase of disease. Here, we demonstrate that oral immunization of C57BL/6 mice with Phytomonas serpens, a phytoflagellate parasite that shares common antigens with T. cruzi but has no TS activity, reduces parasite burden and prevents thrombocytopenia and leukopenia. Immunization also reduces platelet loss after intraperitoneal injection of TS. In addition, passive transfer of immune sera raised in mice against P. serpens prevented platelet clearance. Thus, oral exposure to P. serpens attenuates the progression of thrombocytopenia induced by TS from T. cruzi. These findings are not only important for the understanding of the pathogenesis of T. cruzi infection but also for developing novel approaches of intervention in Chagas disease. PMID:23844182

Oral exposure to Phytomonas serpens attenuates thrombocytopenia and leukopenia during acute infection with Trypanosoma cruzi.

PubMed

da Silva, Rosiane V; Malvezi, Aparecida D; Augusto, Leonardo da Silva; Kian, Danielle; Tatakihara, Vera Lúcia H; Yamauchi, Lucy M; Yamada-Ogatta, Sueli F; Rizzo, Luiz V; Schenkman, Sergio; Pinge-Filho, Phileno

2013-01-01

Mice infected with Trypanosoma cruzi, the agent of Chagas disease, rapidly develop anemia and thrombocytopenia. These effects are partially promoted by the parasite trans-sialidase (TS), which is shed in the blood and depletes sialic acid from the platelets, inducing accelerated platelet clearance and causing thrombocytopenia during the acute phase of disease. Here, we demonstrate that oral immunization of C57BL/6 mice with Phytomonas serpens, a phytoflagellate parasite that shares common antigens with T. cruzi but has no TS activity, reduces parasite burden and prevents thrombocytopenia and leukopenia. Immunization also reduces platelet loss after intraperitoneal injection of TS. In addition, passive transfer of immune sera raised in mice against P. serpens prevented platelet clearance. Thus, oral exposure to P. serpens attenuates the progression of thrombocytopenia induced by TS from T. cruzi. These findings are not only important for the understanding of the pathogenesis of T. cruzi infection but also for developing novel approaches of intervention in Chagas disease.

CD8+ T cells produce a dialyzable antigen-specific activator of dendritic cells

PubMed Central

Myles, Ian A.; Zhao, Ming; Nardone, Glenn; Olano, Lisa R.; Reckhow, Jensen D.; Saleem, Danial; Break, Timothy J.; Lionakis, Michail S.; Myers, Timothy G.; Gardina, Paul J.; Kirkpatrick, Charles H.; Holland, Steven M.; Datta, Sandip K.

2017-01-01

Cellular lysates from PPD+ donors have been reported to transfer tuberculin reactivity to naïve recipients, but not diphtheria reactivity, and vice versa. A historically controversial topic, the terms "transfer factor" and "DLE" were used to characterize the reactivity-transferring properties of lysates. Intrigued by these reported phenomena, we found that the cellular extract derived from antigen-specific memory CD8+ T cells induces IL-6 from antigen-matched APCs. This ultimately elicits IL-17 from bystander memory CD8+ T cells. We have identified that dialyzable peptide sequences, S100a9, and the TCR β chain from CD8+ T cells contribute to the molecular nature of this activity. We further show that extracts from antigen-targeted T cells enhance immunity to Staphylococcus aureus and Candida albicans. These effects are sensitive to immunization protocols and extraction methodology in ways that may explain past discrepancies in the reproducibility of passive cellular immunity. PMID:27515950

Combined Active Humoral and Cellular Immunization Approaches for the Treatment of Synucleinopathies.

PubMed

Rockenstein, Edward; Ostroff, Gary; Dikengil, Fusun; Rus, Florentina; Mante, Michael; Florio, Jazmin; Adame, Anthony; Trinh, Ivy; Kim, Changyoun; Overk, Cassia; Masliah, Eliezer; Rissman, Robert A

2018-01-24

Dementia with Lewy bodies, Parkinson's disease, and Multiple System Atrophy are age-related neurodegenerative disorders characterized by progressive accumulation of α-synuclein (α-syn) and jointly termed synucleinopathies. Currently, no disease-modifying treatments are available for these disorders. Previous preclinical studies demonstrate that active and passive immunizations targeting α-syn partially ameliorate behavioral deficits and α-syn accumulation; however, it is unknown whether combining humoral and cellular immunization might act synergistically to reduce inflammation and improve microglial-mediated α-syn clearance. Since combined delivery of antigen plus rapamycin (RAP) in nanoparticles is known to induce antigen-specific regulatory T cells (Tregs), we adapted this approach to α-syn using the antigen-presenting cell-targeting glucan microparticle (GP) vaccine delivery system. PDGF-α-syn transgenic (tg) male and female mice were immunized with GP-alone, GP-α-syn (active humoral immunization), GP+RAP, or GP+RAP/α-syn (combined active humoral and Treg) and analyzed using neuropathological and biochemical markers. Active immunization resulted in higher serological total IgG, IgG1, and IgG2a anti-α-syn levels. Compared with mice immunized with GP-alone or GP-α-syn, mice vaccinated with GP+RAP or GP+RAP/α-syn displayed increased numbers of CD25-, FoxP3-, and CD4-positive cells in the CNS. GP-α-syn or GP+RAP/α-syn immunizations resulted in a 30-45% reduction in α-syn accumulation, neuroinflammation, and neurodegeneration. Mice immunized with GP+RAP/α-syn further rescued neurons and reduced neuroinflammation. Levels of TGF-β1 were increased with GP+RAP/α-syn immunization, while levels of TNF-α and IL-6 were reduced. We conclude that the observed effects of GP+RAP/α-syn immunization support the hypothesis that cellular immunization may enhance the effects of active immunotherapy for the treatment of synucleinopathies. SIGNIFICANCE STATEMENT We show that a novel vaccination modality combining an antigen-presenting cell-targeting glucan particle (GP) vaccine delivery system with encapsulated antigen (α-synuclein) + rapamycin (RAP) induced both strong anti-α-synuclein antibody titers and regulatory T cells (Tregs). This vaccine, collectively termed GP+RAP/α-syn, is capable of triggering neuroprotective Treg responses in synucleinopathy models, and the combined vaccine is more effective than the humoral or cellular immunization alone. Together, these results support the further development of this multifunctional vaccine approach for the treatment of synucleinopathies, such as Parkinson's disease, dementia with Lewy bodies, and multiple systems atrophy. Copyright © 2018 the authors 0270-6474/18/381000-15$15.00/0.

Impact of maternally derived immunity on piglets' immune response and protection against porcine circovirus type 2 (PCV2) after vaccination against PCV2 at different age.

PubMed

Martelli, Paolo; Saleri, Roberta; Ferrarini, Giulia; De Angelis, Elena; Cavalli, Valeria; Benetti, Michele; Ferrari, Luca; Canelli, Elena; Bonilauri, Paolo; Arioli, Elena; Caleffi, Antonio; Nathues, Heiko; Borghetti, Paolo

2016-05-11

This study was aimed at evaluating the clinical protection, the level of Porcine circovirus type 2 (PCV2) viremia and the immune response (antibodies and IFN-γ secreting cells (SC)) in piglets derived from PCV2 vaccinated sows and themselves vaccinated against PCV2 at different age, namely at 4, 6 and 8 weeks. The cohort study has been carried out over three subsequent production cycles (replicates). At the start/enrolment, 46 gilts were considered at first mating, bled and vaccinated. At the first, second and third farrowing, dams were bled and re-vaccinated at the subsequent mating after weaning piglets. Overall 400 piglets at each farrowing (first, second and third) were randomly allocated in three different groups (100 piglets/group) based on the timing of vaccination (4, 6 or 8 weeks of age). A fourth group was kept non-vaccinated (controls). Piglets were vaccinated intramuscularly with one dose (2 mL) of a commercial PCV2a-based subunit vaccine (Porcilis® PCV). Twenty animals per group were bled at weaning and from vaccination to slaughter every 4 weeks for the detection of PCV2 viremia, humoral and cell-mediated immune responses. Clinical signs and individual treatments (morbidity), mortality, and body weight of all piglets were recorded. All vaccination schemes (4, 6 and 8 weeks of age) were able to induce an antibody response and IFN-γ SC. The highest clinical and virological protection sustained by immune reactivity was observed in pigs vaccinated at 6 weeks of age. Overall, repeated PCV2 vaccination in sows at mating and the subsequent higher levels of maternally derived antibodies did not significantly interfere with the induction of both humoral and cell-mediated immunity in their piglets after vaccination. The combination of vaccination in sows at mating and in piglets at 6 weeks of age was more effective for controlling PCV2 natural infection, than other vaccination schemas, thus sustaining that some interference of MDA with the induction of an efficient immune response could be considered. In conclusion, optimal vaccination strategy needs to balance the levels of passive immunity, the management practices and timing of infection.

Treatment with proteolytic enzymes decreases glomerular immune complex deposits in passive serum sickness in rats and mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Emancipator, S.N.; Nakazawa, M.; Lamm, M.E.

1986-03-05

This study assessed the effect of protease treatment on glomerular immune complex (IC) deposition in passive serum sickness. IC containing 2.2 mg of specific rabbit antibovine gammaglobulin (Ab) and cationic bovine gammaglobulin (CBGG) at 5-fold antigen excess were given via tail vein to 140 g Sprague-Dawley rats; some rats received IC containing /sup 125/I-Ab. After maximal glomerular IC deposition (1h) a single intravenous dose of either 4 mg chymopapain plus 2 mg subtilisin (T), or saline (C) was given. By immunofluorescence (IF) 1 h later, 1/13 T rats had bright capillary wall deposits of CBGG vs 10/11 C rats (x/supmore » 2/ = 13.4, p < .001); 6/13 T rats had Ab vs. 10/11 C rats (x/sup 2/ = 4.05, p < .05). Isolated glomeruli from T rats given /sup 125/I-IC had 25% less Ab (3267 +/- 293 cpm/mg glomerular protein) than C rats (4327 +/- 530, p < .005). 20 g BALB/c mice given IC with CBGG and 0.3 mg Ab, or IC with native BGG (nBGG) and 1 mg Ab via tail vein received 0.5 mg chymopapain and 0.25 mg subtilisin in 5 divided intraperitoneal doses q 10 min beginning 1 h later. 20 min after the last dose, 2/15 T mice given CBGG-IC had capillary wall Ab deposits by IF vs 13/16 C mice (x/sup 2/ = 11.7, p < .001). 1/16 T mice given nBGG-IC had mesangial Ab deposits vs. 11/15 C mice (x/sup 2/ = 10.8, p < .001). The authors conclude that protease treatment can remove glomerular IC deposits.« less

Vaccination against nicotine alters the distribution of nicotine delivered via cigarette smoke inhalation to rats

PubMed Central

Pravetoni, M; Keyler, DE; Raleigh, MD; Harris, AC; LeSage, MG; Mattson, CK; Pettersson, S; Pentel, PR

2011-01-01

Preclinical models of nicotine vaccine pharmacology have relied on i.v. or s.c. administration of nicotine. Models using cigarette smoke inhalation might more accurately simulate nicotine exposure in smokers. Nicotine vaccine effects were examined in rats using two cigarette smoke exposure models: a 10 minute nose-only exposure (NSE) producing serum nicotine levels equivalent to the nicotine boost from 1 cigarette in a smoker, and a two hour whole-body exposure (WBE) producing serum nicotine levels similar to those associated with regular midday smoking. Vaccination prior to 10 min smoke NSE reduced nicotine distribution to brain by 90%, comparable to its effect on nicotine administered i.v. Vaccination prior to 2 hr smoke WBE reduced nicotine distribution to brain by 35%. The nicotine concentration in broncheoalveolar lavage (BAL) fluid obtained after 2 hr WBE was increased by 230% in vaccinated rats but was also increased in rats passively immunized with a nicotine-specific monoclonal antibody, and so was likely due to transfer of antibody from serum rather than local production at the pulmonary mucosa. Nicotine-specific IgA was not detectable in BAL fluid, but titers in serum were appreciable at 21–25% of the IgG titer and could contribute to vaccine efficacy. Both vaccination and passive immunization are effective in reducing nicotine distribution to brain in rats when nicotine is delivered via inhaled cigarette smoke. These data validate results previously obtained in rodents for nicotine vaccines using i.v. or s.c. nicotine dosing and provide a quantitative method for studying aspects of nicotine exposure which are unique to cigarette smoke inhalation. PMID:21333633

Evaluation of five commercially available assays and measurement of serum total protein concentration via refractometry for the diagnosis of failure of passive transfer of immunity in foals.

PubMed

Davis, Rachel; Giguère, Steeve

2005-11-15

To determine and compare sensitivity, specificity, accuracy, and predictive values of measurement of serum total protein concentration by refractometry as well as 5 commercially available kits for the diagnosis of failure of passive transfer (FPT) of immunity in foals. Prospective study. 65 foals with various medical problems and 35 clinically normal foals. IgG concentration in serum was assessed by use of zinc sulfate turbidity (assay C), glutaraldehyde coagulation (assay D), 2 semiquantitative immunoassays (assays F and G), and a quantitative immunoassay (assay H). Serum total protein concentration was assessed by refractometry. Radial immunodiffusion (assays A and B) was used as the reference method. For detection of IgG < 400 mg/dL, sensitivity of assay H (100%) was not significantly different from that of assays C, E, and G (88.9%). Specificity of assays H (96.0%) and G (95.8%) was significantly higher than that of assays C (79.4%) and E (78.1 %). For detection of IgG < 800 mg/dL, sensitivities of assays H (976%), D (92.9%), C (81.0%), and G (81.0%) were significantly higher than that of assay F (52.4%). Specificity of assays F (100%), G (94.7%), and H (82.8%) was significantly higher than that of assays C (56.9%) and D (58.6%). Serum total protein concentration < or = 4.5 g/dL was suggestive of FPT, whereas values > or = 6.0 g/dL indicated adequate IgG concentrations. Most assays were adequate as initial screening tests. However, their use as a definitive test would result in unnecessary treatment of foals with adequate IgG concentrations.

Optical Sensors for Use in Propulsion Control Systems

NASA Technical Reports Server (NTRS)

Fritsch, Klaus

1997-01-01

This final technical report describes the results of a cooperative effort which was originally established between John Carroll University and the Instrumentation and Control Technology Division at NASA Lewis Research Center on November, 1982, and then continued with the Engine Sensor Technology Branch at NASA Lewis until March, 1995. All work at John Carroll University was directed by the principal investigator of this grant, Klaus Fritsch, Ph.D. For the first two years of this grant this effort was supervised at NASA by Mr. Robert J. Baumbick and for the remainder of the grant by Dr. Glenn M. Beheim. All research was carried out in close cooperation with Dr. Beheim. Electrically passive optical sensors for measurands such as pressure, temperature, position, and rotational speed are required for aircraft engine control in fly-by-light digital aircraft control systems. Fiberoptic data links and optical multiplexing techniques should be used for combining and processing the outputs from several sensors, sharing as many optical end electronic parts as possible. The overall objective of this grant was to explore techniques for designing and constructing such electrically passive optical sensors for measuring physical parameters in jet aircraft engines and for use in aircraft control systems. We have concentrated our efforts on pressure, temperature, and position sensors employing techniques which are relatively immune to transmissivity variations of the fiber links and to variations in intensity of the light source. Infrared light-emitting diodes are employed because of their longevity and immunity to vibration. We have also studied a number of multiplexing techniques. On the following pages I will give thumbnail sketches of the projects carried out under this grant and provide references to publications and John Carroll M.S. theses which resulted directly from this work and which describe these projects in greater detail.

Efficacy of hydrodynamic interleukin 10 gene transfer in human liver segments with interest in transplantation.

PubMed

Sendra Gisbert, Luis; Miguel Matas, Antonio; Sabater Ortí, Luis; Herrero, María José; Sabater Olivas, Laura; Montalvá Orón, Eva María; Frasson, Matteo; Abargues López, Rafael; López-Andújar, Rafael; García-Granero Ximénez, Eduardo; Aliño Pellicer, Salvador Francisco

2017-01-01

Different diseases lead, during their advanced stages, to chronic or acute liver failure, whose unique treatment consists in organ transplantation. The success of intervention is limited by host immune response and graft rejection. The use of immunosuppressant drugs generally improve organ transplantation, but they cannot completely solve the problem. Also, their management is delicate, especially during the early stages of treatment. Thus, new tools to set an efficient modulation of immune response are required. The local expression of interleukin (IL) 10 protein in transplanted livers mediated by hydrodynamic gene transfer could improve the organ acceptance by the host because it presents the natural ability to modulate the immune response at different levels. In the organ transplantation scenario, IL10 has already demonstrated positive effects on graft tolerance. Hydrodynamic gene transfer has been proven to be safe and therapeutically efficient in animal models and could be easily moved to the clinic. In the present work, we evaluated efficacy of human IL10 gene transfer in human liver segments and the tissue natural barriers for gene entry into the cell, employing gold nanoparticles. In conclusion, the present work shows for the first time that hydrodynamic IL10 gene transfer to human liver segments ex vivo efficiently delivers a human gene into the cells. Indexes of tissue protein expression achieved could mediate local pharmacological effects with interest in controlling the immune response triggered after liver transplantation. On the other hand, the ultrastructural study suggests that the solubilized plasmid could access the hepatocyte in a passive manner mediated by the hydric flow and that an active mechanism of transportation could facilitate its entry into the nucleus. Liver Transplantation 23:50-62 2017 AASLD. © 2016 by the American Association for the Study of Liver Diseases.

Towards HIV-1 remission: potential roles for broadly neutralizing antibodies.

PubMed

Halper-Stromberg, Ariel; Nussenzweig, Michel C

2016-02-01

Current antiretroviral drug therapies do not cure HIV-1 because they do not eliminate a pool of long-lived cells harboring immunologically silent but replication-competent proviruses - termed the latent reservoir. Eliminating this reservoir and stimulating the immune response to control infection in the absence of therapy remain important but unsolved goals of HIV-1 cure research. Recently discovered broadly neutralizing antibodies (bNAbs) exhibit remarkable breadth and potency in their ability to neutralize HIV-1 in vitro, and recent studies have demonstrated new therapeutic applications for passively administered bNAbs in vivo. This Review discusses the roles bNAbs might play in HIV-1 treatment regimens, including prevention, therapy, and cure.

The digestive tract of Drosophila melanogaster.

PubMed

Lemaitre, Bruno; Miguel-Aliaga, Irene

2013-01-01

The digestive tract plays a central role in the digestion and absorption of nutrients. Far from being a passive tube, it provides the first line of defense against pathogens and maintains energy homeostasis by exchanging neuronal and endocrine signals with other organs. Historically neglected, the gut of the fruit fly Drosophila melanogaster has recently come to the forefront of Drosophila research. Areas as diverse as stem cell biology, neurobiology, metabolism, and immunity are benefitting from the ability to study the genetics of development, growth regulation, and physiology in the same organ. In this review, we summarize our knowledge of the Drosophila digestive tract, with an emphasis on the adult midgut and its functional underpinnings.

Breastfeeding provides passive and likely long-lasting active immunity.

PubMed

Hanson, L A

1998-12-01

The reader of this review will learn about the mechanisms through which breastfeeding protects against infections during and most likely after lactation, as well as possibly against certain immunologic diseases, including allergy. I have followed the literature in the area closely for the last 30 to 40 years and have made repeated literature searches through MEDLINE, most recently in 1998. Textbooks and peer-reviewed journals have been sought for, as well as books representing meeting reports in English, French, German, and Spanish. Human milk protects against infections in the breastfed offspring mainly via the secretory IgA antibodies, but also most likely via several other factors like the bactericidal lactoferrin. It is striking that the defense factors of human milk function without causing inflammation, some components are even directly anti-inflammatory. Protection against infections has been well evidenced during lactation against, e.g., acute and prolonged diarrhea, respiratory tract infections, otitis media, urinary tract infection, neonatal septicemia, and necrotizing enterocolitis. There is also interesting evidence for an enhanced protection remaining for years after lactation against diarrhea, respiratory tract infections, otitis media, Haemophilus influenzae type b infections, and wheezing illness. In several instances the protection seems to improve with the duration of breastfeeding. Some, but not all studies have shown better vaccine responses among breastfed than non-breastfed infants. A few factors in milk like anti-antibodies (anti-idiotypic antibodies) and T and B lymphocytes have in some experimental models been able to transfer priming of the breastfed offspring. This together with transfer of numerous cytokines and growth factors via milk may add to an active stimulation of the infant's immune system. Consequently, the infant might respond better to both infections and vaccines. Such an enhanced function could also explain why breastfeeding may protect against immunologic diseases like coeliac disease and possibly allergy. Suggestions of protection against autoimmune diseases and tumors have also been published, but need confirmation. Breastfeeding may, in addition to the well-known passive protection against infections during lactation, have a unique capacity to stimulate the immune system of the offspring possibly with several long-term positive effects.

Immunoglobulins in the eggs of the nurse shark, Ginglymostoma cirratum.

PubMed

Haines, Ashley N; Flajnik, Martin F; Rumfelt, Lynn L; Wourms, John P

2005-01-01

Elasmobranchs, which include the sharks, skates, and rays, emerged over 450 million years ago and are the oldest vertebrates to possess an adaptive immune system. They have evolved diverse reproductive modes, with a variety of physiological adaptations that enhance reproductive success. The nurse shark, Ginglymostoma cirratum, is an aplacental, viviparous elasmobranch in which the egg and its associated vitelline vasculature are the primary route for maternal-embryonic interactions. During gestation, nurse shark embryos hatch from their eggcases and develop free in the uterus, which is flushed regularly with seawater. Similar to higher vertebrates, embryonic and neonatal nurse sharks possess an immune system that is not fully competent. In birds and bony fishes, maternal immunoglobulins (Ig) stored in the egg during oogenesis confer protective immunity to embryos during gestation. However, early research suggested that such transfer of passive immunity does not occur in sharks. To better understand how elasmobranch embryos are protected from waterborne pathogens during this potentially vulnerable time, we have re-examined the existence of Igs in elasmobranch eggs. Using monoclonal antibodies, we establish the presence of two classes of Igs in nurse shark eggs: 7S IgM and IgNAR. The potential transfer of immunoglobulins from elasmobranch eggs is discussed.

The immunological response of the rat to infection with Taenia taeniaeformis. V. Sequence of appearance of protective immunoglobulins and the mechanism of action of 7Sgamma2a antibodies.

PubMed Central

Musoke, A J; Williams, J F

1975-01-01

Passive transfer of immunity to Taenia taeniaeformis was achieved with serum taken 14, 21, 49 and 63 days after infection. The protective capacity of serum collected at 14 and 21 days resided in the 7Sgamma2 immunoglobulins and appeared to be partics the infection progressed the range of chromatographic fractions showing protective capacity was extended to all those containing 7Sgamma2 and 7Sgamma1 immunoglobulins. Fractions enriched for gammaM did not confer protection. Immune serum containing 7Sgamma2a antibodies was able to kill developing parasites after they had left the intestine, and the hepatic postoncospheral forms retained their susceptibility to antibody over the first 5 days of growth. After that time they rapidly became insusceptible to antibody both in vivo and in vitro. Susceptibility to antibody-mediated attack was complement dependent. This appears to be the first time that complement has been demonstrated to play a role in immunity to a helminth infection in vivo. This finding is discussed in relation to the phenomenon of cestode parasite survival in immune animals. Images FIG. 1 PMID:1201860

Passive immunity to feline leukemia: evaluation of immunity from dams naturally infected and experimentally vaccinated.

PubMed Central

Hoover, E A; Schaller, J P; Mathes, L E; Olsen, R G

1977-01-01

Antibodies against feline leukemia virus (FeLV) and the feline oncornavirus-associated cell membrane antigen (FOCMA) were transferred from pregnant cats to their suckling kittens. All of these kittens were protected against infection and oncogenesis by virulent FeLV when challenged at 2 weeks of age. Suckling kittens acquired 25 to 100% of maternal virus-neutralizing and FOCMA titers by 3 days of age, and titers underwent linear decay to undetectable levels by 2 to 3 months of age. FOCMA antibody in dams and kittens was identified as immunoglobulin G (IgG) by use of goat anti-human IgG serum, which cross-reacts with feline IgG in the indirect membrane immunofluorescence test for FOCMA antibody. In an attempt to induce protective maternal antibody by vaccination, 10 pregnant cats were immunized by three to five weekly intramuscular injections with purified FeLV inactivated by ultraviolet irradiation. After the course of immunization, neither virus-neutralizing nor FOCMA antibody was detectable in the dams or in 19 kittens born to these cats. When these kittens were challenged with FeLV at 2 weeks of age, 18 of 19 developed persistent viremia and FeLV-related disease. Images PMID:194840

A natural human monoclonal antibody targeting Staphylococcus Protein A protects against Staphylococcus aureus bacteremia

PubMed Central

Varshney, Avanish K.; Sunley, Kevin M.; Bowling, Rodney A.; Kwan, Tzu-Yu; Mays, Heather R.; Rambhadran, Anu; Zhang, Yanfeng; Martin, Rebecca L.; Cavalier, Michael C.; Simard, John

2018-01-01

Staphylococcus aureus can cause devastating and life-threatening infections. With the increase in multidrug resistant strains, novel therapies are needed. Limited success with active and passive immunization strategies have been attributed to S. aureus immune evasion. Here, we report on a monoclonal antibody, 514G3, that circumvents a key S. aureus evasion mechanism by targeting the cell wall moiety Protein A (SpA). SpA tightly binds most subclasses of immunoglobulins via their Fc region, neutralizing effector function. The organism can thus shield itself with a protective coat of serum antibodies and render humoral immunity ineffective. The present antibody reactivity was derived from an individual with natural anti-SpA antibody titers. The monoclonal antibody is of an IgG3 subclass, which differs critically from other immunoglobulin subclasses since its Fc is not bound by SpA. Moreover, it targets a unique epitope on SpA that allows it to bind in the presence of serum antibodies. Consequently, the antibody opsonizes S. aureus and maintains effector function to enable natural immune mediated clearance. The data presented here provide evidence that 514G3 antibody is able to successfully rescue mice from S. aureus mediated bacteremia. PMID:29364906

Systemic Immunization with Papillomavirus L1 Protein Completely Prevents the Development of Viral Mucosal Papillomas

NASA Astrophysics Data System (ADS)

Suzich, Joann A.; Ghim, Shin-Je; Palmer-Hill, Frances J.; White, Wendy I.; Tamura, James K.; Bell, Judith A.; Newsome, Joseph A.; Bennett Jenson, A.; Schlegel, Richard

1995-12-01

Infection of mucosal epithelium by papillomaviruses is responsible for the induction of genital and oral warts and plays a critical role in the development of human cervical and oropharyngeal cancer. We have employed a canine model to develop a systemic vaccine that completely protects against experimentally induced oral mucosal papillomas. The major capsid protein, L1, of canine oral papillomavirus (COPV) was expressed in Sf9 insect cells in native conformation. L1 protein, which self-assembled into virus-like particles, was purified on CsCl gradients and injected intradermally into the foot pad of beagles. Vaccinated animals developed circulating antibodies against COPV and became completely resistant to experimental challenge with COPV. Successful immunization was strictly dependent upon native L1 protein conformation and L1 type. Partial protection was achieved with as little as 0.125 ng of L1 protein, and adjuvants appeared useful for prolonging the host immune response. Serum immunoglobulins passively transferred from COPV L1-immunized beagles to naive beagles conferred protection from experimental infection with COPV. Our results indicate the feasibility of developing a human vaccine to prevent mucosal papillomas, which can progress to malignancy.

Stress Proteins and Initiation of Immune Response: Chaperokine activity of Hsp72

PubMed Central

Asea, Alexzander

2006-01-01

From its original description as solely an intracellular molecular chaperone, heat shock proteins have now been shown to function as initiators of the host's immune response. Although the exact mechanism by which intracellular heat shock proteins leave cells is still incompletely understood, recent work from several labs suggest that heat shock proteins are released by both passive (necrotic) and active (physiological) mechanisms. Binding to specific surface receptors is a prerequisite for the initiation of an immune response. To date, several cell surface proteins have been described as the receptor for seventy kilo-Dalton heat shock protein (Hsp70) including Toll-like receptors 2 and 4 with their cofactor CD14, the scavenger receptor CD36, the low-density lipoprotein receptor-related protein CD91, the C-type lectin receptor LOX-1, and another member of the scavenger super-family SR-A plus the co-stimulatory molecule, CD40. Binding of Hsp70 to these surface receptors specifically activates intracellular signaling cascades, which in turn exert immunoregulatory effector functions; a process known as the chaperokine activity of Hsp70. This review will highlight recent advances in understanding the mechanism by which Hsp70 initiates the host's immune response. PMID:16385842

Stress proteins and initiation of immune response: chaperokine activity of hsp72.

PubMed

Asea, Alexzander

2005-01-01

From its original description as solely an intracellular molecular chaperone, heat shock proteins have now been shown to function as initiators of the host's immune response. Although the exact mechanism by which intracellular heat shock proteins leave cells is still incompletely understood, recent work from several labs suggest that heat shock proteins are released by both passive (necrotic) and active (physiological) mechanisms. Binding to specific surface receptors is a prerequisite for the initiation of an immune response. To date, several cell surface proteins have been described as the receptor for seventy kilo-Dalton heat shock protein (Hsp70) including Toll-like receptors 2 and 4 with their cofactor CD14, the scavenger receptor CD36, the low-density lipoprotein receptor-related protein CD91, the C-type lectin receptor LOX-1, and another member of the scavenger super-family SR-A plus the co-stimulatory molecule, CD40. Binding of Hsp70 to these surface receptors specifically activates intracellular signaling cascades, which in turn exert immunoregulatory effector functions; a process known as the chaperokine activity of Hsp70. This review will highlight recent advances in understanding the mechanism by which Hsp70 initiates the host's immune response.

Concerted Activity of IgG1 Antibodies and IL-4/IL-25-Dependent Effector Cells Trap Helminth Larvae in the Tissues following Vaccination with Defined Secreted Antigens, Providing Sterile Immunity to Challenge Infection

PubMed Central

Hewitson, James P.; Filbey, Kara J.; Esser-von Bieren, Julia; Camberis, Mali; Schwartz, Christian; Murray, Janice; Reynolds, Lisa A.; Blair, Natalie; Robertson, Elaine; Harcus, Yvonne; Boon, Louis; Huang, Stanley Ching-Cheng; Yang, Lihua; Tu, Yizheng; Miller, Mark J.; Voehringer, David; Le Gros, Graham; Harris, Nicola; Maizels, Rick M.

2015-01-01

Over 25% of the world's population are infected with helminth parasites, the majority of which colonise the gastrointestinal tract. However, no vaccine is yet available for human use, and mechanisms of protective immunity remain unclear. In the mouse model of Heligmosomoides polygyrus infection, vaccination with excretory-secretory (HES) antigens from adult parasites elicits sterilising immunity. Notably, three purified HES antigens (VAL-1, -2 and -3) are sufficient for effective vaccination. Protection is fully dependent upon specific IgG1 antibodies, but passive transfer confers only partial immunity to infection, indicating that cellular components are also required. Moreover, immune mice show greater cellular infiltration associated with trapping of larvae in the gut wall prior to their maturation. Intra-vital imaging of infected intestinal tissue revealed a four-fold increase in extravasation by LysM+GFP+ myeloid cells in vaccinated mice, and the massing of these cells around immature larvae. Mice deficient in FcRγ chain or C3 complement component remain fully immune, suggesting that in the presence of antibodies that directly neutralise parasite molecules, the myeloid compartment may attack larvae more quickly and effectively. Immunity to challenge infection was compromised in IL-4Rα- and IL-25-deficient mice, despite levels of specific antibody comparable to immune wild-type controls, while deficiencies in basophils, eosinophils or mast cells or CCR2-dependent inflammatory monocytes did not diminish immunity. Finally, we identify a suite of previously uncharacterised heat-labile vaccine antigens with homologs in human and veterinary parasites that together promote full immunity. Taken together, these data indicate that vaccine-induced immunity to intestinal helminths involves IgG1 antibodies directed against secreted proteins acting in concert with IL-25-dependent Type 2 myeloid effector populations. PMID:25816012

Homeostatic and pathogenic extramedullary hematopoiesis

PubMed Central

Kim, Chang H

2010-01-01

Extramedullary hematopoiesis (EH) is defined as hematopoiesis occurring in organs outside of the bone marrow; it occurs in diverse conditions, including fetal development, normal immune responses, and pathological circumstances. During fetal development, before formation of mature marrow, EH occurs in the yolk sac, fetal liver, and spleen. EH also occurs during active immune responses to pathogens. Most frequently, this response occurs in the spleen and liver for the production of antigen-presenting cells and phagocytes. EH also occurs when the marrow becomes inhabitable for stem and progenitor cells in certain pathological conditions, including myelofibrosis, where marrow cells are replaced with collagenous connective tissue fibers. Thus, EH occurs either actively or passively in response to diverse changes in the hematopoietic environment. This article reviews the key features and regulators of the major types of EH. PMID:22282679

Detecting contaminant-induced apoptosis and necrosis in lake trout thymocytes via flow cytometry.

USGS Publications Warehouse

Sweet, Leonard I.; Passino-Reader, Dora R.; Meier, Peter G.; Omann, Geneva M.; Stolen, J.S.; Fletcher, T.C.; Rowley, A.F.; Zelikoff, J.T.; Kaattari, S.L.; Smith, S.A.

1997-01-01

This chapter details the cytofluorometric techniques employed to assess levels of active (apoptosis) and passive (necrotic) cell death in untreated and contaminant-treated fish thymocytes. The thymus is believed to be a central component of hematopoiesis and immune function in teleosts (Abelli et al., 1996). Hence, chemically-elicited adverse effects to the thymus may result in immunomodulation and organ dysfunction. However, it is not well documented that environmental contaminants induce apoptosis, or programmed cell death. There is some evidence suggesting that low level exposure to waterborne contaminants can specifically induce cell death in the olfactory epithelium of rainbow trout (Julliard et al., 1996). Presently, only limited information is available in the literature regarding apoptotic death in piscine immune cells (Alford et al., 1994; Greenlee et al., 1991).

EVOLUTION OF SARCOMA 37 IN CF1 RATS. BIOLOGICAL ASPECTS OF THE SPONTANEOUS CURE OF TUMORS STUDIED AFTER IRRADIATION AND ADMINISTRATION OF IMMUNE SERUM. Evolucao do sarcoma 37 em muganhos CF1. Aspectos biologicos da cura espontianea do tumor estudados apos irradiacao e administracao de soro imune (in Portuguese)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Clode, William H.

Transplants of sarcoma 37 were studied in regard to spontaneous regression of the tumor after irradiation and after the administration of immune serum. The following results were obtained: 1. Of 809 animals, 99% developed the tumor after transplantation; 2. The number of cells transplanted did not influence the growth rate, the percentage of spontaneous regressions, or the life spans of the animals; 3. Reimplantation of the tumor into mice which had previously rejected the tumor resulted in very few successful transplants; 4. The resistance of these mice to further attempts at implantation could not be altered by previous irradiation; 5.more » Animals transplanted for the first time suffer a faster evolution of the tumor, shortened life span, and a diminution of spontaneous regressions if they have been irradiated prior to transplantation (400r whole body); and, 6. Resistance to tumor growth could not be transferred passively in serum of mice which had rejected the tumor.« less

High-performance multi-channel fiber-based absolute distance measuring interferometer system

NASA Astrophysics Data System (ADS)

Deck, Leslie L.

2009-08-01

I describe the principle of operation and performance of a fiber-based absolute distance measuring interferometer system with 60 independent simultaneous channels. The system was designed for demanding applications requiring passive, electrically immune sensors with an extremely long MTTF. In addition to providing better than 0.3nm measurement repeatability at 5KHz for all channels, the system demonstrated absolute distance uncertainty of less than 5nm over a 500 micron measurement range.

Sequential immunization with V3 peptides from primary human immunodeficiency virus type 1 produces cross-neutralizing antibodies against primary isolates with a matching narrow-neutralization sequence motif.

PubMed

Eda, Yasuyuki; Takizawa, Mari; Murakami, Toshio; Maeda, Hiroaki; Kimachi, Kazuhiko; Yonemura, Hiroshi; Koyanagi, Satoshi; Shiosaki, Kouichi; Higuchi, Hirofumi; Makizumi, Keiichi; Nakashima, Toshihiro; Osatomi, Kiyoshi; Tokiyoshi, Sachio; Matsushita, Shuzo; Yamamoto, Naoki; Honda, Mitsuo

2006-06-01

An antibody response capable of neutralizing not only homologous but also heterologous forms of the CXCR4-tropic human immunodeficiency virus type 1 (HIV-1) MNp and CCR5-tropic primary isolate HIV-1 JR-CSF was achieved through sequential immunization with a combination of synthetic peptides representing HIV-1 Env V3 sequences from field and laboratory HIV-1 clade B isolates. In contrast, repeated immunization with a single V3 peptide generated antibodies that neutralized only type-specific laboratory-adapted homologous viruses. To determine whether the cross-neutralization response could be attributed to a cross-reactive antibody in the immunized animals, we isolated a monoclonal antibody, C25, which neutralized the heterologous primary viruses of HIV-1 clade B. Furthermore, we generated a humanized monoclonal antibody, KD-247, by transferring the genes of the complementary determining region of C25 into genes of the human V region of the antibody. KD-247 bound with high affinity to the "PGR" motif within the HIV-1 Env V3 tip region, and, among the established reference antibodies, it most effectively neutralized primary HIV-1 field isolates possessing the matching neutralization sequence motif, suggesting its promise for clinical applications involving passive immunizations. These results demonstrate that sequential immunization with B-cell epitope peptides may contribute to a humoral immune-based HIV vaccine strategy. Indeed, they help lay the groundwork for the development of HIV-1 vaccine strategies that use sequential immunization with biologically relevant peptides to overcome difficulties associated with otherwise poorly immunogenic epitopes.

Sequential Immunization with V3 Peptides from Primary Human Immunodeficiency Virus Type 1 Produces Cross-Neutralizing Antibodies against Primary Isolates with a Matching Narrow-Neutralization Sequence Motif

PubMed Central

Eda, Yasuyuki; Takizawa, Mari; Murakami, Toshio; Maeda, Hiroaki; Kimachi, Kazuhiko; Yonemura, Hiroshi; Koyanagi, Satoshi; Shiosaki, Kouichi; Higuchi, Hirofumi; Makizumi, Keiichi; Nakashima, Toshihiro; Osatomi, Kiyoshi; Tokiyoshi, Sachio; Matsushita, Shuzo; Yamamoto, Naoki; Honda, Mitsuo

2006-01-01

An antibody response capable of neutralizing not only homologous but also heterologous forms of the CXCR4-tropic human immunodeficiency virus type 1 (HIV-1) MNp and CCR5-tropic primary isolate HIV-1 JR-CSF was achieved through sequential immunization with a combination of synthetic peptides representing HIV-1 Env V3 sequences from field and laboratory HIV-1 clade B isolates. In contrast, repeated immunization with a single V3 peptide generated antibodies that neutralized only type-specific laboratory-adapted homologous viruses. To determine whether the cross-neutralization response could be attributed to a cross-reactive antibody in the immunized animals, we isolated a monoclonal antibody, C25, which neutralized the heterologous primary viruses of HIV-1 clade B. Furthermore, we generated a humanized monoclonal antibody, KD-247, by transferring the genes of the complementary determining region of C25 into genes of the human V region of the antibody. KD-247 bound with high affinity to the “PGR” motif within the HIV-1 Env V3 tip region, and, among the established reference antibodies, it most effectively neutralized primary HIV-1 field isolates possessing the matching neutralization sequence motif, suggesting its promise for clinical applications involving passive immunizations. These results demonstrate that sequential immunization with B-cell epitope peptides may contribute to a humoral immune-based HIV vaccine strategy. Indeed, they help lay the groundwork for the development of HIV-1 vaccine strategies that use sequential immunization with biologically relevant peptides to overcome difficulties associated with otherwise poorly immunogenic epitopes. PMID:16699036

Indications for laser therapy in diverse models of periodontitis

NASA Astrophysics Data System (ADS)

Kunin, Anatoly A.; Erina, Stanislava V.; Sokolova, Irina A.; Pankova, Svetlana N.; Ippolitov, Yu. A.; Lepechina, L. I.; Malinovskaya, L. A.; Chitrina, L. L.

1996-11-01

Parodontal diseases have an immunological pathogenic mechanism leading to various manifestations and can not be referred to as a common inflammation. The home and foreign research points at active and immunological reaction with the following distraction surrounding tissues of the tooth. Histochemical and biochemical examinations show metabolic disturbances of parodontal tissues. A total sample size of 604 people suffering from average height of chronic generalized parodontitis was examined in the survey. Immunological and histochemical tests were taken before and after a course of laser therapy with the use of helium-neon laser 'YAGODA', an inhibitory and stimulating dosage irradiations and anti-inflammatory dosage irradiations with infrared laser 'UZOR'. We selected a group of patients with the decreased local immunological status on the ground of immunological tests. Histochemical tests shaped the next group with the passive and active forms of parodontitis pathology. The tests data resulted in a method of laser therapy. The investigations confirm that the chronic generalized parodontitis has a shift in tissue immunity of the oral cavity and cell-bound metabolic disturbance of gum epithelium. It is expedient to use the anti-inflammatory dosage irradiations with infrared laser 'UZOR' to correct immunity, and in case of and active process to realize the DNA and RNA synthesis by means of increasing the irradiation with the apparatus 'YAGODA'. The irradiation decreases in case of a passive process.

A Cross-Reactive Monoclonal Antibody to Nematode Haemoglobin Enhances Protective Immune Responses to Nippostrongylus brasiliensis

PubMed Central

Nieuwenhuizen, Natalie E.; Meter, Jeanne M.; Horsnell, William G.; Hoving, J. Claire; Fick, Lizette; Sharp, Michael F.; Darby, Matthew G.; Parihar, Suraj P.; Brombacher, Frank; Lopata, Andreas L.

2013-01-01

Background Nematode secreted haemoglobins have unusually high affinity for oxygen and possess nitric oxide deoxygenase, and catalase activity thought to be important in protection against host immune responses to infection. In this study, we generated a monoclonal antibody (48Eg) against haemoglobin of the nematode Anisakis pegreffii, and aimed to characterize cross-reactivity of 4E8g against haemoglobins of different nematodes and its potential to mediate protective immunity against a murine hookworm infection. Methodology/Principal Findings Immunoprecipitation was used to isolate the 4E8g-binding antigen in Anisakis and Ascaris extracts, which were identified as haemoglobins by peptide mass fingerprinting and MS/MS. Immunological cross-reactivity was also demonstrated with haemoglobin of the rodent hookworm N. brasiliensis. Immunogenicity of nematode haemoglobin in mice and humans was tested by immunoblotting. Anisakis haemoglobin was recognized by IgG and IgE antibodies of Anisakis-infected mice, while Ascaris haemoglobin was recognized by IgG but not IgE antibodies in mouse and human sera. Sequencing of Anisakis haemoglobin revealed high similarity to haemoglobin of a related marine nematode, Psuedoterranova decipiens, which lacks the four –HKEE repeats of Ascaris haemoglobin important in octamer assembly. The localization of haemoglobin in the different parasites was examined by immunohistochemistry and associated with the excretory-secretary ducts in Anisakis, Ascaris and N. brasiliensis. Anisakis haemoglobin was strongly expressed in the L3 stage, unlike Ascaris haemoglobin, which is reportedly mainly expressed in adult worms. Passive immunization of mice with 4E8g prior to infection with N. brasiliensis enhanced protective Th2 immunity and led to a significant decrease in worm burdens. Conclusion The monoclonal antibody 4E8g targets haemoglobin in broadly equivalent anatomical locations in parasitic nematodes and enhances host immunity to a hookworm infection. PMID:24009787

Immunotherapy for lung cancer: advances and prospects.

PubMed

Yang, Li; Wang, Liping; Zhang, Yi

2016-01-01

Lung cancer is the most commonly diagnosed cancer as well as the leading cause of cancer-related deaths worldwide. To date, surgery is the first choice treatment, but most clinically diagnosed cases are inoperable. While chemotherapy and/or radiotherapy are the next considered options for such cases, these treatment modalities have adverse effects and are sometimes lethal to patients. Thus, new effective strategies with minimal side effects are urgently needed. Cancer immunotherapy provides either active or passive immunity to target tumors. Multiple immunotherapy agents have been proposed and tested for potential therapeutic benefit against lung cancer, and some pose fewer side effects as compared to conventional chemotherapy and radiotherapy. In this article, we discuss studies focusing on interactions between lung cancer and the immune system, and we place an emphasis on outcome evidence in order to create a knowledge base well-grounded in clinical reality. Overall, this review highlights the need for new lung cancer treatment options, with much ground to be paved for future advances in the field. We believe that immunotherapy agents alone or with other forms of treatment can be recognized as next modality of lung cancer treatment.

Tick-Borne Encephalitis Virus Vaccine-Induced Human Antibodies Mediate Negligible Enhancement of Zika Virus Infection InVitro and in a Mouse Model.

PubMed

Duehr, James; Lee, Silviana; Singh, Gursewak; Foster, Gregory A; Krysztof, David; Stramer, Susan L; Bermúdez González, Maria C; Menichetti, Eva; Geretschläger, Robert; Gabriel, Christian; Simon, Viviana; Lim, Jean K; Krammer, Florian

2018-01-01

Recent reports in the scientific literature have suggested that anti-dengue virus (DENV) and anti-West Nile virus (WNV) immunity exacerbates Zika virus (ZIKV) pathogenesis in vitro and in vivo in mouse models. Large populations of immune individuals exist for a related flavivirus (tick-borne encephalitis virus [TBEV]), due to large-scale vaccination campaigns and endemic circulation throughout most of northern Europe and the southern Russian Federation. As a result, the question of whether anti-TBEV immunity can affect Zika virus pathogenesis is a pertinent one. For this study, we obtained 50 serum samples from individuals vaccinated with the TBEV vaccine FSME-IMMUN (Central European/Neudörfl strain) and evaluated their enhancement capacity in vitro using K562 human myeloid cells expressing CD32 and in vivo using a mouse model of ZIKV pathogenesis. Among the 50 TBEV vaccinee samples evaluated, 29 had detectable reactivity against ZIKV envelope (E) protein by enzyme-linked immunosorbent assay (ELISA), and 36 showed enhancement of ZIKV infection in vitro . A pool of the most highly reacting and enhanced samples resulted in no significant change in the morbidity/mortality of ZIKV disease in immunocompromised Stat2 -/- mice. Our results suggest that humoral immunity against TBEV is unlikely to enhance Zika virus pathogenesis in humans. No clinical reports indicating that TBEV vaccinees experiencing enhanced ZIKV disease have been published so far, and though the epidemiological data are sparse, our findings suggest that there is little reason for concern. This study also displays a clear relationship between the phylogenetic distance between two flaviviruses and their capacity for pathogenic enhancement. IMPORTANCE The relationship between serial infections of two different serotypes of dengue virus and more severe disease courses is well-documented in the literature, driven by so-called antibody-dependent enhancement (ADE). Recently, studies have shown the possibility of ADE in cells exposed to anti-DENV human plasma and then infected with ZIKV and also in mouse models of ZIKV pathogenesis after passive transfer of anti-DENV human plasma. In this study, we evaluated the extent to which this phenomenon occurs using sera from individuals immunized against tick-borne encephalitis virus (TBEV). This is highly relevant, since large proportions of the European population are vaccinated against TBEV or otherwise seropositive.

Is there a maternally induced immunological imprinting phase à la Konrad Lorenz?

PubMed

Lemke, H; Lange, H

1999-10-01

In mammals, IgG antibodies are transferred from mothers to the offspring. Since these maternal antibodies result mainly from thymus-dependent immune responses which have undergone immune maturation through somatic hypermutations, they represent the highest quality of the collective maternal immunological experience. Maternal antibodies not only confer passive immunity as long as the newborn's immune system has not fully developed, but also exert an active stimulation as indicated by their regulatory influence on isotype expression, long-term idiotypic alterations, determination of the adult B and T cell repertoire, induction of antigen reactive IgM as well as an affinity enhancement of a proportion of early primary antibodies. The fact that several of these features can only be induced during limited sensitive periods shortly after birth is reminiscent of the behavioural imprinting as defined by Konrad Lorenz. We therefore propose that during early ontogeny there is an immunological imprinting phase with characteristics analogous to behavioural imprinting: (i) the internal imprinting effect is induced by external signals, (ii) in contrast to normal learning, immunological imprinting is also only possible during certain development phases and (iii) it is characterised by an (almost) irreversible result. Hence, if particular immunological experiences are only possible during such sensitive phases, maternal immunoglobulins and consequently the mother's immunological experience is of prime importance for the start of the ontogenetic development of the immune system.

What the shark immune system can and cannot provide for the expanding design landscape of immunotherapy.

PubMed

Criscitiello, Michael F

2014-07-01

Sharks have successfully lived in marine ecosystems, often atop food chains as apex predators, for nearly one and a half billion years. Throughout this period they have benefitted from an immune system with the same fundamental components found in terrestrial vertebrates like man. Additionally, sharks have some rather extraordinary immune mechanisms which mammals lack. In this review the author briefly orients the reader to sharks, their adaptive immunity, and their important phylogenetic position in comparative immunology. The author also differentiates some of the myths from facts concerning these animals, their cartilage, and cancer. From thereon, the author explores some of the more remarkable capabilities and products of shark lymphocytes. Sharks have an isotype of light chain-less antibodies that are useful tools in molecular biology and are moving towards translational use in the clinic. These special antibodies are just one of the several tricks of shark lymphocyte antigen receptor systems. While shark cartilage has not helped oncology patients, shark immunoglobulins and T cell receptors do offer exciting novel possibilities for immunotherapeutics. Much of the clinical immunology developmental pipeline has turned from traditional vaccines to passively delivered monoclonal antibody-based drugs for targeted depletion, activation, blocking and immunomodulation. The immunogenetic tools of shark lymphocytes, battle-tested since the dawn of our adaptive immune system, are well poised to expand the design landscape for the next generation of immunotherapy products.

Advances in systemic delivery of anti-cancer agents for the treatment of metastatic cancer.

PubMed

Grundy, Megan; Coussios, Constantin; Carlisle, Robert

2016-07-01

The successful treatment of metastatic cancer is refractory to strategies employed to treat confined, primary lesions, such as surgical resection and radiation therapy, and thus must be addressed by systemic delivery of anti-cancer agents. Conventional systemically administered chemotherapeutics are often ineffective and come with severe dose-limiting toxicities. This review focuses on the recent developments in systemic therapy for metastatic cancer. Firstly, the strategies employed to improve the efficacy of conventional chemotherapeutics by 'passively' and 'actively' targeting them to tumors are discussed. Secondly, recent advances in the use of biologics to better target cancer and to instigate anti-tumor immunity are reviewed. Under the label of 'biologics', antibody-therapies, T cell engaging therapies, oncolytic virotherapies and cell-based therapies are examined and evaluated. Improving specificity of action, and engaging the immune system appear to be key goals in the development of novel or reformulated anti-cancer agents for the treatment of metastatic cancer. One of the largest areas of opportunity in this field will be the identification of robust predictive biomarkers for use in conjunction with these agents. Treatment regimens that combine an agent to elicit an immune response (such as an oncolytic virus), and an agent to potentiate/mediate that immune response (such as immune checkpoint inhibitors) are predicted to be more effective than treatment with either agent alone.

Progress and novel strategies in vaccine development and treatment of anthrax.

PubMed

Chitlaru, Theodor; Altboum, Zeev; Reuveny, Shaul; Shafferman, Avigdor

2011-01-01

The lethal anthrax disease is caused by spores of the gram-positive Bacillus anthracis, a member of the cereus group of bacilli. Although the disease is very rare in the Western world, development of anthrax countermeasures gains increasing attention due to the potential use of B. anthracis spores as a bio-terror weapon. Protective antigen (PA), the non-toxic subunit of the bacterial secreted exotoxin, fulfills the role of recognizing a specific receptor and mediating the entry of the toxin into the host target cells. PA elicits a protective immune response and represents the basis for all current anthrax vaccines. Anti-PA neutralizing antibodies are useful correlates for protection and for vaccine efficacy evaluation. Post exposure anti-toxemic and anti-bacteremic prophylactic treatment of anthrax requires prolonged antibiotic administration. Shorter efficient postexposure treatments may require active or passive immunization, in addition to antibiotics. Although anthrax is acknowledged as a toxinogenic disease, additional factors, other than the bacterial toxin, may be involved in the virulence of B. anthracis and may be needed for the long-lasting protection conferred by PA immunization. The search for such novel factors is the focus of several high throughput genomic and proteomic studies that are already leading to identification of novel targets for therapeutics, for vaccine candidates, as well as biomarkers for detection and diagnosis. © 2010 John Wiley & Sons A/S.

Production of specific IgY antibody to the recombinant FanC protein produced in Escherichia coli.

PubMed

Nasiri, Khadijeh; Zibaee, Saeed; Nassiri, Mohammadreza; Tahmoorespur, Mojtaba; Haghparast, Alireza

2016-08-01

Enterotoxigenic Escherichia coli (ETEC) strains are one of the primary causes of diarrhea in newborn calves and in humans, pigs, and sheep. IgY technology has been identified as a promising alternative to generating a mass amount of specific antibody for use in immunotherapy and immunodiagnostics. The purpose of this study was to produce specific antibody by egg yolk antibody (IgY) to recombinant FanC protein from ETEC. FanC (K99) gene was amplified from ETEC by specific primers and polymerase chain reaction. The gene was cloned and subcloned into pTZ57R/T and pET32a (+) vectors, respectively. Recombinant vector was transferred into E. coli BL21 CodonPlus (DE3). Protein expression was investigated by 1 mM IPTG induction. Hens were immunized by the purified recombinant FanC protein. The activity and specificity of the IgY antibody were detected by dot-blotting, Western blotting, and indirect ELISA. We obtained FanC specific IgYs by immunizing the hens with the recombinant FanC protein. The anti-FanC IgY showed binding specifically to the FanC protein of ETEC. The results emphasize that specific IgY against the recombinant FanC protein could be recommended as a candidate for passive immunization against ETEC infection in animals and humans.

Production of specific IgY antibody to the recombinant FanC protein produced in Escherichia coli

PubMed Central

Nasiri, Khadijeh; Zibaee, Saeed; Nassiri, Mohammadreza; Tahmoorespur, Mojtaba; Haghparast, Alireza

2016-01-01

Objective(s): Enterotoxigenic Escherichia coli (ETEC) strains are one of the primary causes of diarrhea in newborn calves and in humans, pigs, and sheep. IgY technology has been identified as a promising alternative to generating a mass amount of specific antibody for use in immunotherapy and immunodiagnostics. The purpose of this study was to produce specific antibody by egg yolk antibody (IgY) to recombinant FanC protein from ETEC. Materials and Methods: FanC (K99) gene was amplified from ETEC by specific primers and polymerase chain reaction. The gene was cloned and subcloned into pTZ57R/T and pET32a (+) vectors, respectively. Recombinant vector was transferred into E. coli BL21 CodonPlus (DE3). Protein expression was investigated by 1 mM IPTG induction. Hens were immunized by the purified recombinant FanC protein. The activity and specificity of the IgY antibody were detected by dot-blotting, Western blotting, and indirect ELISA. Results: We obtained FanC specific IgYs by immunizing the hens with the recombinant FanC protein. The anti-FanC IgY showed binding specifically to the FanC protein of ETEC. Conclusion: The results emphasize that specific IgY against the recombinant FanC protein could be recommended as a candidate for passive immunization against ETEC infection in animals and humans. PMID:27746871

Immune response in pemphigus and beyond: progresses and emerging concepts.

PubMed

Di Zenzo, Giovanni; Amber, Kyle T; Sayar, Beyza S; Müller, Eliane J; Borradori, Luca

2016-01-01

Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are two severe autoimmune bullous diseases of the mucosae and/or skin associated with autoantibodies directed against desmoglein (Dsg) 3 and/or Dsg1. These two desmosomal cadherins, typifying stratified epithelia, are components of cell adhesion complexes called desmosomes and represent extra-desmosomal adhesion receptors. We herein review the advances in our understanding of the immune response underlying pemphigus, including human leucocyte antigen (HLA) class II-associated genetic susceptibility, characteristics of pathogenic anti-Dsg antibodies, antigenic mapping studies as well as findings about Dsg-specific B and T cells. The pathogenicity of anti-Dsg autoantibodies has been convincingly demonstrated. Disease activity and clinical phenotype correlate with anti-Dsg antibody titers and profile while passive transfer of anti-Dsg IgG from pemphigus patients' results in pemphigus-like lesions in neonatal and adult mice. Finally, adoptive transfer of splenocytes from Dsg3-knockout mice immunized with murine Dsg3 into immunodeficient mice phenotypically recapitulates PV. Although the exact pathogenic mechanisms leading to blister formation have not been fully elucidated, intracellular signaling following antibody binding has been found to be necessary for inducing cell-cell dissociation, at least for PV. These new insights not only highlight the key role of Dsgs in maintenance of tissue homeostasis but are expected to progressively change pemphigus management, paving the way for novel targeted immunologic and pharmacologic therapies.

Latently and uninfected healthcare workers exposed to TB make protective antibodies against Mycobacterium tuberculosis.

PubMed

Li, Hao; Wang, Xing-Xing; Wang, Bin; Fu, Lei; Liu, Guan; Lu, Yu; Cao, Min; Huang, Hairong; Javid, Babak

2017-05-09

The role of Igs in natural protection against infection by Mycobacterium tuberculosis (Mtb), the causative agent of TB, is controversial. Although passive immunization with mAbs generated against mycobacterial antigens has shown protective efficacy in murine models of infection, studies in B cell-depleted animals only showed modest phenotypes. We do not know if humans make protective antibody responses. Here, we investigated whether healthcare workers in a Beijing TB hospital-who, although exposed to suprainfectious doses of pathogenic Mtb, remain healthy-make antibody responses that are effective in protecting against infection by Mtb. We tested antibodies isolated from 48 healthcare workers and compared these with 12 patients with active TB. We found that antibodies from 7 of 48 healthcare workers but none from active TB patients showed moderate protection against Mtb in an aerosol mouse challenge model. Intriguingly, three of seven healthcare workers who made protective antibody responses had no evidence of prior TB infection by IFN-γ release assay. There was also good correlation between protection observed in vivo and neutralization of Mtb in an in vitro human whole-blood assay. Antibodies mediating protection were directed against the surface of Mtb and depended on both immune complexes and CD4+ T cells for efficacy. Our results indicate that certain individuals make protective antibodies against Mtb and challenge paradigms about the nature of an effective immune response to TB.

The DUV Stability of Superlattice-Doped CMOS Detector Arrays

NASA Technical Reports Server (NTRS)

Hoenk, M. E.; Carver, A.; Jones, T.; Dickie, M.; Cheng, P.; Greer, H. F.; Nikzad, S.; Sgro, J.

2013-01-01

In this paper, we present experimental results and band structure calculations that illuminate the unique properties of superlattice-doped detectors. Numerical band structure calculations are presented to analyze the dependencies of surface passivation on dopant profiles and interface trap densities (Figure 3). Experiments and calculations show that quantum-engineered surfaces, grown at JPL by low temperature molecular beam epitaxy, achieve a qualitative as well as quantitative uniqueness in their near-immunity to high densities of surface and interface traps.

Staphylococcal and Streptococcal Superantigen Exotoxins

PubMed Central

Spaulding, Adam R.; Salgado-Pabón, Wilmara; Kohler, Petra L.; Horswill, Alexander R.; Leung, Donald Y. M.

2013-01-01

SUMMARY This review begins with a discussion of the large family of Staphylococcus aureus and beta-hemolytic streptococcal pyrogenic toxin T lymphocyte superantigens from structural and immunobiological perspectives. With this as background, the review then discusses the major known and possible human disease associations with superantigens, including associations with toxic shock syndromes, atopic dermatitis, pneumonia, infective endocarditis, and autoimmune sequelae to streptococcal illnesses. Finally, the review addresses current and possible novel strategies to prevent superantigen production and passive and active immunization strategies. PMID:23824366

Immunization in pregnancy.

PubMed

Gruslin, Andrée; Steben, Marc; Halperin, Scott; Money, Deborah M; Yudin, Mark H

2009-11-01

To review the evidence and provide recommendations on immunization in pregnancy. Outcomes evaluated include effectiveness of immunization, risks and benefits for mother and fetus. The Medline and Cochrane databases were searched for articles published up to June 2008 on the topic of immunization in pregnancy. The evidence obtained was reviewed and evaluated by the Infectious Diseases Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC) under the leadership of the principal authors, and recommendations were made according to guidelines developed by the Canadian Task Force on Preventive Health Care. Implementation of the recommendations in this guideline should result in more appropriate immunization of pregnant and breastfeeding women, decreased risk of contraindicated immunization, and better disease prevention. The quality of evidence reported in this document has been assessed using the evaluation of evidence criteria in the Report of the Canadian Task Force on Preventive Health Care (Table 1). (1) All women of childbearing age should be evaluated for the possibility of pregnancy before immunization. (III-A). (2) Health care providers should obtain a relevant immunization history from all women accessing prenatal care. (III-A). (3) In general, live and/or live-attenuated virus vaccines should not be administered during pregnancy, as there is a, largely theoretical, risk to the fetus. (II-3B). (4) Women who have inadvertently received immunization with live or live-attenuated vaccines during pregnancy should not be counselled to terminate the pregnancy because of a teratogenic risk. (II-2A). (5) Non-pregnant women immunized with a live or live-attenuated vaccine should be counselled to delay pregnancy for at least four weeks. (III-B). (6) Inactivated viral vaccines, bacterial vaccines, and toxoids can be used safely in pregnancy. (II-1A). (7) Women who are breastfeeding can still be immunized (passive-active immunization, live or killed vaccines). (II-1A) (8) Pregnant women should be offered the influenza vaccine (including H1N1 vaccine, when it is available) when they are pregnant during the influenza season. (II-1A). (9) Pregnant women with suspected or documented H1N1 infection should be treated with oseltamivir (Tamiflu, 75 mg twice daily for 5 days) within 48 hours of onset of symptoms. (III-B).

Regulation of immunotherapeutic products for cancer and FDA’s role in product development and clinical evaluation

PubMed Central

2013-01-01

Immunotherapeutics include drugs and biologics that render therapeutic benefit by harnessing the power of the immune system. The promise of immune-mediated therapies is target specificity with a consequent reduction in off-target side effects. Recent scientific advances have led to clinical trials of both active and passive immunotherapeutic products that have the potential to convert life-ending diseases into chronic but manageable conditions. Clinical trials investigating immunotherapeutics are ongoing with some trials at advanced stages of development. However, as with many products involving novel mechanisms of action, major regulatory and scientific issues arising with clinical use of immunotherapeutic products remain to be addressed. In this review, we address issues related to different immunotherapeutics and provide recommendations for the characterization and evaluation of these products during various stages of product and clinical development. PMID:24764535

[Natural infection by hemoparasites in calves submitted to chemoprophylaxis at 30 days of age].

PubMed

da Silva, Rosângela A; Corrêa, Fabíola do N; Botteon, Rita de Cássia C M; Botteon, Paulo de Tarso L

2007-01-01

The tick-borne disease (TBD) brings great damages to cattle breeding. The most important etiologic agents are Babesia bigemina, B. bovis and Anaplasma marginale, being the tick Boophilus microplus the main vector. This work reports the occurrence of natural infection by hemoparasites of TBD in 36 calves with high ticks natural infestation submitted to chemoprophylaxis with 30 days year-old. The blood smears from animals of different ages were analized and were found B. bigemina (33.3%), B. bovis (11.1%) and A. marginale (13.9%). Six animals had clinical symptoms (16.7%) and one dead (2.8%). The number of clinical cases ocurred in consequence of an association of factors as high infestation of ticks and low passive immunity in period that calves had not developed enough active immunity.

Antibody-Based Agents in the Management of Antibiotic-Resistant Staphylococcus aureus Diseases

PubMed Central

Speziale, Pietro; Rindi, Simonetta

2018-01-01

Staphylococcus aureus is a human pathogen that can cause a wide spectrum of diseases, including sepsis, pneumonia, arthritis, and endocarditis. Ineffective treatment of a number of staphylococcal infections with antibiotics is due to the development and spread of antibiotic-resistant strains following decades of antibiotic usage. This has generated renewed interest within the scientific community in alternative therapeutic agents, such as anti-S. aureus antibodies. Although the role of antibodies in the management of S. aureus diseases is controversial, the success of this pathogen in neutralizing humoral immunity clearly indicates that antibodies offer the host extensive protection. In this review, we report an update on efforts to develop antibody-based agents, particularly monoclonal antibodies, and their therapeutic potential in the passive immunization approach to the treatment and prevention of S. aureus infections. PMID:29533985

Epilepsy and innate immune system: A possible immunogenic predisposition and related therapeutic implications.

PubMed

Matin, Nassim; Tabatabaie, Omidreza; Falsaperla, Raffaele; Lubrano, Riccardo; Pavone, Piero; Mahmood, Fahad; Gullotta, Melissa; Serra, Agostino; Di Mauro, Paola; Cocuzza, Salvatore; Vitaliti, Giovanna

2015-01-01

Recent experimental studies and pathological analyses of patient brain tissue samples with refractory epilepsy suggest that inflammatory processes and neuroinflammation plays a key-role in the etiopathology of epilepsy and convulsive disorders. These inflammatory processes lead to the secretion of pro-inflammatory cytokines responsible for blood-brain-barrier disruption and involvement of resident immune cells in the inflammation pathway, occurring within the Central Nervous System (CNS). These elements are produced through activation of Toll-Like Receptors (TLRs) by exogenous and endogenous ligands thereby increasing expression of cytokines and co-stimulatory molecules through the activation of TLRs 2, 3, 4, and 9 as reported in murine studies.It has been demonstrated that IL-1β intracellular signaling and cascade is able to alter the neuronal excitability without cell loss. The activation of the IL-1β/ IL-1β R axis is strictly linked to the secretion of the intracellular protein MyD88, which interacts with other cell surface receptors, such as TLR4 during pathogenic recognition. Furthermore, TLR-signaling pathways are able to recognize molecules released from damaged tissues, such as damage-associated molecular patterns/proteins (DAMPs). Among these molecules, High-mobility group box-1 (HMGB1) is a component of chromatin that is passively released from necrotic cells and actively released by cells that are subject to profound stress. Moreover, recent studies have described models of epilepsy induced by the administration of bicuculline and kainic acid that highlight the nature of HMGB1-TLR4 interactions, their intracellular signaling pathway as well as their role in ictiogenesis and epileptic recurrence.The aim of our review is to focus on different branches of innate immunity and their role in epilepsy, emphasizing the role of immune related molecules in epileptogenesis and highlighting the research implications for novel therapeutic strategies.

Production and characterization of egg yolk antibody (IgY) against recombinant VP8-S2 antigen.

PubMed

Nasiri, K; Nassiri, M R; Tahmoorespur, M; Haghparast, A; Zibaee, S

2016-01-01

Bovine Rotavirus and Bovine Coronavirus are the most important causes of diarrhea in newborn calves and in some other species such as pigs and sheep. VP8 subunit of rotavirus is the major determinant of the viral infectivity and neutralization. Spike glycoprotein of coronavirus is responsible for induction of neutralizing antibody response. Studies showed that immunoglobulin of egg yolk (IgY) from immunized hens has been identified to be a convenient source for specific antibodies for using in immunotherapy and immunodiagnostic to limit the infections. In this study, chimeric VP8-S2 gene was designed using by computational techniques. The chimeric VP8-S2 gene was cloned and sub-cloned into pGH and pET32a (+) vectors. Then, recombinant pET32a-VP8-S2 vector was transferred into E. coli BL21 CodonPlus (DE3). The expressed protein was purified by Ni-NTA chromatography column. Hens were immunized with the purified VP8-S2 protein three times. IgY was purified from egg yolks using polyethylene glycol precipitation method. Activity and specificity of anti-VP8-S2 IgY were detected by dot-blotting, Western-blotting and indirect ELISA. We obtained anti-VP8-S2 IgY by immunizing hens with the recombinant VP8-S2 protein. The anti-VP8-S2 IgY was showed to bind specifically to the chimeric VP8-S2 protein by dot-blotting, Western-blotting analyses and indirect ELISA. The result of this study indicated that such construction can be useful to investigate as candidates for development of detection methods for simultaneous diagnosis of both infections. Specific IgY against the recombinant VP8-S2 could be recommended as a candidate for passive immunization against bovine rotavirus and bovine coronavirus.

Use of electronic immunization registry in the surveillance of adverse events following immunization

PubMed Central

Sato, Ana Paula Sayuri; Ferreira, Vinícius Leati de Rossi; Tauil, Márcia de Cantuária; Rodrigues, Laura Cunha; Barros, Mariana Bernardes; Martineli, Edmar; Costa, Ângela Aparecida; Inenami, Marta; Waldman, Eliseu Alves

2018-01-01

ABSTRACT OBJECTIVE To describe adverse events following vaccination (AEFV) of children under two years old and analyze trend of this events from 2000 to 2013, in the city of Araraquara (SP), Brazil. METHODS This is a descriptive study conducted with data of the passive surveillance system of AEFV that is available in the electronic immunization registry (EIR) of the computerized medical record of the municipal health service (Juarez System). The study variables were: age, gender, vaccine, dose, clinical manifestations and hospitalization. We estimated rates using AEFV as numerator and administered doses of vaccines as denominator. The surveillance sensitivity was estimated by applying the method proposed by the Centers for Disease Control and Prevention. We used Prais-Winsten regression with a significance level of 5.0%. RESULTS The average annual rate of AEFV was 11.3/10,000 administered doses, however without a trend in the study period (p=0.491). Most cases occurred after the first dose (41.7%) and among children under one year of age (72.6%). Vaccines with pertussis component, yellow fever and measles-mumps-rubella were the most reactogenic. We highlighted the rates of hypotonic-hyporesponsive episodes and convulsion that were 4.1/10,000 and 1.5/10,000 doses of vaccines with pertussis component, respectively, most frequently in the first dose; 60,0% of cases presented symptoms in the first 24 hours after vaccination, however, 18.6% showed after 96 hours. The sensitivity of surveillance was 71.9% and 78.9% for hypotonic-hyporesponsive episodes and convulsion, respectively. CONCLUSIONS The EIR-based AEFV surveillance system proved to be useful and highly sensitive to describe the safety profile of vaccines in a medium-sized city. It was also shown that the significant increase of the vaccines included in the basic vaccination schedule in childhood in the last decade did not alter the high safety standard of the National Immunization Program. PMID:29412373

Use of electronic immunization registry in the surveillance of adverse events following immunization.

PubMed

Sato, Ana Paula Sayuri; Ferreira, Vinícius Leati de Rossi; Tauil, Márcia de Cantuária; Rodrigues, Laura Cunha; Barros, Mariana Bernardes; Martineli, Edmar; Costa, Ângela Aparecida; Inenami, Marta; Waldman, Eliseu Alves

2018-02-05

To describe adverse events following vaccination (AEFV) of children under two years old and analyze trend of this events from 2000 to 2013, in the city of Araraquara (SP), Brazil. This is a descriptive study conducted with data of the passive surveillance system of AEFV that is available in the electronic immunization registry (EIR) of the computerized medical record of the municipal health service (Juarez System). The study variables were: age, gender, vaccine, dose, clinical manifestations and hospitalization. We estimated rates using AEFV as numerator and administered doses of vaccines as denominator. The surveillance sensitivity was estimated by applying the method proposed by the Centers for Disease Control and Prevention. We used Prais-Winsten regression with a significance level of 5.0%. The average annual rate of AEFV was 11.3/10,000 administered doses, however without a trend in the study period (p=0.491). Most cases occurred after the first dose (41.7%) and among children under one year of age (72.6%). Vaccines with pertussis component, yellow fever and measles-mumps-rubella were the most reactogenic. We highlighted the rates of hypotonic-hyporesponsive episodes and convulsion that were 4.1/10,000 and 1.5/10,000 doses of vaccines with pertussis component, respectively, most frequently in the first dose; 60,0% of cases presented symptoms in the first 24 hours after vaccination, however, 18.6% showed after 96 hours. The sensitivity of surveillance was 71.9% and 78.9% for hypotonic-hyporesponsive episodes and convulsion, respectively. The EIR-based AEFV surveillance system proved to be useful and highly sensitive to describe the safety profile of vaccines in a medium-sized city. It was also shown that the significant increase of the vaccines included in the basic vaccination schedule in childhood in the last decade did not alter the high safety standard of the National Immunization Program.

HMGB1, an innate alarmin, plays a critical role in chronic inflammation of adipose tissue in obesity.

PubMed

Zhang, Jing; Zhang, Lei; Zhang, Shu; Yu, Qilin; Xiong, Fei; Huang, Kun; Wang, Cong-Yi; Yang, Ping

2017-10-15

Obesity has emerged as an imminent global public health concern over the past several decades. It has now become evident that obesity is characterized by the persistent and low-grade inflammation in the adipose tissue, and serves as an independent risk factor for many metabolic disorders such as diabetes and cardiovascular disease. Particularly, adipocytes originated from obese mice and humans likely predominate necrosis upon stressful insults, leading to passive release of cellular contents including the high mobility group box 1 (HMGB1) into the extracellular milieu. Extracellular HMGB1 acts as an innate alarmin to stimulate the activation of resident immune cells in the adipose tissue. Upon activation, those resident immune cells actively secrete additional HMGB1, which in turn activates/recruits additional immune cells, and induces adipocyte death. This review summarizes those novel discoveries in terms of HMGB1 in the initiation and maintenance of chronic inflammatory state in adipose tissue in obesity, and discusses its potential application in clinical settings. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Dengue vaccine development: strategies and challenges.

PubMed

Ramakrishnan, Lakshmy; Pillai, Madhavan Radhakrishna; Nair, Radhakrishnan R

2015-03-01

Infection with dengue virus may result in dengue fever or a more severe outcome, such as dengue hemorrhagic syndrome/shock. Dengue virus infection poses a threat to endemic regions for four reasons: the presence of four serotypes, each with the ability to cause a similar disease outcome, including fatality; difficulties related to vector control; the lack of specific treatment; and the nonavailability of a suitable vaccine. Vaccine development is considered challenging due to the severity of the disease observed in individuals who have acquired dengue-specific immunity, either passively or actively. Therefore, the presence of vaccine-induced immunity against a particular serotype may prime an individual to severe disease on exposure to dengue virus. Vaccine development strategies include live attenuated vaccines, chimeric, DNA-based, subunit, and inactivated vaccines. Each of the candidates is in various stages of preclinical and clinical development. Issues pertaining to selection pressures, viral interaction, and safety still need to be evaluated in order to induce a complete protective immune response against all four serotypes. This review highlights the various strategies that have been employed in vaccine development, and identifies the obstacles to producing a safe and effective vaccine.

Low-level light treatment ameliorates immune thrombocytopenia

PubMed Central

Yang, Jingke; Zhang, Qi; Li, Peiyu; Dong, Tingting; Wu, Mei X.

2016-01-01

Immune thrombocytopenia (ITP) is an immune-mediated acquired bleeding disorder characterized by abnormally low platelet counts. We reported here the ability of low-level light treatment (LLLT) to alleviate ITP in mice. The treatment is based on noninvasive whole body illumination 30 min a day for a few consecutive days by near infrared light (830 nm) transmitted by an array of light-emitting diodes (LEDs). LLLT significantly lifted the nadir of platelet counts and restored tail bleeding time when applied to two passive ITP models induced by anti-CD41 antibody. The anti-platelet antibody hindered megakaryocyte differentiation from the progenitors, impaired proplatelet and platelet formation, and induced apoptosis of platelets. These adverse effects of anti-CD41 antibody were all mitigated by LLLT to varying degrees, owing to its ability to enhance mitochondrial biogenesis and activity in megakaryocytes and preserve mitochondrial functions in platelets in the presence of the antibody. The observations argue not only for contribution of mitochondrial stress to the pathology of ITP, but also clinical potentials of LLLT as a safe, simple, and cost-effective modality of ITP. PMID:27901126

Low-level light treatment ameliorates immune thrombocytopenia

NASA Astrophysics Data System (ADS)

Yang, Jingke; Zhang, Qi; Wu, Mei X.

2017-02-01

Immune thrombocytopenia (ITP) is an immune-mediated acquired bleeding disorder characterized by abnormally low platelet counts. We reported here the ability of low-level light treatment (LLLT) to alleviate ITP in mice. The treatment is based on noninvasive whole body illumination 30 min a day for a few consecutive days by near infrared light (830 nm) transmitted by an array of light-emitting diodes (LEDs). LLLT significantly lifted the nadir of platelet counts and restored tail bleeding time when applied to two passive ITP models induced by anti-CD41 antibody. The anti-platelet antibody hindered megakaryocyte differentiation from the progenitors, impaired proplatelet and platelet formation, and induced apoptosis of platelets. These adverse effects of anti-CD41 antibody were all mitigated by LLLT to varying degrees, owing to its ability to enhance mitochondrial biogenesis and activity in megakaryocytes and preserve mitochondrial functions in platelets in the presence of the antibody. The observations argue not only for contribution of mitochondrial stress to the pathology of ITP, but also clinical potentials of LLLT as a safe, simple, and cost-effective modality of ITP.

Inactivated coxsackievirus A10 experimental vaccines protect mice against lethal viral challenge.

PubMed

Shen, Chaoyun; Liu, Qingwei; Zhou, Yu; Ku, Zhiqiang; Wang, Lili; Lan, Ke; Ye, Xiaohua; Huang, Zhong

2016-09-22

Coxsackievirus A10 (CVA10) has become one of the major causative agents of hand, foot and mouth disease (HFMD). It is now recognized that CVA10 should be targeted for vaccine development. We report here that β-propiolactone inactivated whole-virus based CVA10 vaccines can elicit protective immunity in mice. We prepared two inactivated CVA10 experimental vaccines derived from the prototype strain CVA10/Kowalik and from a clinical isolate CVA10/S0148b, respectively. Immunization with the experimental vaccines elicited CVA10-specific serum antibodies in mice. The antisera from vaccinated mice could potently neutralize in vitro infection with either homologous or heterologous CVA10 strains. Importantly, passive transfer of the anti-CVA10 sera protected recipient mice against CVA10/Kowalik or CVA10/S0148b infections. Moreover, active immunization with the inactivated vaccines also conferred protection against homologous and heterologous infections in mice. Collectively, our results demonstrate the proof-of-concept for inactivated whole-virus based CVA10 vaccines. Copyright © 2016 Elsevier Ltd. All rights reserved.

Report of the 2014 Cent Gardes HIV Vaccine Conference-Part 2: Cell-mediated immunity, mucosal protection, and clinical trials: Fondation Mérieux Conference Center, Veyrier du Lac, France, 5-7 October, 2014.

PubMed

Girard, Marc P; Picot, Valentina; Longuet, Christophe; Nabel, Gary J

2015-08-07

The 2014 Cent Gardes Conference took place on October 5-7, 2014, at the Fondation Mérieux Conference Center, on the shores of the Annecy Lake and aimed to review the progress and promise of HIV vaccines. The elicitation of broadly neutralizing antibodies (bNAbs), their use in passive immunization, as well as their genetic delivery (vector immunoprophylaxis) by a recombinant Adenovirus-associated virus (AAV) vector were reviewed in a preceding article [1]. Approaches to the elicitation of long-lasting T cell or mucosal immunity were also discussed and are now reviewed here. The possibility of eliciting mucosal IgAs was discussed, since it was demonstrated that transcytosis-blocking IgAs can protect monkeys against repeated vaginal challenge with a pathogenic chimeric simian and human immunodeficiency virus (SHIV). The possibility of purging the HIV reservoirs from HIV-infected persons and developing a cure of the disease was also discussed. Copyright © 2015. Published by Elsevier Ltd.. All rights reserved.

The Contribution of Systemic and Pulmonary Immune Effectors to Vaccine-Induced Protection from H5N1 Influenza Virus Infection

PubMed Central

Lau, Yuk-Fai; Wright, Amber R.

2012-01-01

Live attenuated influenza vaccines (LAIVs) are effective in providing protection against influenza challenge in animal models and in preventing disease in humans. We previously showed that LAIVs elicit a range of immune effectors and that successful induction of pulmonary cellular and humoral immunity in mice requires pulmonary replication of the vaccine virus. An upper respiratory tract immunization (URTI) model was developed in mice to mimic the human situation, in which the vaccine virus does not replicate in the lower respiratory tract, allowing us to assess the protective efficacy of an H5N1 LAIV against highly pathogenic H5N1 virus challenge in the absence of significant pulmonary immunity. Our results show that, after one dose of an H5N1 LAIV, pulmonary influenza-specific lymphocytes are the main contributors to clearance of challenge virus from the lungs and that contributions of influenza-specific enzyme-linked immunosorbent assay (ELISA) antibodies in serum and splenic CD8+ T cells were negligible. Complete protection from H5N1 challenge was achieved after two doses of H5N1 LAIV and was associated with maturation of the antibody response. Although passive transfer of sera from mice that received two doses of vaccine prevented lethality in naive recipients following challenge, the mice showed significant weight loss, with high pulmonary titers of the H5N1 virus. These data highlight the importance of mucosal immunity in mediating optimal protection against H5N1 infection. Understanding the requirements for effective induction and establishment of these protective immune effectors in the respiratory tract paves the way for a more rational and effective vaccine approach in the future. PMID:22379093

Immunization with Recombinantly Expressed LRP4 Induces Experimental Autoimmune Myasthenia Gravis in C57BL/6 Mice.

PubMed

Ulusoy, Canan; Çavuş, Filiz; Yılmaz, Vuslat; Tüzün, Erdem

2017-07-01

Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction (NMJ), characterized with muscle weakness. While MG develops due to acetylcholine receptor (AChR) antibodies in most patients, antibodies to muscle-specific receptor tyrosine kinase (MuSK) or low-density lipoprotein receptor-related protein 4 (LRP4) may also be identified. Experimental autoimmune myasthenia gravis (EAMG) has been previously induced by both LRP4 immunization and passive transfer of LRP4 antibodies. Our aim was to confirm previous results and to test the pathogenic effects of LRP4 immunization in a commonly used mouse strain C57BL/6 (B6) using a recombinantly expressed human LRP4 protein. B6 mice were immunized with human LRP4 in CFA, Torpedo Californica AChR in CFA or only CFA. Clinical and pathogenic aspects of EAMG were compared among groups. LRP4- and AChR-immunized mice showed comparable EAMG clinical severity. LRP4-immunized mice displayed serum antibodies to LRP4 and NMJ IgG and complement factor C3 deposits. IgG2 was the dominant anti-LRP4 isotype. Cultured lymph node cells of LRP4- and AChR-immunized mice gave identical pro-inflammatory cytokine (IL-6, IFN-γ and IL-17) responses to LRP4 and AChR stimulation, respectively. Our results confirm the EAMG-inducing action of LRP4 immunization and identify B6 as a LRP4-EAMG-susceptible mouse strain. Demonstration of complement fixing anti-LRP4 antibodies in sera and complement/IgG deposits at the NMJ of LRP4-immunized mice indicates complement activation as a putative pathogenic mechanism. We have thus developed a practical LRP4-induced EAMG model using a non-conformational protein and a widely available mouse strain for future investigation of LRP4-related MG.

The effect of immunization on measles incidence in the Democratic Republic of Congo: Results from a model of surveillance data.

PubMed

Doshi, Reena H; Shidi, Calixte; Mulumba, Audry; Eckhoff, Philip; Nguyen, Catherine; Hoff, Nicole A; Gerber, Sue; Okitolonda, Emile; Ilunga, Benoit Kebela; Rimoin, Anne W

2015-11-27

Measles continues to be a leading cause of vaccine-preventable disease mortality among children under five despite a safe and efficacious vaccine being readily available. While global vaccination coverage has improved tremendously, measles outbreaks persist throughout sub-Saharan Africa. Since 2010, the Democratic Republic of Congo (DRC) has seen a resurgence of measles outbreaks affecting all 11 provinces. These outbreaks are mainly attributed to gaps in routine immunization (RI) coverage compounded with missed supplementary immunization activities (SIAs). We utilized national passive surveillance data from DRC's Integrated Disease Surveillance and Response (IDSR) system to estimate the effect of immunization on measles incidence in DRC. We investigated the decline in measles incidence post-immunization with one dose of measles containing vaccine (MCV1) with and without the addition of supplementary immunization activities (SIAs) and outbreak response immunization (ORI) campaigns. Measles case counts by health zone were obtained from the IDSR system between January 1, 2010 and December 31, 2013. The impact of measles immunization was modeled using a random effects multi-level model for count data with RI coverage levels and mass campaign activities from one year prior. The presence of an SIA (aIRR [95% CI] 0.86 [0.60-1.25]) and ORI (0.28 [0.20-0.39]) in the year prior were both associated with a decrease in measles incidence. When interaction terms were included, our results suggested that the high levels of MCV1 reported in the year prior and the presence of either mass campaign was associated with a decrease in measles incidence. Our results highlight the importance of a two-dose measles vaccine schedule and the need for a strong routine immunization program coupled with frequent SIAs. Repeated occurrences of large-scale outbreaks in DRC suggest that vaccination coverage rates are grossly overestimated and signify the importance of the evaluation and modification of measles prevention and control strategies. Copyright © 2015 Elsevier Ltd. All rights reserved.

[Evaluation of modern epizootic activity of natural tularemia foci in Voronezh region using immune-serological and molecular-genetic study of main carriers of the disease].

PubMed

Meshcheriakova, I S; Trankvilevskiĭ, D V; Kvasov, D A; Mikhaĭlova, T V; Kormilitsina, M I; Demidova, T N; Stepkin, Iu I; Zhukov, V I

2015-01-01

Improvement of monitoring and prognosis of epidemic manifestations of natural foci of tularemia on the territory of Voronezh region using immune-serological and molecular-genetic study of main carriers of the disease. 539 small mammals captured during summer period of 2011 in 4 districts of North-Eastern part of Voronezh region were studied. Animal organs were studied by serologic (search for Francisella tularensis antigens) and molecular-biologic (detection of F. tularensis DNA) methods. Tularemia antigen was detected using passive hemagglutination reaction (PHAR) with erythrocytic tularemia immunoglobulin diagnosticum. Real-time polymerase chain reaction (RT-PCR) was applied for detection of tularemia causative agent DNA. Complex study revealed epizootic activity of natural foci of tularemia in the examined territory. F. tularensis antigen and/or DNA were detected in 82 objects (15.2%). Use of RT-PCR allowed to additionally detect samples with relatively low content of F. tularensis DNA substrate, when antigen was not detected in samples. High sensitivity and specificity of the RT-PCR was ensured by inclusion of specific probes (tu14-PR2 and ISFTu2P). The results obtained give evidence on functioning and epizootic activity of natural foci of tularemia in Voronezh region that requires constant monitoring of the territory and prophylaxis measures, first of all vaccination of risk groups by live tularemia vaccine.

Developing novel immunogens for a safe and effective Alzheimer's disease vaccine.

PubMed

Lemere, Cynthia A

2009-01-01

Alzheimer's disease (AD) is the most prevalent form of neurodegeneration; however, therapies to prevent or treat AD are inadequate. Amyloid-beta (Abeta) protein accrues in cortical senile plaques, one of the key neuropathological hallmarks of AD, and is elevated in brains of early onset AD patients in a small number of families that bear certain genetic mutations, further implicating its role in this devastating neurological disease. In addition, soluble Abeta oligomers have been shown to be detrimental to neuronal function. Therapeutic strategies aimed at lowering cerebral Abeta levels are currently under development. One strategy is to immunize AD patients with Abeta peptides so that they will generate antibodies that bind to Abeta protein and enhance its clearance. As of 1999, Abeta immunotherapy, either through active immunization with Abeta peptides or through passive transfer of Abeta-specific antibodies, has been shown to reduce cerebral Abeta levels and improve cognitive deficits in AD mouse models and lower plaque load in nonhuman primates. However, a Phase II clinical trial of active immunization using full-length human Abeta1-42 peptide and a strong Th1-biased adjuvant, QS-21, ended prematurely in 2002 because of the onset of meningoencephalitis in approximately 6% of the AD patients enrolled in the study. It is possible that T cell recognition of the human full-length Abeta peptide as a self-protein may have induced an adverse autoimmune response in these patients. Although only approximately 20% of immunized patients generated anti-Abeta titers, responders showed some general slowing of cognitive decline. Focal cortical regions devoid of Abeta plaques were observed in brain tissues of several immunized patients who have since come to autopsy. In order to avoid a deleterious immune response, passive Abeta immunotherapy is under investigation by administering monthly intravenous injections of humanized Abeta monoclonal antibodies to AD patients. However, a safe and effective active Abeta vaccine would be more cost-effective and more readily available to a larger AD population. We have developed several novel short Abeta immunogens that target the Abeta N-terminus containing a strong B cell epitope while avoiding the Abeta mid-region and C-terminus containing T cell epitopes. These immunogens include dendrimeric Abeta1-15 (16 copies of Abeta1-15 on a lysine antigen tree), 2xAbeta1-15 (a tandem repeat of two lysine-linked Abeta1-15 peptides), and 2xAbeta1-15 with the addition of a three amino acid RGD motif (R-2xAbeta1-15). Intranasal immunization with our short Abeta fragment immunogens and a mucosal adjuvant, mutant Escherichia coli heat-labile enterotoxin LT(R192G), resulted in reduced cerebral Abeta levels, plaque deposition, and gliosis, as well as increased plasma Abeta levels and improved cognition in a transgenic mouse model of AD. Preclinical trials in nonhuman primates, and human clinical trials using similar Abeta immunogens, are now underway. Abeta immunotherapy looks promising but must be made safer and more effective at generating antibody titers in the elderly. It is hoped that these novel immunogens will enhance Abeta antibody generation across a broad population and avoid the adverse events seen in the earlier clinical trial.

Protein transduction domain of transactivating transcriptional activator fused to outer membrane protein K of Vibrio parahaemolyticus to vaccinate marbled eels (Anguilla marmorata) confers protection against mortality caused by V. parahaemolyticus.

PubMed

Wang, Hang; Yang, Wei; Shen, Guoying; Zhang, Jianting; Lv, Wei; Ji, Binfeng; Meng, Chun

2015-07-01

Although immersion and oral vaccination are the most practical methods for fish farmers, their applications are very limited due to low immune stimulation effect. We used the protein transduction domain (PTD) of transactivating transcriptional factor (TAT) derived from HIV TAT protein to increase the delivery efficiency of aquatic protein vaccines. Vibrio parahaemolyticus outer membrane protein K (ompK), a reported vaccine candidate for the prevention of V. parahaemolyticus infection, was fused with TAT-PTD expressed in Escherichia coli. We found that PTD-ompK fusion protein effectively penetrated into marbled eel bodies. Analysis of ompK antibody titres demonstrated that immersion vaccination with PTD-ompK was superior to ompK alone and induced robust immune stimulation in marbled eels. Both active and passive protection analyses against immersive challenge with V. parahaemolyticus strains demonstrated that marbled eels immunized with PTD-ompK survived significantly longer than those immunized with ompK alone. Our results indicated that TAT-PTD could be served as is an efficient delivery system for aquatic immersion vaccinations against various infectious diseases commonly seen in aquatic farm industry. © 2015 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

A novel recombinant anti-epidermal growth factor receptor peptide vaccine capable of active immunization and reduction of tumor volume in a mouse model.

PubMed

Asadi-Ghalehni, Majid; Rasaee, Mohamad Javad; RajabiBazl, Masoumeh; Khosravani, Masood; Motaghinejad, Majid; Javanmardi, Masoud; Khalili, Saeed; Modjtahedi, Helmout; Sadroddiny, Esmaeil

2017-12-01

Over-expression of epidermal growth factor receptor (EGFR) has been reported in a number of human malignancies. Strong expression of this receptor has been associated with poor survival in many such patients. Active immunizations that elicit antibodies of the desired type could be an appealing alternative to conventional passive immunization. In this regard, a novel recombinant peptide vaccine capable of prophylactic and therapeutic effects was constructed. A novel fusion recombinant peptide base vaccine consisting of L2 domain of murine extra-cellular domain-EGFR and EGFR mimotope (EM-L2) was constructed and its prophylactic and therapeutic effects in a Lewis lung carcinoma mouse (C57/BL6) model evaluated. Constructed recombinant peptide vaccine is capable of reacting with anti-EGFR antibodies. Immunization of mice with EM-L2 peptide resulted in antibody production against EM-L2. The constructed recombinant peptide vaccine reduced tumor growth and increased the survival rate. Designing effective peptide vaccines could be an encouraging strategy in contemporary cancer immunotherapy. Investigating the efficacy of such cancer immunotherapy approaches may open exciting possibilities concerning hyperimmunization, leading to more promising effects on tumor regression and proliferation. © 2017 The Societies and John Wiley & Sons Australia, Ltd.

Immunization with a novel chimeric peptide representing B and T cell epitopes from HER2 extracellular domain (HER2 ECD) for breast cancer.

PubMed

Mahdavi, Manijeh; Keyhanfar, Mehrnaz; Jafarian, Abbas; Mohabatkar, Hassan; Rabbani, Mohammad

2014-12-01

Because of direct stimulating immune system against disease, vaccination or active immunotherapy is preferable compared to passive immunotherapy. For this purpose, a newly designed chimeric peptide containing epitopes for both B and T cells from HER2 ECD subdomain III was proposed. To evaluate the effects of the active immunization, a discontinuous B cell epitope peptide was selected based on average antigenicity by bioinformatics analysis. The selected peptide was collinearly synthesized as a chimera with a T helper epitope from the protein sequence of measles virus fusion (208-302) using the GPSL linker. Three mice were immunized with the chimeric peptide. Reactive antibodies with HER2 protein in ELISA and immunofluorescence assays with no cross-reactivity were generated. The 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay indicated that the anti-peptide sera had inhibitory effects on proliferation of SK-BR-3 cells. Hence, the newly designed, discontinuous chimeric peptide representing B and T cell epitopes from subdomain III of HER2-ECD can form the basis for future vaccines design, where these data can be applied for monoclonal antibody production targeting the distinct epitope of HER2 receptor compared to the two broadly used anti-HER2 monoclonal antibodies, Herceptin and pertuzumab.

Immunity to adult cestodes: basic knowledge and vaccination problems. A review.

PubMed

Andreassen, J

1991-04-01

Immunity in mammals to intestinal cestodes has been reviewed using the normal final host infected with the tapeworms Hymenolepis diminuta in rats and H. microstoma and H. nana in mice as a model. Primary infections up to a certain level continue to live as long the host, while most worms in infections with larger doses are destrobilated and expelled. It has been argued that concomitant immunity against a superimposed infection exists in rats and mice infected with H. diminuta and H. microstoma, respectively, and suggested that it also takes place in humans infected with Taenia spp. Immunity to secondary infections after expulsion of a primary infection occurs, but immunological memory is rather short-lived, although depression of worm growth occurs for at least two third of the rat's life. Serum antibodies have been shown to produce a direct precipitate on the surface of cestodes in vitro, but a direct effect of antibodies in vivo or the relationship with e.g. host effector cells, like mast cells and eosinophils, is unknown. It has been shown that peritoneal exudate cells from rats are able to kill H. diminuta in vitro. Very little is known about the mechanisms of tapeworms to counteract host immunological responses, but the tegumental glycoconjugates and discoidal secretory bodies are possible candidates. Passive transfer of immunity by mesenteric lymph node cells has only been successful using cells from H. nana egg-infected mice and has shown that only short-lived proliferating cells are responsible for transferring immunity. Vaccination procedures and problems are discussed with special reference to E. granulosus in dogs.

Comparison of selected canine vaccines for their ability to induce protective immunity against canine parvovirus infection.

PubMed

Larson, L J; Schultz, R D

1997-04-01

To compare the ability of 6 commercially available multicomponent canine vaccines to stimulate antibody production in pups with variable amounts of maternally derived canine parvovirus (CPV) antibody and to induce protective immunity against challenge exposure. Sixty-three 5- to 6-week-old Beagle pups with passively acquired CPV antibody titer between 1: 20 and 1:320. 9 pups were assigned to each of 6 vaccine groups and 1 control group. Eight pups in each group were inoculated with vaccine or saline solution twice, with 3 weeks between administrations. The ninth pup served as an uninoculated contact control. Serum samples were obtained weekly and tested for CPV antibody by hemagglutination-inhibition assay. All pups were challenge exposed with virulent CPV-2a and CPV-2b at 14 to 15 weeks of age. 3 of the vaccines failed to provide protective immunity against challenge exposure because all pups in these groups became infected and most died. A fourth vaccine protected against death, but not infection and disease. Two of the 6 vaccines induced an immune response that was protective against infection and disease. Substantial differences existed among commercial vaccines available in 1994 in their ability to immunize pups with maternally derived CPV antibody. These differences caused many vaccinated pups to be susceptible to CPV disease for variable periods because some vaccines failed to immunize. Importantly, all 4 of the vaccines that performed poorly have recently been replaced by more effective products so that the 6 vaccines now perform similarly.

Measles elimination and immunisation: national surveillance trends in Japan, 2008-2015.

PubMed

Inaida, S; Matsuno, S; Kobune, F

2017-08-01

Measles elimination relies on vaccination programmes. In Japan, a major outbreak started in 2007. In response, 5-year two-dose catch-up vaccination programme was initiated in April 2008 for children 13-16-years-old. In this study, we analysed the epidemic curves, incidence rates for each age group, virus genotype, vaccination coverage and ratio of measles gelatin particle agglutination (PA) antibody using surveillance data for 2008-2015. Monthly case counts markedly decreased as vaccination coverage increased. D5, which is the endemic virus type, disappeared after 2011, with the following epidemic caused by imported viruses. Most cases were confirmed to have a no-dose or single-dose vaccination status. Although the incidence rate among all age groups ⩾5-years-old decreased during the study period, for children <5-years-old, the incidence rate remained relatively high and increased in 2014. The ratio of PA antibody (⩾1:128 titres) increased for the majority of age groups, but with a decrease for specific age groups: the 0-5 months and the 2-4, 14, 19 and most of the 26-55- and the 60-year-old groups (-1 to -9%). This seems to be the result of higher vaccination coverage, which would result in decreasing natural immunity booster along with decreasing passive immunity in infants whose mothers did not have the natural immunity booster. The 20-29- and 30-39-year-old age groups had higher number of cases, suggesting that vaccination within these age groups might be important for eliminating imported viruses.

Post-exposure Treatment with Anti-rabies VHH and Vaccine Significantly Improves Protection of Mice from Lethal Rabies Infection

PubMed Central

Terryn, Sanne; Francart, Aurélie; Rommelaere, Heidi; Stortelers, Catelijne; Van Gucht, Steven

2016-01-01

Post-exposure prophylaxis (PEP) against rabies infection consists of a combination of passive immunisation with plasma-derived human or equine immune globulins and active immunisation with vaccine delivered shortly after exposure. Since anti-rabies immune globulins are expensive and scarce, there is a need for cheaper alternatives that can be produced more consistently. Previously, we generated potent virus-neutralising VHH, also called Nanobodies, against the rabies glycoprotein that are effectively preventing lethal disease in an in vivo mouse model. The VHH domain is the smallest antigen-binding functional fragment of camelid heavy chain-only antibodies that can be manufactured in microbial expression systems. In the current study we evaluated the efficacy of half-life extended anti-rabies VHH in combination with vaccine for PEP in an intranasal rabies infection model in mice. The PEP combination therapy of systemic anti-rabies VHH and intramuscular vaccine significantly delayed the onset of disease compared to treatment with anti-rabies VHH alone, prolonged median survival time (35 versus 14 days) and decreased mortality (60% versus 19% survival rate), when treated 24 hours after rabies virus challenge. Vaccine alone was unable to rescue mice from lethal disease. As reported also for immune globulins, some interference of anti-rabies VHH with the antigenicity of the vaccine was observed, but this did not impede the synergistic effect. Post exposure treatment with vaccine and human anti-rabies immune globulins was unable to protect mice from lethal challenge. Anti-rabies VHH and vaccine act synergistically to protect mice after rabies virus exposure, which further validates the possible use of anti-rabies VHH for rabies PEP. PMID:27483431

Polymeric immunoglobulin receptor in intestinal immune defense against the lumen-dwelling protozoan parasite Giardia.

PubMed

Davids, Barbara J; Palm, J E Daniel; Housley, Michael P; Smith, Jennifer R; Andersen, Yolanda S; Martin, Martin G; Hendrickson, Barbara A; Johansen, Finn-Eirik; Svärd, Staffan G; Gillin, Frances D; Eckmann, Lars

2006-11-01

The polymeric Ig receptor (pIgR) is conserved in mammals and has an avian homologue, suggesting evolutionarily important functions in vertebrates. It transports multimeric IgA and IgM across polarized epithelia and is highly expressed in the intestine, yet little direct evidence exists for its importance in defense against common enteric pathogens. In this study, we demonstrate that pIgR can play a critical role in intestinal defense against the lumen-dwelling protozoan parasite Giardia, a leading cause of diarrheal disease. The receptor was essential for the eradication of Giardia when high luminal IgA levels were required. Clearance of Giardia muris, in which IgA plays a dominant role, was severely compromised in pIgR-deficient mice despite significant fecal IgA output at 10% of normal levels. In contrast, eradication of the human strain Giardia lamblia GS/M, for which adaptive immunity is less IgA dependent in mice, was unaffected by pIgR deficiency, indicating that pIgR had no physiologic role when lower luminal IgA levels were sufficient for parasite elimination. Immune IgA was greatly increased in the serum of pIgR-deficient mice, conferred passive protection against Giardia, and recognized several conserved giardial Ags, including ornithine carbamoyltransferase, arginine deiminase, alpha-enolase, and alpha- and beta-giardins, that are also detected in human giardiasis. Corroborative observations were made in mice lacking the J chain, which is required for pIgR-dependent transepithelial IgA transport. These results, together with prior data on pIgR-mediated immune neutralization of luminal cholera toxin, suggest that pIgR is essential in intestinal defense against pathogenic microbes with high-level and persistent luminal presence.

Anti-amyloid beta to tau - based immunization: Developments in immunotherapy for Alzheimer disease.

PubMed

Lambracht-Washington, Doris; Rosenberg, Roger N

2013-08-01

Immunotherapy might provide an effective treatment for Alzheimer disease (AD). A unique feature of AD immunotherapies is that an immune response against a self antigen needs to be elicited without causing adverse autoimmune reactions. Current research is focussed on two possible targets in this regard: One is the inhibition of accumulation and deposition of Amyloid beta 1-42 (Aβ42), which is one of the major peptides found in senile plaques and the second target is hyperphosphorylated tau, which forms neurofibrillary tangles inside the nerve cell and shows association with the progression of dementia. Mouse models have shown that immunotherapy targeting Aβ42 as well as tau with the respective anti-Aβ or anti-tau antibodies can provide significant improvements in these mice. While anti-Aβ immunotherapy (active and passive immunizations) is already in several stages of clinical trials, tau based immunizations have been analyzed only in mouse models. Recently, as a significant correlation of progression of dementia and levels of phoshorylated tau was found, high interest has again focussed on further development of tau based therapies. While Aβ immunotherapy might delay the onset of AD, immunotherapy targeting tau might provide benefits in later stages of this disease. And last but not least, targeting Aβ and tau simultaneously with immunotherapy might provide additional therapeutic effects as these two pathologies are likely synergistic; an approach which has not been tested yet. In this review, we will summarize animal models used to test possible therapies for AD, some of the facts about Aβ42 and tau biology, present on overview on halted, ongoing and upcoming clinical trials together with ongoing preclinical studies targeting tau or Aβ42.

Experimental Modification of Rat Pituitary Prolactin Cell Function During and After Spaceflight

NASA Technical Reports Server (NTRS)

Hymer, W. C.; Salada, T.; Avery, L.; Grindeland, R. E.

1996-01-01

Experimental modification of rat pituitary prolactin cell function during and after spaceflight. This study was done to evaluate the effects of microgravity on prolactin (PRL) cells of the male rat pituitary gland. We used the identical passive closed-vial cell culture system that was described for the culture of growth hormone cells (W C. Hymer, R. E. Grindeland, T. Salada, P. Nye, E. Grossman, and R Lane). After an 8-day spaceflight, all flight media (containing released PRL), as well as extracts (containing intracellular PRL), contained significantly lower amounts of immunoreactive PRL than their corresponding ground control samples. On the other hand, these same samples, when assessed for their biological activities by two different in vitro lymphocyte assays, yielded disparate results that may reflect posttranslational modifications to the hormone molecule. Other data showed that: (1) the apparent molecular weights of released PRL molecules were not altered by microgravity; but (2) the region from which the PRL cells came (dorsal or ventral) made a significant difference in the amount and activity of PRL released from the flight cells. Because there is much current interest in the role that PRL may play in the regulation of the immune system and because changes in both cellular and humoral immunity accompany spaceflight, this study could help define future microgravity research in this area.

Puzzling inefficiency of H5N1 influenza vaccines in Egyptian poultry

PubMed Central

Kim, Jeong-Ki; Kayali, Ghazi; Walker, David; Forrest, Heather L.; Ellebedy, Ali H.; Griffin, Yolanda S.; Rubrum, Adam; Bahgat, Mahmoud M.; Kutkat, M. A.; Ali, M. A. A.; Aldridge, Jerry R.; Negovetich, Nicholas J.; Krauss, Scott; Webby, Richard J.; Webster, Robert G.

2010-01-01

In Egypt, efforts to control highly pathogenic H5N1 avian influenza virus in poultry and in humans have failed despite increased biosecurity, quarantine, and vaccination at poultry farms. The ongoing circulation of HP H5N1 avian influenza in Egypt has caused >100 human infections and remains an unresolved threat to veterinary and public health. Here, we describe that the failure of commercially available H5 poultry vaccines in Egypt may be caused in part by the passive transfer of maternal H5N1 antibodies to chicks, inhibiting their immune response to vaccination. We propose that the induction of a protective immune response to H5N1 is suppressed for an extended period in young chickens. This issue, among others, must be resolved and additional steps must be taken before the outbreaks in Egypt can be controlled. PMID:20534457

Passive immunization with Leptospira LPS-specific agglutinating but not non-agglutinating monoclonal antibodies protect guinea pigs from fatal pulmonary hemorrhages induced by serovar Copenhageni challenge.

PubMed

Challa, Sreerupa; Nally, Jarlath E; Jones, Carroll; Sheoran, Abhineet S

2011-06-15

Leptospira interrogans serovar Copenhageni causes pulmonary hemorrhages with respiratory failure, a major cause of death in leptospirosis patients. Protective immunity to Leptospira is known to correlate with the production of leptospiral lipopolysaccharide (L-LPS)-specific agglutinating antibodies. We generated L-LPS-specific mouse monoclonal antibodies (MAbs) and investigated if these MAbs can protect guinea pigs against fatal pulmonary hemorrhages caused by serovar Copenhageni. The MAbs L8H4 and L9B11 against 22kDa L-LPS agglutinated leptospires and completely protected guinea pigs from the development of fatal pulmonary hemorrhages by serovar Copenhageni, whereas the MAb L4C1 against 8kDa L-LPS neither agglutinated the bacteria nor protected the animals against the fatal pulmonary hemorrhages. Copyright © 2011 Elsevier Ltd. All rights reserved.

Identification of the Streptococcus pyogenes surface antigens recognised by pooled human immunoglobulin

PubMed Central

Reglinski, Mark; Gierula, Magdalena; Lynskey, Nicola N.; Edwards, Robert J.; Sriskandan, Shiranee

2015-01-01

Immunity to common bacteria requires the generation of antibodies that promote opsonophagocytosis and neutralise toxins. Pooled human immunoglobulin is widely advocated as an adjunctive treatment for clinical Streptococcus pyogenes infection however, the protein targets of the reagent remain ill defined. Affinity purification of the anti-streptococcal antibodies present within pooled immunoglobulin resulted in the generation of an IgG preparation that promoted opsonophagocytic killing of S. pyogenes in vitro and provided passive immunity in vivo. Isolation of the streptococcal surface proteins recognised by pooled human immunoglobulin permitted identification and ranking of 94 protein antigens, ten of which were reproducibly identified across four contemporary invasive S. pyogenes serotypes (M1, M3, M12 and M89). The data provide novel insight into the action of pooled human immunoglobulin during invasive S. pyogenes infection, and demonstrate a potential route to enhance the efficacy of antibody based therapies. PMID:26508447

An Overview on the Field of Micro- and Nanotechnologies for Synthetic Peptide-Based Vaccines

PubMed Central

Salvador, Aiala; Igartua, Manoli; Hernández, Rosa Maria; Pedraz, José Luis

2011-01-01

The development of synthetic peptide-based vaccines has many advantages in comparison with vaccines based on live attenuated organisms, inactivated or killed organism, or toxins. Peptide-based vaccines cannot revert to a virulent form, allow a better conservation, and are produced more easily and safely. However, they generate a weaker immune response than other vaccines, and the inclusion of adjuvants and/or the use of vaccine delivery systems is almost always needed. Among vaccine delivery systems, micro- and nanoparticulated ones are attractive, because their particulate nature can increase cross-presentation of the peptide. In addition, they can be passively or actively targeted to antigen presenting cells. Furthermore, particulate adjuvants are able to directly activate innate immune system in vivo. Here, we summarize micro- and nanoparticulated vaccine delivery systems used in the field of synthetic peptide-based vaccines as well as strategies to increase their immunogenicity. PMID:21773041

Cancer nanoimmunotherapy using advanced pharmaceutical nanotechnology.

PubMed

Li, Wei; Wei, Huafeng; Li, Huafei; Gao, Jie; Feng, Si-Shen; Guo, Yajun

2014-11-01

Immunotherapy is a promising option for cancer treatment that might cure cancer with fewer side effects by primarily activating the host's immune system. However, the effect of traditional immunotherapy is modest, frequently due to tumor escape and resistance of multiple mechanisms. Pharmaceutical nanotechnology, which is also called cancer nanotechnology or nanomedicine, has provided a practical solution to solve the limitations of traditional immunotherapy. This article reviews the latest developments in immunotherapy and nanomedicine, and illustrates how nanocarriers (including micelles, liposomes, polymer-drug conjugates, solid lipid nanoparticles and biodegradable nanoparticles) could be used for the cellular transfer of immune effectors for active and passive nanoimmunotherapy. The fine engineering of nanocarriers based on the unique features of the tumor microenvironment and extra-/intra-cellular conditions of tumor cells can greatly tip the triangle immunobalance among host, tumor and nanoparticulates in favor of antitumor responses, which shows a promising prospect for nanoimmunotherapy.

[Tobacco smoke and risk of bacterial infection].

PubMed

Trosini-Desert, V; Germaud, P; Dautzenberg, B

2004-06-01

Tobacco smoke is a proven risk factor for bacterial infection. In adults without COPD, smoking is associated with a significant increase in the relative risk (RR) of pneumonia (RR=2.97; 95% CI 1.52-5.81), S pneumoniae pneumonia (RR=2.50; 95% IC 1.50-5.10), Legionella infection (RR=3.75; 95% CI 2.17-6.17). Smoking has clearly been shown to be associated with an increased risk of tuberculosis (RR=2.60; 95% CI 2,20-3,20), and also with increased incidence of post-operative infections. In young children whose parents smoke, passive exposure to tobacco smoke is associated with an increased relative risk of seasonal infections (RR=1.7; CI 95% 1.55-1.91) and recurrent otitis media (RR=1.48; 95% CI 1.08-2.04). Passive smoking also increases risk of pneumonia in adults (RR=2.5; CI 95% 1.2-5.1). Plausible explanations of the increased risk of infection in active or passive smokers include increased bacterial adherence, decrease of lung and nasal clearance, and changes in the immune response. Exposure to tobacco smoke approximately doubles the risk of infection. This increased burden of infection has significant healthcare cost implications. Each infectious episode in an individual should prompt an attempt at smoking cessation.

Anti-influenza Hyperimmune Immunoglobulin Enhances Fc-functional Antibody Immunity during Human Influenza Infection.

PubMed

Vanderven, Hillary A; Wragg, Kathleen; Ana-Sosa-Batiz, Fernanda; Kristensen, Anne B; Jegaskanda, Sinthujan; Wheatley, Adam K; Wentworth, Deborah; Wines, Bruce D; Hogarth, P Mark; Rockman, Steve; Kent, Stephen J

2018-05-31

New treatments for severe influenza are needed. Passive transfer of influenza-specific hyperimmune pooled immunoglobulin (Flu-IVIG) boosts neutralising antibody responses to past strains in influenza-infected subjects. The effect of Flu-IVIG on antibodies with Fc-mediated functions, which may target diverse influenza strains, is unclear. We studied the capacity of Flu-IVIG, relative to standard IVIG, to bind to Fc receptors and mediate antibody-dependent cellular cytotoxicity in vitro. The effect of Flu-IVIG infusion, compared to placebo infusion, was examined in serial plasma samples from 24 subjects with confirmed influenza infection in the INSIGHT FLU005 pilot study. Flu-IVIG contains higher concentrations of Fc-functional antibodies than IVIG against a diverse range of influenza hemagglutinins. Following infusion of Flu-IVIG into influenza-infected subjects, a transient increase in Fc-functional antibodies was present for 1-3 days against infecting and non-infecting strains of influenza. Flu-IVIG contains antibodies with Fc-mediated functions against influenza virus and passive transfer of Flu-IVIG increases anti-influenza Fc-functional antibodies in the plasma of influenza-infected subjects. Enhancement of Fc-functional antibodies to a diverse range of influenza strains suggests that Flu-IVIG infusion could prove useful in the context of novel influenza virus infections, when there may be minimal or no neutralising antibodies in the Flu-IVIG preparation.

Measles Humoral and Cell-Mediated Immunity in Children Aged 5–10 Years After Primary Measles Immunization Administered at 6 or 9 Months of Age

PubMed Central

Gans, Hayley A.; Yasukawa, Linda L.; Sung, Phillip; Sullivan, Barbara; DeHovitz, Ross; Audet, Susette; Beeler, Judy; Arvin, Ann M.

2013-01-01

Background. Given the high infant measles mortality rate, there is interest in whether a measles immunization regimen beginning at <12 months of age provides lasting immunity. Methods. Measles-specific immune responses were evaluated in 70 children aged 5–10 years after primary measles vaccine administered at 6, 9, or 12 months. Results. At 5–10 years of age, the stimulation index for measles T-cell proliferation was 11.4 (SE, 1.3), 10.9 (SE, 1.5), and 14.4 (SE 2.1) when the first measles dose was given at 6, 9, or 12 months, respectively. Neutralizing antibody concentration (geometric mean titer [GMT]) in those immunized at 6 months of age was 125 mIU/mL (95% confidence interval [CI], 42–377) in the presence of passive antibodies (PAs) and 335 mIU/mL (95% CI, 211–531) in those without PAs; in those immunized at 9 months, GMTs were 186 mIU/mL (95% CI, 103–335) and 1080 mIU/mL (95% CI, 642–1827) in the presence and absence of PAs, respectively. The GMT was 707 mIU/mL (95% CI, 456–1095) when vaccine was administered at 12 months (P ≤ .04). Conclusions. Measles-specific T-cell responses were sustained at 5–10 years of age regardless of age at time of primary measles immunization. Neutralizing antibody concentrations were lower in cohorts given the first vaccine dose at 6 months of age and in the presence of PAs; however, responses could be boosted by subsequent doses. Starting measles vaccination at <12 months of age may be beneficial during measles outbreaks or in endemic areas. PMID:23300162

Targeting the zona pellucida for immunocontraception: a minireview.

PubMed

Tesarik, J

1995-12-01

This minireview summarizes the main data relevant to the development of contraceptive vaccines based on zona pellucida (ZP) antigens, as well as the pros and the cons of this immunocontraceptive strategy. Even though the antifertility efficacy of anti-ZP antibodies in humans is not corroborated by a clear relationship between spontaneous autoimmunization against the ZP and infertility, passive and active immunization studies in laboratory animals have provided convincing results. The contraceptive action of anti-ZP antibodies, targeting events situated upstream of gamete fusion, is devoid of potential ethical concerns related to the destruction of early embryos. The high protein content of the mammalian ZP, knowledge of the complete amino acid sequence of the major ZP proteins, and the high degree of sequence homology between individual species all favour the rapid advancement of anti-ZP vaccine projects. However, certain sequences of ZP proteins, when incorporated into the vaccine construct, activate CD4+ T cells of the recipient organism to direct a cellular immune attack (autoimmune oophoritis) to other functionally relevant ovarian components (primordial follicles, steroidogenic cells). The search for the optimal combination of B cell and T cell epitopes in the vaccine construct will hopefully overcome this problem.

Clostridium difficile chimeric toxin receptor binding domain vaccine induced protection against different strains in active and passive challenge models.

PubMed

Tian, Jing-Hui; Glenn, Gregory; Flyer, David; Zhou, Bin; Liu, Ye; Sullivan, Eddie; Wu, Hua; Cummings, James F; Elllingsworth, Larry; Smith, Gale

2017-07-24

Clostridium difficile is the number one cause of nosocomial antibiotic-associated diarrhea in developed countries. Historically, pathogenesis was attributed two homologous glucosylating toxins, toxin-A (TcdA) and toxin-B (TcdB). Over the past decade, however, highly virulent epidemic strains of C. difficile (B1/NAP1/027) have emerged and are linked to an increase in morbidity and mortality. Increased virulence is attributed to multiple factors including: increased production of A- and B-toxins; production of binary toxin (CDT); and the emergence of more toxic TcdB variants (TcdB (027) ). TcdB (027) is more cytotoxicity to cells; causes greater tissue damage and toxicity in animals; and is antigenically distinct from historical TcdB (TcdB (003) ). Broadly protective vaccines and therapeutic antibody strategies, therefore, may target TcdA, TcdB variants and CDT. To facilitate the generation of multivalent toxin-based C. difficile vaccines and therapeutic antibodies, we have generated fusion proteins constructed from the receptor binding domains (RBD) of TcdA, TcdB (003) , TcdB (027) and CDT. Herein, we describe the development of a trivalent toxin (T-toxin) vaccine (CDTb/TcdB (003) /TcdA) and quadravalent toxin (Q-toxin) vaccine (CDTb/TcB (003) /TcdA/TcdB (027) ) fusion proteins that retain the protective toxin neutralizing epitopes. Active immunization of mice or hamsters with T-toxin or Q-toxin fusion protein vaccines elicited the generation of toxin neutralizing antibodies to each of the toxins. Hamsters immunized with the Q-toxin vaccine were broadly protected against spore challenge with historical C. difficile 630 (toxinotype 0/ribotype 003) and epidemic NAP1 (toxinotype III/ribotype 027) strains. Fully human polyclonal antitoxin IgG was produced by immunization of transgenic bovine with these fusion proteins. In passive transfer studies, mice were protected against lethal toxin challenge. Hamsters treated with human antitoxin IgG were completely protected when challenged with historical or epidemic strains of C. difficile. The use of chimeric fusion proteins is an attractive approach to producing multivalent antitoxin vaccines and therapeutic polyclonal antibodies for prevention and treatment of C. difficile infections (CDI). Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Immunization with a Vaccine Combining Herpes Simplex Virus 2 (HSV-2) Glycoprotein C (gC) and gD Subunits Improves the Protection of Dorsal Root Ganglia in Mice and Reduces the Frequency of Recurrent Vaginal Shedding of HSV-2 DNA in Guinea Pigs Compared to Immunization with gD Alone ▿

PubMed Central

Awasthi, Sita; Lubinski, John M.; Shaw, Carolyn E.; Barrett, Shana M.; Cai, Michael; Wang, Fushan; Betts, Michael; Kingsley, Susan; DiStefano, Daniel J.; Balliet, John W.; Flynn, Jessica A.; Casimiro, Danilo R.; Bryan, Janine T.; Friedman, Harvey M.

2011-01-01

Attempts to develop a vaccine to prevent genital herpes simplex virus 2 (HSV-2) disease have been only marginally successful, suggesting that novel strategies are needed. Immunization with HSV-2 glycoprotein C (gC-2) and gD-2 was evaluated in mice and guinea pigs to determine whether adding gC-2 to a gD-2 subunit vaccine would improve protection by producing antibodies that block gC-2 immune evasion from complement. Antibodies produced by gC-2 immunization blocked the interaction between gC-2 and complement C3b, and passive transfer of gC-2 antibody protected complement-intact mice but not C3 knockout mice against HSV-2 challenge, indicating that gC-2 antibody is effective, at least in part, because it prevents HSV-2 evasion from complement. Immunization with gC-2 also produced neutralizing antibodies that were active in the absence of complement; however, the neutralizing titers were higher when complement was present, with the highest titers in animals immunized with both antigens. Animals immunized with the gC-2-plus-gD-2 combination had robust CD4+ T-cell responses to each immunogen. Multiple disease parameters were evaluated in mice and guinea pigs immunized with gC-2 alone, gD-2 alone, or both antigens. In general, gD-2 outperformed gC-2; however, the gC-2-plus-gD-2 combination outperformed gD-2 alone, particularly in protecting dorsal root ganglia in mice and reducing recurrent vaginal shedding of HSV-2 DNA in guinea pigs. Therefore, the gC-2 subunit antigen enhances a gD-2 subunit vaccine by stimulating a CD4+ T-cell response, by producing neutralizing antibodies that are effective in the absence and presence of complement, and by blocking immune evasion domains that inhibit complement activation. PMID:21813597

Inactivation of the alpha C protein antigen gene, bca, by a novel shuttle/suicide vector results in attenuation of virulence and immunity in group B Streptococcus.

PubMed

Li, J; Kasper, D L; Ausubel, F M; Rosner, B; Michel, J L

1997-11-25

The alpha C protein of group B Streptococcus (GBS) is a major surface-associated antigen. Although its role in the biology and virulence of GBS has not been defined, it is opsonic and capable of eliciting protective immunity. The alpha C protein is widely distributed among clinical isolates and is a potential protein carrier and antigen in conjugate vaccines to prevent GBS infections. The structural gene for the alpha C protein, bca, has been cloned and sequenced. The protein encoded by bca is related to a class of surface-associated proteins of gram-positive cocci involved in virulence and immunity. To investigate the potential roles of the alpha C protein, bca null mutants were generated in which the bca gene was replaced with a kanamycin resistance cassette via homologous recombination using a novel shuttle/suicide vector. Studies of lethality in neonatal mice showed that the virulence of the bca null mutants was attenuated 5- to 7-fold when compared with the isogenic wild-type strain A909. Significant differences in mortality occurred in the first 24 h, suggesting that the role of the alpha antigen is important in the initial stages of the infection. In contrast to A909, bca mutants were no longer killed by polymorphonuclear leukocytes in the presence of alpha-specific antibodies in an in vitro opsonophagocytic assay. In contrast to previous studies, alpha antigen expression does not appear to play a role in resistance to opsonophagocytosis in the absence of alpha-specific antibodies. In addition, antibodies to the alpha C protein did not passively protect neonatal mice from lethal challenge with bca mutants, suggesting that these epitopes are uniquely present within the alpha antigen as expressed from the bca gene. Therefore, the alpha C protein is important in the pathogenesis of GBS infection and is a target for protective immunity in the development of GBS vaccines.

Venom conjugated polylactide applied as biocompatible material for passive and active immunotherapy against scorpion envenomation.

PubMed

Ayari-Riabi, Sana; Trimaille, Thomas; Mabrouk, Kamel; Bertin, Denis; Gigmes, Didier; Benlasfar, Zakaria; Zaghmi, Ahlem; Bouhaouala-Zahar, Balkiss; Elayeb, Mohamed

2016-04-04

Scorpion envenoming represents a public health issue in subtropical regions of the world. Treatment and prevention need to promote antitoxin immunity. Preserving antigenic presentation while removing toxin effect remains a major challenge in toxin vaccine development. Among particulate adjuvant, particles prepared with poly (D,L-lactide) polymer are the most extensively investigated due to their excellent biocompatibility and biodegradability. The aim of this study is to develop surfactant-free PLA nanoparticles that safely deliver venom toxic fraction to enhance specific immune response. PLA nanoparticles are coated with AahG50 (AahG50/PLA) and BotG50 (BotG50/PLA): a toxic fraction purified from Androctonus australis hector and Buthus occitanus tunetanus venoms, respectively. Residual toxicities are evaluated following injections of PLA-containing high doses of AahG50 (or BotG50). Immunization trials are performed with the detoxified fraction administered alone without adjuvant. A comparative study of the effect of Freund is also included. The neutralizing capacity of sera is determined in naive mice. Six months later, immunized mice are challenged subcutaneously with increased doses of AahG50. Subcutaneous lethal dose 50 (LD50) of AahG50 and BotG50 is of 575 μg/kg and 1300 μg/kg respectively. By comparison, BotG50/PLA is totally innocuous while 50% of tested mice survive 2875 μg AahG50/kg. Alhydrogel and Freund are not able to detoxify such a high dose. Cross-antigenicity between particulate and soluble fraction is also, ensured. AahG50/PLA and BotG50/PLA induce high antibody levels in mice serum. The neutralizing capacity per mL of anti-venom was 258 μg/mL and 186 μg/mL calculated for anti-AahG50/PLA and anti-BotG50/PLA sera, respectively. Animals immunized with AahG50/PLA are protected against AahG50 injected dose of 3162 μg/kg as opposed all non-immunized mice died at this dose. We find that the detoxification approach based PLA nanoparticles, benefit the immunogenicity and protective efficacy of venom immunogen. Copyright © 2016 Elsevier Ltd. All rights reserved.

Evaluation of Quantitative Anti-F1 IgG and Anti-V IgG ELISAs for use as an in Vitro-Based Potency Assay of Plague Vaccine in Mice

DTIC Science & Technology

2008-04-01

Andrews GP, Welkos SL, Friedlander AM, et al. Protection of mice from fatal bubonic and pneu- monic plague by passive immunization with monoclonal...SL, Andrews GP, Adamovicz J, et al. Protection against experimental bubonic and pneumonic plague by a recombinant capsular F1-V antigen fusion...fusion protein as vaccine antigen against bubonic and pneumonic plague . Biotechnol Prog 2005; 21:1490e510.[21] Simpson WJ, Thomas RE, Schwan TG

Protective effects of a Modified Vaccinia Ankara-based vaccine candidate against Crimean-Congo Haemorrhagic Fever virus require both cellular and humoral responses.

PubMed

Dowall, Stuart D; Graham, Victoria A; Rayner, Emma; Hunter, Laura; Watson, Robert; Taylor, Irene; Rule, Antony; Carroll, Miles W; Hewson, Roger

2016-01-01

Crimean-Congo Haemorrhagic Fever (CCHF) is a severe tick-borne disease, endemic in many countries in Africa, the Middle East, Eastern Europe and Asia. There is no approved vaccine currently available against CCHF. The most promising candidate, which has previously been shown to confer protection in the small animal model, is a modified Vaccinia Ankara virus vector expressing the CCHF viral glycoprotein (MVA-GP). It has been shown that MVA-GP induces both humoral and cellular immunogenicity. In the present study, sera and T-lymphocytes were passively and adoptively transferred into recipient mice prior to challenge with CCHF virus. Results demonstrated that mediators from both arms of the immune system were required to demonstrate protective effects against lethal challenge.

Protective effects of a Modified Vaccinia Ankara-based vaccine candidate against Crimean-Congo Haemorrhagic Fever virus require both cellular and humoral responses

PubMed Central

Dowall, Stuart D.; Graham, Victoria A.; Rayner, Emma; Hunter, Laura; Watson, Robert; Taylor, Irene; Rule, Antony; Carroll, Miles W.; Hewson, Roger

2016-01-01

Crimean-Congo Haemorrhagic Fever (CCHF) is a severe tick-borne disease, endemic in many countries in Africa, the Middle East, Eastern Europe and Asia. There is no approved vaccine currently available against CCHF. The most promising candidate, which has previously been shown to confer protection in the small animal model, is a modified Vaccinia Ankara virus vector expressing the CCHF viral glycoprotein (MVA-GP). It has been shown that MVA-GP induces both humoral and cellular immunogenicity. In the present study, sera and T-lymphocytes were passively and adoptively transferred into recipient mice prior to challenge with CCHF virus. Results demonstrated that mediators from both arms of the immune system were required to demonstrate protective effects against lethal challenge. PMID:27272940

Bezlotoxumab: anti-toxin B monoclonal antibody to prevent recurrence of Clostridium difficile infection.

PubMed

Villafuerte Gálvez, Javier A; Kelly, Ciarán P

2017-07-01

Clostridium difficile infection (CDI) is the most common nosocomial infection in the U.S. 25% of CDI patients go on to develop recurrent CDI (rCDI) following current standard of care (SOC) therapy, leading to morbidity, mortality and economic loss. The first passive immunotherapy drug targeting C.difficile toxin B (bezlotoxumab) has been approved recently by the FDA and EMA for prevention of rCDI. Areas covered: A body of key studies was selected and reviewed by the authors. The unmet needs in CDI care were ascertained with emphasis in rCDI, including the epidemiology, pathophysiology and current management. The current knowledge about the immune response to C. difficile toxins and how this knowledge led to the development and the clinical use of bezlotoxumab is described. Current and potential future competitors to the drug were examined. Expert commentary: A single 10 mg/kg intravenous infusion of bezlotoxumab has been shown to decrease rCDI by ~40% (absolute reduction ~10%) in patients being treated for primary CDI or rCDI with SOC antibiotics. Targeting C.difficile toxins by passive immunotherapy is a novel mechanism for prevention of C.difficile infection. Bezlotoxumab will be a valuable adjunctive therapy to reduce the burden of CDI.

Active and passive surveillance of enoxaparin generics: a case study relevant to biosimilars.

PubMed

Grampp, Gustavo; Bonafede, Machaon; Felix, Thomas; Li, Edward; Malecki, Michael; Sprafka, J Michael

2015-03-01

This retrospective analysis assessed the capability of active and passive safety surveillance systems to track product-specific safety events in the USA for branded and generic enoxaparin, a complex injectable subject to immune-related and other adverse events (AEs). Analysis of heparin-induced thrombocytopenia (HIT) incidence was performed on benefit claims for commercial and Medicare supplemental-insured individuals newly treated with enoxaparin under pharmacy benefit (1 January 2009 - 30 June 2012). Additionally, spontaneous reports from the FDA AE Reporting System were reviewed to identify incidence and attribution of enoxaparin-related reports to specific manufacturers. Specific, dispensed products were identifiable from National Drug Codes only in pharmacy-benefit databases, permitting sensitive comparison of HIT incidence in nearly a third of patients treated with brand or generic enoxaparin. After originator medicine's loss of exclusivity, only 5% of spontaneous reports were processed by generic manufacturers; reports attributable to specific generics were approximately ninefold lower than expected based on market share. Claims data were useful for active surveillance of enoxaparin generics dispensed under pharmacy benefits but not for products administered under medical benefits. These findings suggest that the current spontaneous reporting system will not distinguish product-specific safety signals for products distributed by multiple manufacturers, including biosimilars.

Vaccine and Monoclonal Antibody That Enhance Mouse Resistance to Candidiasis ▿

PubMed Central

Xin, Hong; Cutler, Jim E.

2011-01-01

Previously we showed that antibodies specific for the glycan β-1,2-mannotriose [β-(Man)3] on the cell surface of Candida albicans protect mice against disseminated candidiasis (H. Xin, S. Dziadek, D. R. Bundle, and J. E. Cutler, Proc. Natl. Acad. Sci. U. S. A. 105:13526–13531, 2008). Furthermore, six 14-mer peptides that are within the N-terminal portion of C. albicans wall proteins were conjugated to the glycan in an attempt to create immunogenic glycopeptide conjugates. By a dendritic cell (DC)-based immunization approach, all were immunogenic and three of the six conjugates induced a high degree of protection in mice. Interestingly, whereas all six peptides induced antibody responses when used alone to pulse DCs for subsequent immunizations, three peptides induced protection, and one in particular, peptide Fba (derived from fructose-bisphosphate aldolase), induced robust protective responses and is the focus of the current work. Fba peptide is not restricted by the major histocompatibility complex class II (MHC-II), as it induced anti-Fba antibodies in mice of different H-2 haplotypes and in rabbits. Furthermore, the peptide induced protection against disease caused by different C. albicans strains. Partial protection was achieved when alum was used in place of DCs for Fba immunizations. The passive transfer of immune sera from Fba-vaccinated mice, but not immune serum preabsorbed with fungal cells, conferred protection in naïve mice. This result, along with our finding that a monoclonal antibody specific for the peptide, E2-9 (IgM), protected mice against candidiasis, provide strong evidence that antibodies contribute to protection. Our work demonstrates the utility of cell wall peptides alone or as glycopeptides in vaccines designed for the induction of immunity against candidiasis and monoclonal antibodies as a rapid immunoprotective approach against the disease. PMID:21832099

Experimental and Field Results Regarding Immunity Induced by a Recombinant Turkey Herpesvirus H5 Vector Vaccine Against H5N1 and Other H5 Highly Pathogenic Avian Influenza Virus Challenges.

PubMed

Gardin, Yannick; Palya, Vilmos; Dorsey, Kristi Moore; El-Attrache, John; Bonfante, Francesco; Wit, Sjaak de; Kapczynski, Darrell; Kilany, Walid Hamdy; Rauw, Fabienne; Steensels, Mieke; Soejoedono, Retno D

2016-05-01

Vaccination against H5N1 highly pathogenic avian influenza (AI) virus (HPAIV) is one of the possible complementary means available for affected countries to control AI when the disease has become, or with a high risk of becoming, endemic. Efficacy of the vaccination against AI relies essentially, but not exclusively, on the capacity of the vaccine to induce immunity against the targeted virus (which is prone to undergo antigenic variations), as well as its capacity to overcome interference with maternal immunity transmitted by immunized breeding hens to their progeny. This property of the vaccine is a prerequisite for its administration at the hatchery, which assures higher and more reliable vaccine coverage of the populations than vaccination at the farm. A recombinant vector vaccine (Vectormune® AI), based on turkey herpesvirus expressing the hemagglutinin gene of an H5N1 HPAIV as an insert, has been used in several experiments conducted in different research laboratories, as well as in controlled field trials. The results have demonstrated a high degree of homologous and cross protection against different genetic clades of the H5N1 HPAIV. Furthermore, vaccine-induced immunity was not impaired by the presence of passive immunity, but on the contrary, cumulated with it for improved early protection. The demonstrated levels of protection against the different challenge viruses exhibited variations in terms of postchallenge mortality, as well as challenge virus shedding. The data presented here highlight the advantages of this vaccine as a useful and reliable tool to complement biosecurity and sanitary policies for better controlling the disease due to HPAIV of H5 subtypes, when the vaccination is applied as a control measure.

Protective Immunity to Ricin Toxin Conferred by Antibodies against the Toxin’s Binding Subunit (RTB)

PubMed Central

Yermakova, Anastasiya; Mantis, Nicholas J.

2011-01-01

The B subunit (RTB) of ricin toxin is a galactose-/N-acetyl galactosamine-specific lectin that promotes attachment and entry of ricin into host cells. RTB is also the archetype of the so-called R-type lectin family, whose members include haemagglutinins of botulinum neurotoxin (BoNT) progenitor toxins, as well as the binding subunits of cytolethal distending toxins. Although RTB is an appealing subunit vaccine candidate, as well as a potential target for immunotherapeutics, the degree to which RTB immunization elicits protective antibodies against ricin toxin remains unresolved. To address this issue, groups of mice were immunized with RTB and then challenged with 5xLD50s of ricin administered intraperitoneally. Despite high RTB-specific serum antibody titers, groups of RTB immunized mice were only partially immune to ricin challenge. Analysis of a collection of RTB-specific B cell hybridomas suggested that only a small fraction of antibodies against RTB have demonstrable neutralizing activity. Two RTB-specific neutralizing monoclonal IgG1 antibodies, 24B11 and SylH3, when passively administered to mice, were sufficient to protect the animals against a 5xLD50 dose of ricin. Both 24B11 and SylH3 blocked ricin attachment to terminal galactose residues and prevented toxin binding to the surfaces of bone marrow-derived macrophages (BMM), suggesting that they function by steric hindrance and recognize epitopes located on RTB’s carbohydrate recognition sub-domains (1α or 2γ). These data raise the possibility of using specific RTB sub-domains, rather than RTB itself, as antigens to more efficiently elicit neutralizing antibodies and protective immunity against ricin. PMID:21872634

A droplet-merging platform for comparative functional analysis of m1 and m2 macrophages in response to e. coli-induced stimuli.

PubMed

Hondroulis, Evangelia; Movila, Alexandru; Sabhachandani, Pooja; Sarkar, Saheli; Cohen, Noa; Kawai, Toshihisa; Konry, Tania

2017-03-01

Microfluidic droplets are used to isolate cell pairs and prevent crosstalk with neighboring cells, while permitting free motility and interaction within the confined space. Dynamic analysis of cellular heterogeneity in droplets has provided insights in various biological processes. Droplet manipulation methods such as fusion and fission make it possible to precisely regulate the localized environment of a cell in a droplet and deliver reagents as required. Droplet fusion strategies achieved by passive mechanisms preserve cell viability and are easier to fabricate and operate. Here, we present a simple and effective method for the co-encapsulation of polarized M1 and M2 macrophages with Escherichia coli (E. coli) by passive merging in an integrated droplet generation, merging, and docking platform. This approach facilitated live cell profiling of effector immune functions in situ and quantitative functional analysis of macrophage heterogeneity. Biotechnol. Bioeng. 2017;114: 705-709. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Identification of Cardiometabolic Vulnerabilities Caused by Effects of Synergistic Stressors that are Commonly Encountered During Space Missions

NASA Technical Reports Server (NTRS)

Ruger, M.; Scheer, F. A. J.; Barger, L. K.; Lockley, S. W.; Wang, W.; Johnston, S. L. III; Crucian, B.; Shea, A. S.

2011-01-01

Microgravity is a physiologically challenging state even when at rest. Astronauts experience additional physical and mental stresses, such as prolonged exertion, sleep loss and circadian misalignment, that could impact cardiovascular function. The main goals of this four year NASA project are to characterize the independent and synergistic effects on cardiovascular and immune function of: (1) circadian misalignment; (2) sleep loss; and (3) varied physical and mental stressors, mimicking some of the synergistic stressors experienced by astronauts. Sixteen healthy volunteers, aged 35-55 years, will be studied with standardized behavioral stressors occurring across all circadian phases, both with and without accruing sleep loss, achieved via two 11-day "forced desynchrony" protocols performed in each subject (randomized, within-subject design), where wake periods are advanced 4-h each "day" (i.e. recurring 20-h "days"). One protocol permits 8.33 h sleep opportunity per 20-h "day" (=10 h sleep per 24-h), and the other permits 5 h sleep per 20-h "day" (=6 h sleep per 24-h; matching the reported sleep duration of astronauts). In both protocols, subjects will perform a standardized stress battery including a cognitively challenging task; bicycle exercise, and passive 60deg head up tilt. Outcome variables include blood pressure, heart rate, arrhythmia frequency, cardiac vagal tone (from heart rate variability), sympathetic activity (catecholamines), and endothelial function. Additional measures of cardiac function (echocardiography), responses to a passive 80deg head up tilt, maximal oxygen uptake, and immune function will be assessed at the beginning and at the end of each protocol (i.e., without and with sleep loss, and before and after circadian misalignment). We hope to identify the relative impact on cardiovascular risk markers of varied behavioural stressors while subjects experience circadian misalignment and sleep loss, mimicking some of the synergistic stressors experienced by astronauts. Supported by NASANNX1 OAR 1 OG.

Passive immunization against highly pathogenic Avian Influenza Virus (AIV) strain H7N3 with antiserum generated from viral polypeptides protect poultry birds from lethal viral infection

PubMed Central

Shahzad, Mirza Imran; Naeem, Khalid; Mukhtar, Muhammad; Khanum, Azra

2008-01-01

Our studies were aimed at developing a vaccination strategy that could provide protection against highly pathogenic avian influenza virus (AIV), H7N3 or its variants outbreaks. A purified viral stock of highly pathogenic H7N3 isolate was lysed to isolate viral proteins by electrophresing on 12% sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), followed by their elution from gel through trituration in phosphate buffered saline (PBS). Overall, five isolated viral polypeptides/proteins upon characterization were used to prepare hyperimmune monovalent serum against respective polypeptides independently and a mixture of all five in poultry birds, and specificity confirmation of each antiserum through dot blot and Western blotting. Antiserum generated from various group birds was pooled and evaluated in 2-week old broiler chicken, for its protection against viral challenge. To evaluate in-vivo protection of each antiserum against viral challenges, six groups of 2-week old broiler chicken were injected with antiserum and a seventh control group received normal saline. Each group was exposed to purified highly pathogenic AIV H7N3 strain at a dose 105 embryo lethal dose (ELD50). We observed that nucleoprotein (NP) antiserum significantly protected birds from viral infection induced morbidity, mortality and lowered viral shedding compared with antiserum from individual viral proteins or mixed polypeptides/proteins inclusive of NP component. The capability of individual viral polypeptide specific antisera to protect against viral challenges in decreasing order was nucleoprotein (NP) > hemagglutinin (HA) > neuraminidase (NA) > viral proteins mix > viral polymerase (PM) > non-structural proteins (NS). Our data provide proof of concept for potential utilization of passive immunization in protecting poultry industry during infection outbreaks. Furthermore conserved nature of avian NP makes it an ideal candidate to produce antiserum protective against viral infection. PMID:19040734

The Bruton tyrosine kinase inhibitor PCI-32765 ameliorates autoimmune arthritis by inhibition of multiple effector cells

PubMed Central

2011-01-01

Introduction The aim was to determine the effect of the Bruton tyrosine kinase (Btk)-selective inhibitor PCI-32765, currently in Phase I/II studies in lymphoma trials, in arthritis and immune-complex (IC) based animal models and describe the underlying cellular mechanisms. Methods PCI-32765 was administered in a series of murine IC disease models including collagen-induced arthritis (CIA), collagen antibody-induced arthritis (CAIA), reversed passive anaphylactic reaction (RPA), and passive cutaneous anaphylaxis (PCA). Clinical and pathologic features characteristic of each model were examined following treatment. PCI-32765 was then examined in assays using immune cells relevant to the pathogenesis of arthritis, and where Btk is thought to play a functional role. These included proliferation and calcium mobilization in B cells, cytokine and chemokine production in monocytes/macrophages, degranulation of mast cells and its subsequent cytokine/chemokine production. Results PCI-32765 dose-dependently and potently reversed arthritic inflammation in a therapeutic CIA model with an ED50 of 2.6 mg/kg/day. PCI-32765 also prevented clinical arthritis in CAIA models. In both models, infiltration of monocytes and macrophages into the synovium was completely inhibited and importantly, the bone and cartilage integrity of the joints were preserved. PCI-32765 reduced inflammation in the Arthus and PCA assays. In vitro, PCI-32765 inhibited BCR-activated primary B cell proliferation (IC50 = 8 nM). Following FcγR stimulation, PCI-32765 inhibited TNFα, IL-1β and IL-6 production in primary monocytes (IC50 = 2.6, 0.5, 3.9 nM, respectively). Following FcεRI stimulation of cultured human mast cells, PCI-32765 inhibited release of histamine, PGD2, TNF-α, IL-8 and MCP-1. Conclusions PCI-32765 is efficacious in CIA, and in IC models that do not depend upon autoantibody production from B cells. Thus PCI-32765 targets not only B lymphocytes but also monocytes, macrophages and mast cells, which are important Btk-expressing effector cells in arthritis. PMID:21752263

A prospective study of the incidence of myocarditis/pericarditis and new onset cardiac symptoms following smallpox and influenza vaccination

DOE Office of Scientific and Technical Information (OSTI.GOV)

Engler, Renata J. M.; Nelson, Michael R.; Collins Jr., Limone C.

Although myocarditis/pericarditis (MP) has been identified as an adverse event following smallpox vaccine (SPX), the prospective incidence of this reaction and new onset cardiac symptoms, including possible subclinical injury, has not been prospectively defined. The study's primary objective was to determine the prospective incidence of new onset cardiac symptoms, clinical and possible subclinical MP in temporal association with immunization. New onset cardiac symptoms, clinical MP and cardiac specific troponin T (cTnT) elevations following SPX (above individual baseline values) were measured in a multi-center prospective, active surveillance cohort study of healthy subjects receiving either smallpox vaccine or trivalent influenza vaccine (TIV).more » Results New onset chest pain, dyspnea, and/or palpitations occurred in 10.6% of SPX-vaccinees and 2.6% of TIV-vaccinees within 30 days of immunization (relative risk (RR) 4.0, 95% CI: 1.7-9.3). Among the 1081 SPX-vaccinees with complete follow-up, 4 Caucasian males were diagnosed with probable myocarditis and 1 female with suspected pericarditis. This indicates a post-SPX incidence rate more than 200-times higher than the pre-SPX background population surveillance rate of myocarditis/pericarditis (RR 214, 95% CI 65-558). Additionally, 31 SPX-vaccinees without specific cardiac symptoms were found to have over 2-fold increases in cTnT (>99th percentile) from baseline (pre-SPX) during the window of risk for clinical myocarditis/pericarditis and meeting a proposed case definition for possible subclinical myocarditis. This rate is 60-times higher than the incidence rate of overt clinical cases. No clinical or possible subclinical myocarditis cases were identified in the TIV-vaccinated group. In conclusion, passive surveillance significantly underestimates the true incidence of myocarditis/pericarditis after smallpox immunization. Evidence of subclinical transient cardiac muscle injury post-vaccinia immunization is a finding that requires further study to include long-term outcomes surveillance. Active safety surveillance is needed to identify adverse events that are not well understood or previously recognized.« less

A prospective study of the incidence of myocarditis/pericarditis and new onset cardiac symptoms following smallpox and influenza vaccination

DOE PAGES

Engler, Renata J. M.; Nelson, Michael R.; Collins Jr., Limone C.; ...

2015-03-20

Although myocarditis/pericarditis (MP) has been identified as an adverse event following smallpox vaccine (SPX), the prospective incidence of this reaction and new onset cardiac symptoms, including possible subclinical injury, has not been prospectively defined. The study's primary objective was to determine the prospective incidence of new onset cardiac symptoms, clinical and possible subclinical MP in temporal association with immunization. New onset cardiac symptoms, clinical MP and cardiac specific troponin T (cTnT) elevations following SPX (above individual baseline values) were measured in a multi-center prospective, active surveillance cohort study of healthy subjects receiving either smallpox vaccine or trivalent influenza vaccine (TIV).more » Results New onset chest pain, dyspnea, and/or palpitations occurred in 10.6% of SPX-vaccinees and 2.6% of TIV-vaccinees within 30 days of immunization (relative risk (RR) 4.0, 95% CI: 1.7-9.3). Among the 1081 SPX-vaccinees with complete follow-up, 4 Caucasian males were diagnosed with probable myocarditis and 1 female with suspected pericarditis. This indicates a post-SPX incidence rate more than 200-times higher than the pre-SPX background population surveillance rate of myocarditis/pericarditis (RR 214, 95% CI 65-558). Additionally, 31 SPX-vaccinees without specific cardiac symptoms were found to have over 2-fold increases in cTnT (>99th percentile) from baseline (pre-SPX) during the window of risk for clinical myocarditis/pericarditis and meeting a proposed case definition for possible subclinical myocarditis. This rate is 60-times higher than the incidence rate of overt clinical cases. No clinical or possible subclinical myocarditis cases were identified in the TIV-vaccinated group. In conclusion, passive surveillance significantly underestimates the true incidence of myocarditis/pericarditis after smallpox immunization. Evidence of subclinical transient cardiac muscle injury post-vaccinia immunization is a finding that requires further study to include long-term outcomes surveillance. Active safety surveillance is needed to identify adverse events that are not well understood or previously recognized.« less

Transfer of Anti-Rotavirus Antibodies during Pregnancy and in Milk Following Maternal Vaccination with a Herpes Simplex Virus Type-1 Amplicon Vector.

PubMed

Meier, Anita F; Suter, Mark; Schraner, Elisabeth M; Humbel, Bruno M; Tobler, Kurt; Ackermann, Mathias; Laimbacher, Andrea S

2017-02-16

Rotaviruses (RVs) are important enteric pathogens of newborn humans and animals, causing diarrhea and in rare cases death, especially in very young individuals. Rotavirus vaccines presently used are modified live vaccines that lack complete biological safety. Previous work from our laboratory suggested that vaccines based on in situ produced, non-infectious rotavirus-like particles (RVLPs) are efficient while being entirely safe. However, using either vaccine, active mucosal immunization cannot induce protective immunity in newborns due to their immature immune system. We therefore hypothesized that offspring from vaccinated dams are passively immunized either by transfer of maternal antibodies during pregnancy or by taking up antibodies from milk. Using a codon optimized polycistronic gene expression cassette packaged into herpesvirus particles, the simultaneous expression of the RV capsid genes led to the intracellular formation of RVLPs in various cell lines. Vaccinated dams developed a strong RV specific IgG antibody response determined in sera and milk of both mother and pups. Moreover, sera of naïve pups nursed by vaccinated dams also had RV specific antibodies suggesting a lactogenic transfer of antibodies. Although full protection of pups was not achieved in this mouse model, our observations are important for the development of improved vaccines against RV in humans as well as in various animal species.

Transfer of Anti-Rotavirus Antibodies during Pregnancy and in Milk Following Maternal Vaccination with a Herpes Simplex Virus Type-1 Amplicon Vector

PubMed Central

Meier, Anita F.; Suter, Mark; Schraner, Elisabeth M.; Humbel, Bruno M.; Tobler, Kurt; Ackermann, Mathias; Laimbacher, Andrea S.

2017-01-01

Rotaviruses (RVs) are important enteric pathogens of newborn humans and animals, causing diarrhea and in rare cases death, especially in very young individuals. Rotavirus vaccines presently used are modified live vaccines that lack complete biological safety. Previous work from our laboratory suggested that vaccines based on in situ produced, non-infectious rotavirus-like particles (RVLPs) are efficient while being entirely safe. However, using either vaccine, active mucosal immunization cannot induce protective immunity in newborns due to their immature immune system. We therefore hypothesized that offspring from vaccinated dams are passively immunized either by transfer of maternal antibodies during pregnancy or by taking up antibodies from milk. Using a codon optimized polycistronic gene expression cassette packaged into herpesvirus particles, the simultaneous expression of the RV capsid genes led to the intracellular formation of RVLPs in various cell lines. Vaccinated dams developed a strong RV specific IgG antibody response determined in sera and milk of both mother and pups. Moreover, sera of naïve pups nursed by vaccinated dams also had RV specific antibodies suggesting a lactogenic transfer of antibodies. Although full protection of pups was not achieved in this mouse model, our observations are important for the development of improved vaccines against RV in humans as well as in various animal species. PMID:28212334

Epitope-Specific Suppression of IgG Responses by Passively Administered Specific IgG: Evidence of Epitope Masking.

PubMed

Bergström, Joakim J E; Xu, Hui; Heyman, Birgitta

2017-01-01

Specific IgG, passively administered together with particulate antigen, can completely prevent induction of antibody responses to this antigen. The ability of IgG to suppress antibody responses to sheep red blood cells (SRBCs) is intact in mice lacking FcγRs, complement factor 1q, C3, or complement receptors 1 and 2, suggesting that Fc-dependent effector functions are not involved. Two of the most widely discussed explanations for the suppressive effect are increased clearance of IgG-antigen complexes and/or that IgG "hides" the antigen from recognition by specific B cells, so-called epitope masking. The majority of data on how IgG induces suppression was obtained through studies of the effects on IgM-secreting single spleen cells during the first week after immunization. Here, we show that IgG also suppresses antigen-specific extrafollicular antibody-secreting cells, germinal center B-cells, long-lived plasma cells, long-term IgG responses, and induction of memory antibody responses. IgG anti-SRBC reduced the amount of SRBC in the spleens of wild-type, but not of FcγR-deficient mice. However, no correlation between suppression and the amount of SRBC in the spleen was observed, suggesting that increased clearance does not explain IgG-mediated suppression. Instead, we found compelling evidence for epitope masking because IgG anti-NP administered with NP-SRBC suppressed the IgG anti-NP, but not the IgG anti-SRBC response. Vice versa, IgG anti-SRBC administered with NP-SRBC, suppressed only the IgG anti-SRBC response. In conclusion, passively transferred IgG suppressed all measured parameters of an antigen-specific antibody/B cell response and an important mechanism of action is likely to be epitope masking.

Invited review: heat stress effects during late gestation on dry cows and their calves.

PubMed

Tao, S; Dahl, G E

2013-07-01

In dairy cattle, late gestation is a critical period for fetal growth and physiological transition into the next lactation. Environmental factors, such as temperature and light, exert dramatic effects on the production, health, and well-being of animals during this period and after parturition. The aim of this review was to introduce effects of heat stress during late gestation on dairy cattle, and discuss the biological mechanisms that underlie the observed production and health responses in the dam and her fetus. Relative to cooled cows, cows that are heat stressed during late gestation have impaired mammary growth before parturition and decreased milk production in the subsequent lactation. In response to higher milk yield, cows cooled prepartum undergo a series of homeorhetic adaptations in early lactation to meet higher demand for milk synthesis compared with heat-stressed cows, but no direct effect of environmental heat stress on metabolism exists during the dry period. Prepartum cooling improves immune status of transition cows and evidence suggests that altered prolactin signaling in immune cells mediates the effects of heat stress on immune function. Late-gestation heat stress compromises placental development, which results in fetal hypoxia, malnutrition, and eventually fetal growth retardation. Maternal heat stress may also have carryover effects on the postnatal growth of offspring, but direct evidence is still lacking. Emerging evidence suggests that offspring from prepartum heat-stressed cows have compromised passive immunity and impaired cell-mediated immune function compared with those from cooled cows. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Protective efficacy of passive immunization with monoclonal antibodies in animal models of H5N1 highly pathogenic avian influenza virus infection.

PubMed

Itoh, Yasushi; Yoshida, Reiko; Shichinohe, Shintaro; Higuchi, Megumi; Ishigaki, Hirohito; Nakayama, Misako; Pham, Van Loi; Ishida, Hideaki; Kitano, Mitsutaka; Arikata, Masahiko; Kitagawa, Naoko; Mitsuishi, Yachiyo; Ogasawara, Kazumasa; Tsuchiya, Hideaki; Hiono, Takahiro; Okamatsu, Masatoshi; Sakoda, Yoshihiro; Kida, Hiroshi; Ito, Mutsumi; Quynh Mai, Le; Kawaoka, Yoshihiro; Miyamoto, Hiroko; Ishijima, Mari; Igarashi, Manabu; Suzuki, Yasuhiko; Takada, Ayato

2014-06-01

Highly pathogenic avian influenza (HPAI) viruses of the H5N1 subtype often cause severe pneumonia and multiple organ failure in humans, with reported case fatality rates of more than 60%. To develop a clinical antibody therapy, we generated a human-mouse chimeric monoclonal antibody (MAb) ch61 that showed strong neutralizing activity against H5N1 HPAI viruses isolated from humans and evaluated its protective potential in mouse and nonhuman primate models of H5N1 HPAI virus infections. Passive immunization with MAb ch61 one day before or after challenge with a lethal dose of the virus completely protected mice, and partial protection was achieved when mice were treated 3 days after the challenge. In a cynomolgus macaque model, reduced viral loads and partial protection against lethal infection were observed in macaques treated with MAb ch61 intravenously one and three days after challenge. Protective effects were also noted in macaques under immunosuppression. Though mutant viruses escaping from neutralization by MAb ch61 were recovered from macaques treated with this MAb alone, combined treatment with MAb ch61 and peramivir reduced the emergence of escape mutants. Our results indicate that antibody therapy might be beneficial in reducing viral loads and delaying disease progression during H5N1 HPAI virus infection in clinical cases and combined treatment with other antiviral compounds should improve the protective effects of antibody therapy against H5N1 HPAI virus infection.

A Randomized Clinical Trial Evaluating the Effects of Oligosaccharides on Transfer of Passive Immunity in Neonatal Dairy Calves.

PubMed

Short, D M; Moore, D A; Sischo, W M

2016-07-01

Bacterial contamination of colostrum is common and can decrease IgG absorption in neonatal calves. Strategies that mitigate this situation without complicating colostrum management will benefit dairy calf health and survival. To evaluate the effects of supplementing colostrum with oligosaccharides (OS) on serum IgG concentration and apparent efficiency of absorption of IgG (AEA%) in calves fed unpasteurized colostrum and characterize these outcomes with respect to colostrum bacterial exposures. One hundred twenty-three neonatal dairy calves. Randomized, blinded, controlled clinical trial conducted at a commercial dairy operation. Calves were enrolled at birth in 1 of 4 treatment groups. Data were complete for 123 calves, which were distributed across the treatment groups as follows: mannan-oligosaccharides (MOS), n = 33; Saccharomyces galacto-oligosaccharides (SGOS), n = 31; Bifidobacterium galacto-oligosaccharides (BGOS), n = 28; and lactose control (CON), n = 31. A commercial radial immunodiffusion kit was used to determine colostrum and serum IgG concentrations. Conventional microbiology methods were used to enumerate colostrum bacterial counts. Bacterial counts were not significantly different among treatment groups. Total bacterial plate counts (TPC) were relatively low for the majority of colostrum samples, but TPC had a significant negative effect on serum IgG concentration and AEA% in the lactose-supplemented control group but not the OS treatment groups. These results suggest that a complement of OS structures may mitigate adverse effects of bacteria on transfer of passive immunity (TPI). Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

[Incidence of admissions due to pneumonia in children under 24 months old before and after the introduction of the 10-valent pneumococcal conjugate vaccine into the National Immunization Program of Chile].

PubMed

Fernández V, José Pablo; Goecke H, Carola; von Borries, Cecilia; Tapia R, Natalia; Santolaya de P, María Elena

2015-01-01

Streptococcus pneumoniae is the leading cause of bacterial pneumonia in children, especially in the hospitalized population. The 10-valent pneumococcal vaccine was included in the National Immunization Program of Chile in 2011. This study aims to evaluate the incidence of pneumonia in hospitalized children<24 months of age in the Luis Calvo Mackenna Hospital before and after the introduction of the pneumococcal vaccine into the National Immunization Program. Passive surveillance study. Patients<24 months with discharge diagnosis of bacterial pneumonia from Luis Calvo Mackenna Hospital were studied between 2009 and 2013. Data were obtained from the Luis Calvo Mackenna Hospital's Statistical Service. The incidence of pneumonia was evaluated in the pre-vaccination period (2009-2010) and in the post-vaccination period (2012-2013). During the study period, an average of 4,321 discharges/year was observed in children<24 months (range: 3,587-4,702), with a significant decrease from pre- to post-vaccination vaccine period (4,644 vs 4,013, P<.001). The average incidence of pneumonia ranged from 3.4/100,000 to 1.5/100,000 in the pre- and post-vaccine period, respectively (P=.009), with an annual mean of 157 cases of pneumonia in the pre- vaccine period, and 62 cases in the postvaccine period (P<.001) and a decrease in incidence between the two periods of 56%. This study confirms information previously obtained in other countries, which show a decrease in the incidence of pneumonia associated with the implementation of a pneumococcal vaccine at the population level. Ongoing surveillance is required to evaluate if this effect is maintained over time and expands to older populations. Copyright © 2015 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Monophosphoryl Lipid A Enhances Efficacy of a Francisella tularensis LVS-Catanionic Nanoparticle Subunit Vaccine against F. tularensis Schu S4 Challenge by Augmenting both Humoral and Cellular Immunity

PubMed Central

Richard, Katharina; Mann, Barbara J.; Qin, Aiping; Barry, Eileen M.; Ernst, Robert K.

2017-01-01

ABSTRACT Francisella tularensis, a bacterial biothreat agent, has no approved vaccine in the United States. Previously, we showed that incorporating lysates from partially attenuated F. tularensis LVS or fully virulent F. tularensis Schu S4 strains into catanionic surfactant vesicle (V) nanoparticles (LVS-V and Schu S4-V, respectively) protected fully against F. tularensis LVS intraperitoneal (i.p.) challenge in mice. However, we achieved only partial protection against F. tularensis Schu S4 intranasal (i.n.) challenge, even when employing heterologous prime-boost immunization strategies. We now extend these findings to show that both LVS-V and Schu S4-V immunization (i.p./i.p.) elicited similarly high titers of anti-F. tularensis IgG and that the titers could be further increased by adding monophosphoryl lipid A (MPL), a nontoxic Toll-like receptor 4 (TLR4) adjuvant that is included in several U.S. FDA-approved vaccines. LVS-V+MPL immune sera also detected more F. tularensis antigens than LVS-V immune sera and, after passive transfer to naive mice, significantly delayed the time to death against F. tularensis Schu S4 subcutaneous (s.c.) but not i.n. challenge. Active immunization with LVS-V+MPL (i.p./i.p.) also increased the frequency of gamma interferon (IFN-γ)-secreting activated helper T cells, IFN-γ production, and the ability of splenocytes to control intramacrophage F. tularensis LVS replication ex vivo. Active LVS-V+MPL immunization via heterologous routes (i.p./i.n.) significantly elevated IgA and IgG levels in bronchoalveolar lavage fluid and significantly enhanced protection against i.n. F. tularensis Schu S4 challenge (to ∼60%). These data represent a significant step in the development of a subunit vaccine against the highly virulent type A strains. PMID:28077440

Neuronal correlates of a virtual-reality-based passive sensory P300 network.

PubMed

Chen, Chun-Chuan; Syue, Kai-Syun; Li, Kai-Chiun; Yeh, Shih-Ching

2014-01-01

P300, a positive event-related potential (ERP) evoked at around 300 ms after stimulus, can be elicited using an active or passive oddball paradigm. Active P300 requires a person's intentional response, whereas passive P300 does not require an intentional response. Passive P300 has been used in incommunicative patients for consciousness detection and brain computer interface. Active and passive P300 differ in amplitude, but not in latency or scalp distribution. However, no study has addressed the mechanism underlying the production of passive P300. In particular, it remains unclear whether the passive P300 shares an identical active P300 generating network architecture when no response is required. This study aims to explore the hierarchical network of passive sensory P300 production using dynamic causal modelling (DCM) for ERP and a novel virtual reality (VR)-based passive oddball paradigm. Moreover, we investigated the causal relationship of this passive P300 network and the changes in connection strength to address the possible functional roles. A classical ERP analysis was performed to verify that the proposed VR-based game can reliably elicit passive P300. The DCM results suggested that the passive and active P300 share the same parietal-frontal neural network for attentional control and, underlying the passive network, the feed-forward modulation is stronger than the feed-back one. The functional role of this forward modulation may indicate the delivery of sensory information, automatic detection of differences, and stimulus-driven attentional processes involved in performing this passive task. To our best knowledge, this is the first study to address the passive P300 network. The results of this study may provide a reference for future clinical studies on addressing the network alternations under pathological states of incommunicative patients. However, caution is required when comparing patients' analytic results with this study. For example, the task presented here is not applicable to incommunicative patients.

Neuronal Correlates of a Virtual-Reality-Based Passive Sensory P300 Network

PubMed Central

Chen, Chun-Chuan; Syue, Kai-Syun; Li, Kai-Chiun; Yeh, Shih-Ching

2014-01-01

P300, a positive event-related potential (ERP) evoked at around 300 ms after stimulus, can be elicited using an active or passive oddball paradigm. Active P300 requires a person’s intentional response, whereas passive P300 does not require an intentional response. Passive P300 has been used in incommunicative patients for consciousness detection and brain computer interface. Active and passive P300 differ in amplitude, but not in latency or scalp distribution. However, no study has addressed the mechanism underlying the production of passive P300. In particular, it remains unclear whether the passive P300 shares an identical active P300 generating network architecture when no response is required. This study aims to explore the hierarchical network of passive sensory P300 production using dynamic causal modelling (DCM) for ERP and a novel virtual reality (VR)-based passive oddball paradigm. Moreover, we investigated the causal relationship of this passive P300 network and the changes in connection strength to address the possible functional roles. A classical ERP analysis was performed to verify that the proposed VR-based game can reliably elicit passive P300. The DCM results suggested that the passive and active P300 share the same parietal-frontal neural network for attentional control and, underlying the passive network, the feed-forward modulation is stronger than the feed-back one. The functional role of this forward modulation may indicate the delivery of sensory information, automatic detection of differences, and stimulus-driven attentional processes involved in performing this passive task. To our best knowledge, this is the first study to address the passive P300 network. The results of this study may provide a reference for future clinical studies on addressing the network alternations under pathological states of incommunicative patients. However, caution is required when comparing patients’ analytic results with this study. For example, the task presented here is not applicable to incommunicative patients. PMID:25401520

Maternal HIV-1 Env Vaccination for Systemic and Breast Milk Immunity To Prevent Oral SHIV Acquisition in Infant Macaques

PubMed Central

Eudailey, Joshua A.; Dennis, Maria L.; Parker, Morgan E.; Phillips, Bonnie L.; Huffman, Tori N.; Bay, Camden P.; Hudgens, Michael G.; Wiseman, Roger W.; Pollara, Justin J.; Fouda, Genevieve G.; Ferrari, Guido; Pickup, David J.; Kozlowski, Pamela A.; Van Rompay, Koen K. A.; De Paris, Kristina

2018-01-01

ABSTRACT Mother-to-child transmission (MTCT) of human immunodeficiency virus type 1 (HIV-1) contributes to an estimated 150,000 new infections annually. Maternal vaccination has proven safe and effective at mitigating the impact of other neonatal pathogens and is one avenue toward generating the potentially protective immune responses necessary to inhibit HIV-1 infection of infants through breastfeeding. In the present study, we tested the efficacy of a maternal vaccine regimen consisting of a modified vaccinia virus Ankara (MVA) 1086.C gp120 prime-combined intramuscular-intranasal gp120 boost administered during pregnancy and postpartum to confer passive protection on infant rhesus macaques against weekly oral exposure to subtype C simian-human immunodeficiency virus 1157ipd3N4 (SHIV1157ipd3N4) starting 6 weeks after birth. Despite eliciting a robust systemic envelope (Env)-specific IgG response, as well as durable milk IgA responses, the maternal vaccine did not have a discernible impact on infant oral SHIV acquisition. This study revealed considerable variation in vaccine-elicited IgG placental transfer and a swift decline of both Env-specific antibodies (Abs) and functional Ab responses in the infants prior to the first challenge, illustrating the importance of pregnancy immunization timing to elicit optimal systemic Ab levels at birth. Interestingly, the strongest correlation to the number of challenges required to infect the infants was the percentage of activated CD4+ T cells in the infant peripheral blood at the time of the first challenge. These findings suggest that, in addition to maternal immunization, interventions that limit the activation of target cells that contribute to susceptibility to oral HIV-1 acquisition independently of vaccination may be required to reduce infant HIV-1 acquisition via breastfeeding. IMPORTANCE Without novel strategies to prevent mother-to-child HIV-1 transmission, more than 5% of HIV-1-exposed infants will continue to acquire HIV-1, most through breastfeeding. This study of rhesus macaque dam-and-infant pairs is the first preclinical study to investigate the protective role of transplacentally transferred HIV-1 vaccine-elicited antibodies and HIV-1 vaccine-elicited breast milk antibody responses in infant oral virus acquisition. It revealed highly variable placental transfer of potentially protective antibodies and emphasized the importance of pregnancy immunization timing to reach peak antibody levels prior to delivery. While there was no discernible impact of maternal immunization on late infant oral virus acquisition, we observed a strong correlation between the percentage of activated CD4+ T cells in infant peripheral blood and a reduced number of challenges to infection. This finding highlights an important consideration for future studies evaluating alternative strategies to further reduce the vertical HIV-1 transmission risk. PMID:29359183

Observational study to investigate vertically acquired passive immunity in babies of mothers vaccinated against H1N1v during pregnancy.

PubMed

Puleston, R L; Bugg, G; Hoschler, K; Konje, J; Thornton, J; Stephenson, I; Myles, P; Enstone, J; Augustine, G; Davis, Y; Zambon, M; Nicholson, K G; Nguyen-Van-Tam, J S

2010-12-01

The primary objective was to determine the proportion of babies who acquired passive immunity to A/H1N1v, born to mothers who accepted vaccination as part of the national vaccination programme while pregnant (during the second and/or third trimesters) against the novel A/H1N1v influenza virus (exposed group) compared with unvaccinated (unexposed) mothers. An observational study at three sites in the UK. The purpose was to determine if mothers immunised against A/H1N1v during the pandemic vaccination period transferred that immunity to their child in utero. Three sites in the UK [Queen's Medical Centre, Nottingham; City Hospital, Nottingham (both forming University Hospitals Nottingham), and Leicester Royal Infirmary (part of University Hospitals Leicester)]. All pregnant women in the second and third trimester presenting at the NHS hospitals above to deliver were eligible to participate in the study. Women were included regardless of age, social class, ethnicity, gravida and parity status, past and current medical history (including current medications), ethnicity, mode of delivery and pregnancy outcome (live/stillbirth). At enrolment, participants provided written consent and completed a questionnaire. At parturition, venous cord blood was obtained for serological antibody analysis. Serological analysis was undertaken by the Respiratory Virus Unit (RVU), Health Protection Agency (HPA) Centre for Infections, London. The primary end point in the study was the serological results of the cord blood samples for immunity to A/H1N1v. Regarding a suitable threshold for the determination of a serological response consistent with clinical protection, this issue is somewhat complex for pandemic influenza. The European Medicines Agency (EMEA) Committee for Human Medicinal Products (CHMP) judges that a haemagglutination inhibition (HI) titre of 1 : 40 is an acceptable threshold. However, this level was set in the context of licensing plain trivalent seasonal vaccine, where a titre of 1 : 40 is but one of several related immunogenicity criteria, and supported by paired sera capable of demonstrating a fourfold rise in antibody titre in response to vaccination. The current study mainly investigated the effects of an AS03-adjuvanted monovalent vaccine, and it was not possible to obtain paired sera where the initial sample was taken before vaccination (in vaccinated subjects). Of possibly greater relevance is the fact that it has been established from the study of early outbreaks of pandemic influenza in secondary schools in the UK (HPA, unpublished observations) that an HI antibody titre of 1 : 32 seems to be the threshold for a humoral response to 'wild-type' A/H1N1v infection. On that basis, a threshold of 1 : 32 is at least as appropriate as one of 1 : 40, especially in unvaccinated individuals. Given the difficulties that would accrue by applying thresholds of 1 : 32 in unvaccinated patients and 1 : 40 in vaccinated patients, we have therefore applied a threshold of 1 : 32 and 1 : 40, to increase the robustness of our findings. Differences arising are described. A microneutralisation (MN) titre of 1 : 40 may be also used, although it is not part of the CHMP criteria for vaccine licensure. Nonetheless, we utilised this analysis as a secondary end point, based on a conservative threshold of 1 : 60. Reverse cumulative distribution percentage curves for haemagglutinin dilution and MN titres demonstrate background immunity in babies of unvaccinated mothers of 25%-30%. Humoral immunity in babies of vaccinated mothers was present in 80% of the group. The difference in positive immunity between the babies of unvaccinated and vaccinated mothers was statistically significant (chi-squared test, p < 0.001). Our findings reveal a highly significant difference in HI titres between babies born to mothers vaccinated with pandemic-specific vaccine against A/H1N1v during the 2009-10 pandemic period. The subjects recruited were comparable from a baseline perspective and thus do not represent different groups that otherwise could have introduced bias into the study. Continued circulation of 2009 A/H1N1-like viruses is uncertain, but is possible as seasonal influenza in years to come. It is possible that future seasonal waves may display increased virulence. Given the adverse outcomes experienced for a small proportion of pregnant women during the influenza pandemic of 2009-10, this study provides useful evidence to support vaccination in pregnancy to protect both the mother and baby. The National Institute for Health Research Health Technology Assessment programme.

Local infiltration of rabies immunoglobulins without systemic intramuscular administration: An alternative cost effective approach for passive immunization against rabies

PubMed Central

Bharti, Omesh Kumar; Madhusudana, Shampur Narayan; Gaunta, Pyare Lal; Belludi, Ashwin Yajaman

2016-01-01

ABSTRACT Presently the dose of rabies immunoglobulin (RIG) which is an integral part of rabies post exposure prophylaxis (PEP) is calculated based on body weight though the recommendation is to infiltrate the wound(s). This practice demands large quantities of RIG which may be unaffordable to many patients. In this background, we conducted this study to know if the quantity and cost of RIG can be reduced by restricting passive immunization to local infiltration alone and avoiding systemic intramuscular administration based on the available scientific evidence. Two hundred and sixty nine category III patients bitten by suspect or confirmed rabid dogs/animals were infiltrated with equine rabies immunoglobulin (ERIGs) in and around the wound. The quantity of ERIG used was proportionate to the size and number of wounds irrespective of their body weight. They were followed with a regular course of rabies vaccination by intra-dermal route. As against 363 vials of RIGs required for all these cases as per current recommendation based on body weight, they required only 42 vials of 5ml RIG. Minimum dose of RIGs given was 0.25 ml and maximum dose given was 8 ml. On an average 1.26 ml of RIGs was required per patient that costs Rs. 150 ($3). All the patients were followed for 9 months and they were healthy and normal at the end of observation period. With local infiltration, that required small quantities of RIG, the RIGs could be made available to all patients in times of short supply in the market. A total of 30 (11%) serum samples of patients were tested for rabies virus neutralizing antibodies by the rapid fluorescent focus inhibition test (RFFIT) and all showed antibody titers >0.5 IU/mL by day 14. In no case the dose was higher than that required based on body weight and no immunosuppression resulted. To conclude, this pilot study shows that local infiltration of RIG need to be considered in times of non-availability in the market or unaffordability by poor patients. This preliminary study needs to be done on larger scale in other centers with long term follow up to substantiate the results of our study. PMID:26317441

A Prospective Study of the Incidence of Myocarditis/Pericarditis and New Onset Cardiac Symptoms following Smallpox and Influenza Vaccination

PubMed Central

Engler, Renata J. M.; Nelson, Michael R.; Collins Jr., Limone C.; Spooner, Christina; Hemann, Brian A.; Gibbs, Barnett T.; Atwood, J. Edwin; Howard, Robin S.; Chang, Audrey S.; Cruser, Daniel L.; Gates, Daniel G.; Vernalis, Marina N.; Lengkeek, Marguerite S.; McClenathan, Bruce M.; Jaffe, Allan S.; Cooper, Leslie T.; Black, Steve; Carlson, Christopher; Wilson, Christopher; Davis, Robert L.

2015-01-01

Background Although myocarditis/pericarditis (MP) has been identified as an adverse event following smallpox vaccine (SPX), the prospective incidence of this reaction and new onset cardiac symptoms, including possible subclinical injury, has not been prospectively defined. Purpose The study’s primary objective was to determine the prospective incidence of new onset cardiac symptoms, clinical and possible subclinical MP in temporal association with immunization. Methods New onset cardiac symptoms, clinical MP and cardiac specific troponin T (cTnT) elevations following SPX (above individual baseline values) were measured in a multi-center prospective, active surveillance cohort study of healthy subjects receiving either smallpox vaccine or trivalent influenza vaccine (TIV). Results New onset chest pain, dyspnea, and/or palpitations occurred in 10.6% of SPX-vaccinees and 2.6% of TIV-vaccinees within 30 days of immunization (relative risk (RR) 4.0, 95% CI: 1.7-9.3). Among the 1081 SPX-vaccinees with complete follow-up, 4 Caucasian males were diagnosed with probable myocarditis and 1 female with suspected pericarditis. This indicates a post-SPX incidence rate more than 200-times higher than the pre-SPX background population surveillance rate of myocarditis/pericarditis (RR 214, 95% CI 65-558). Additionally, 31 SPX-vaccinees without specific cardiac symptoms were found to have over 2-fold increases in cTnT (>99th percentile) from baseline (pre-SPX) during the window of risk for clinical myocarditis/pericarditis and meeting a proposed case definition for possible subclinical myocarditis. This rate is 60-times higher than the incidence rate of overt clinical cases. No clinical or possible subclinical myocarditis cases were identified in the TIV-vaccinated group. Conclusions Passive surveillance significantly underestimates the true incidence of myocarditis/pericarditis after smallpox immunization. Evidence of subclinical transient cardiac muscle injury post-vaccinia immunization is a finding that requires further study to include long-term outcomes surveillance. Active safety surveillance is needed to identify adverse events that are not well understood or previously recognized. PMID:25793705

Layer-By-Layer Nanoparticle Vaccines Carrying the G Protein CX3C Motif Protect against RSV Infection and Disease.

PubMed

Jorquera, Patricia A; Oakley, Katie E; Powell, Thomas J; Palath, Naveen; Boyd, James G; Tripp, Ralph A

2015-10-12

Respiratory syncytial virus (RSV) is the single most important cause of serious lower respiratory tract infections in young children; however no effective treatment or vaccine is currently available. Previous studies have shown that therapeutic treatment with a monoclonal antibody (clone 131-2G) specific to the RSV G glycoprotein CX3C motif, mediates virus clearance and decreases leukocyte trafficking to the lungs of RSV-infected mice. In this study, we show that vaccination with layer-by-layer nanoparticles (LbL-NP) carrying the G protein CX3C motif induces blocking antibodies that prevent the interaction of the RSV G protein with the fractalkine receptor (CX3CR1) and protect mice against RSV replication and disease pathogenesis. Peptides with mutations in the CX3C motif induced antibodies with diminished capacity to block G protein-CX3CR1 binding. Passive transfer of these anti-G protein antibodies to mice infected with RSV improved virus clearance and decreased immune cell trafficking to the lungs. These data suggest that vaccination with LbL-NP loaded with the CX3C motif of the RSV G protein can prevent manifestations of RSV disease by preventing the interaction between the G protein and CX3CR1 and recruitment of immune cells to the airways.

Cytokines, chemokines, and colony-stimulating factors in human milk: the 1997 update.

PubMed

Garofalo, R P; Goldman, A S

1998-01-01

Epidemiologic studies conducted over the past 30 years to investigate the protective functions of human milk strongly support the notion that breast-feeding prevents infantile infections, particularly those affecting the gastrointestinal and respiratory tracts. However, more recent clinical and experimental observations also suggest that human milk not only provides passive protection, but also can directly modulate the immunological development of the recipient infant. The study of this remarkable defense system in human milk has been difficult due to its biochemical complexity, the small concentration of certain bioactive components, the compartmentalization of some of these agents, the dynamic quantitative and qualitative changes of milk during lactation, and the lack of specific reagents to quantify these agents. Nevertheless, a host of bioactive substances including hormones, growth factors, and immunological factors such as cytokines have been identified in human milk. Cytokines are pluripotent polypeptides that act in autocrine/paracrine fashions by binding to specific cellular receptors. They operate in networks and orchestrate the development and functions of the immune system. Several different cytokines and chemokines have been discovered in human milk over the past years, and the list is growing very rapidly. This article will review the current knowledge about the increasingly complex network of chemoattractants, activators, and anti-inflammatory cytokines present in human milk and their potential role in compensating for the developmental delay of the neonate immune system.

Cytokines in human milk.

PubMed

Garofalo, Roberto

2010-02-01

Epidemiologic studies conducted in the past 30 years to investigate the protective functions of human milk strongly support the notion that breastfeeding prevents infantile infections, particularly those affecting the gastrointestinal and respiratory tracts. However, more recent clinical and experimental observations also suggest that human milk not only provides passive protection, but also can directly modulate the immunological development of the recipient infant. The study of this remarkable defense system in human milk has been difficult because of its biochemical complexity, the small concentration of certain bioactive components, the compartmentalization of some of these agents, the dynamic quantitative and qualitative changes of milk during lactation, and the lack of specific reagents to quantify these agents. However, a host of bioactive substances, including hormones, growth factors, and immunological factors such as cytokines, have been identified in human milk. Cytokines are pluripotent polypeptides that act in autocrine/paracrine fashions by binding to specific cellular receptors. They operate in networks and orchestrate the development and functions of immune system. Several different cytokines and chemokines have been discovered in human milk in the past years, and the list is growing very rapidly. This article will review the current knowledge about the increasingly complex network of chemoattractants, activators, and anti-inflammatory cytokines present in human milk and their potential role in compensating for the developmental delay of the neonate immune system. Copyright 2010. Published by Mosby, Inc.

Trends in recombinant protein use in animal production.

PubMed

Gifre, Laia; Arís, Anna; Bach, Àlex; Garcia-Fruitós, Elena

2017-03-04

Recombinant technologies have made possible the production of a broad catalogue of proteins of interest, including those used for animal production. The most widely studied proteins for the animal sector are those with an important role in reproduction, feed efficiency, and health. Nowadays, mammalian cells and fungi are the preferred choice for recombinant production of hormones for reproductive purposes and fibrolytic enzymes to enhance animal performance, respectively. However, the development of low-cost products is a priority, particularly in livestock. The study of cell factories such as yeast and bacteria has notably increased in the last decades to make the new developed reproductive hormones and fibrolytic enzymes a real alternative to the marketed ones. Important efforts have also been invested to developing new recombinant strategies for prevention and therapy, including passive immunization and modulation of the immune system. This offers the possibility to reduce the use of antibiotics by controlling physiological processes and improve the efficacy of preventing infections. Thus, nowadays different recombinant fibrolytic enzymes, hormones, and therapeutic molecules with optimized properties have been successfully produced through cost-effective processes using microbial cell factories. However, despite the important achievements for reducing protein production expenses, alternative strategies to further reduce these costs are still required. In this context, it is necessary to make a giant leap towards the use of novel strategies, such as nanotechnology, that combined with recombinant technology would make recombinant molecules affordable for animal industry.

Latency of Herpes Simplex Virus in Absence of Neutralizing Antibody: Model for Reactivation

NASA Astrophysics Data System (ADS)

Sekizawa, Tsuyoshi; Openshaw, Harry; Wohlenberg, Charles; Notkins, Abner Louis

1980-11-01

Mice inoculated with herpes simplex virus (type 1) by the lip or corneal route and then passively immunized with rabbit antibody to herpes simplex virus developed a latent infection in the trigeminal ganglia within 96 hours. Neutralizing antibody to herpes simplex virus was cleared from the circulation and could not be detected in most of these mice after 2 months. Examination of ganglia from the antibody-negative mice revealed latent virus in over 90 percent of the animals, indicating that serum neutralizing antibody is not necessary to maintain the latent state. When the lips or corneas of these mice were traumatized, viral reactivation occurred in up to 90 percent of the mice, as demonstrated by the appearance of neutralizing antibody. This study provides a model for identifying factors that trigger viral reactivation.

The type IV pilin of Burkholderia mallei is highly immunogenic but fails to protect against lethal aerosol challenge in a murine model.

PubMed

Fernandes, Paula J; Guo, Qin; Waag, David M; Donnenberg, Michael S

2007-06-01

Burkholderia mallei is the cause of glanders and a proven biological weapon. We identified and purified the type IV pilin protein of this organism to study its potential as a subunit vaccine. We found that purified pilin was highly immunogenic. Furthermore, mice infected via sublethal aerosol challenge developed significant increases in titers of antibody against the pilin, suggesting that it is expressed in vivo. Nevertheless, we found no evidence that high-titer antipilin antisera provided passive protection against a sublethal or lethal aerosol challenge and no evidence of protection afforded by active immunization with purified pilin. These results contrast with the utility of type IV pilin subunit vaccines against other infectious diseases and highlight the need for further efforts to identify protective responses against this pathogen.

Glucose-6-phosphate isomerase is necessary for embryo implantation in the domestic ferret

PubMed Central

Schulz, Laura Clamon; Bahr, Janice M.

2003-01-01

The mechanism of implantation in carnivores is poorly understood. However, a previously unidentified 60-kDa protein has been shown to be necessary for embryo implantation in ferrets. Here we identify this protein as glucose-6-phosphate isomerase (GPI). GPI is expressed by the corpus luteum on days 6–9 of pregnancy, the time at which implantation-promoting activity has been found in corpora lutea. Passive immunization against GPI reduced the number of implantation sites in pregnant ferrets in a dose-dependent manner. GPI is a multifunctional protein. Although first identified for its role in glycolysis, GPI has since been implicated in neural growth, lymphocyte maturation, and metastasis. This study demonstrates a previously uncharacterized function of this protein that may represent the natural motility-stimulating activity that has been co-opted by tumor cells. PMID:12826606

Maternal transfer of RSV immunity in cotton rats vaccinated during pregnancy.

PubMed

Blanco, Jorge C G; Pletneva, Lioubov M; Oue, Raymonde O; Patel, Mira C; Boukhvalova, Marina S

2015-10-05

Respiratory Syncytial Virus (RSV) is the leading cause of pneumonia and bronchiolitis in infants, resulting in significant morbidity and mortality worldwide. There is currently no RSV vaccine. Although maternal serum antibodies against RSV are efficiently transferred through placenta protecting human infants from RSV-induced disease, this protection is short-lived and the methods for extending and augmenting protection are not known. The objective of this study was to develop an animal model of maternal RSV vaccination using the Sigmodon hispidus cotton rat. Naïve or RSV-primed female cotton rats were inoculated with live RSV and set in breeding pairs. Antibody transfer to the litters was quantified and the offspring were challenged with RSV at different ages for analysis of protection against viral replication and lung inflammation. There was a strong correlation between RSV-neutralizing antibody (NA) titers in cotton rat mothers and their pups, which also correlated with protection of litters against virus challenge. Passive protection was short-lived and strongly reduced in animals at 4 weeks after birth. Protection of litters was significantly enhanced by inoculating mothers parenterally with live RSV and inversely correlated with the expression of lung cytokines and pathology. Importantly, vaccination and boosting of naïve mothers with the live RSV produced the highest levels of NAs. We conclude that maternal vaccination against RSV in the cotton rat can be used to define vaccine preparations that could improve preexistent immunity and induce subsequent transfer of efficient immunity to infants. Copyright © 2015 Elsevier Ltd. All rights reserved.

Neuroendocrine immunomodulation network dysfunction in SAMP8 mice and PrP-hAβPPswe/PS1ΔE9 mice: potential mechanism underlying cognitive impairment

PubMed Central

Wang, Jian-hui; Cheng, Xiao-rui; Zhang, Xiao-rui; Wang, Tong-xing; Xu, Wen-jian; Li, Fei; Liu, Feng; Cheng, Jun-ping; Bo, Xiao-chen; Wang, Sheng-qi; Zhou, Wen-xia; Zhang, Yong-xiang

2016-01-01

Senescence-accelerated mouse prone 8 strain (SAMP8) and PrP-hAβPPswe/PS1ΔE9 (APP/PS1) mice are classic animal models of sporadic Alzheimer's disease and familial AD respectively. Our study showed that object recognition memory, spatial learning and memory, active and passive avoidance were deteriorated and neuroendocrine immunomodulation (NIM) network was imbalance in SAMP8 and APP/PS1 mice. SAMP8 and APP/PS1 mice had their own specific phenotype of cognition, neuroendocrine, immune and NIM molecular network. The endocrine hormone corticosterone, luteinizing hormone and follicle-stimulating hormone, chemotactic factor monocyte chemotactic protein-1, macrophage inflammatory protein-1β, regulated upon activation normal T cell expressed and secreted factor and eotaxin, pro-inflammatory factor interleukin-23, and the Th1 cell acting as cell immunity accounted for cognitive deficiencies in SAMP8 mice, while adrenocorticotropic hormone and gonadotropin-releasing hormone, colony stimulating factor granulocyte colony stimulating factor, and Th2 cell acting as humoral immunity in APP/PS1 mice. On the pathway level, chemokine signaling and T cell receptor signaling pathway played the key role in cognition impairments of two models, while cytokine-cytokine receptor interaction and natural killer cell mediated cytotoxicity were more important in cognitive deterioration of SAMP8 mice than APP/PS1 mice. This mechanisms of NIM network underlying cognitive impairment is significant for further understanding the pathogenesis of AD and can provide useful information for development of AD therapeutic drug. PMID:27049828

Management of chickenpox with frozen mother's milk.

PubMed

Verd, Sergio; López, Esther

2012-08-01

If a mother has contracted chickenpox, the antibodies in her milk confer immunity against chickenpox to her breastfed babies. This passive immunization may avoid or spare the breastfed babies' symptoms of chickenpox. It is hypothesized that frozen breast milk may shorten chickenpox duration because specific antibodies against varicella zoster have been detected in human milk and they are resistant to digestion and are stable in frozen milk. The clinical outcomes of chickenpox in a 9-year-old boy and his father on frozen breast milk are reported. The study comprised a varicella-vaccine-refusing family attending a private office of pediatrics. The boy presented with a crusted varicella rash. The medical history revealed premature cessation of the typical varicella rash on day 3. It was coincidental with a supply of frozen human milk by his mother. Next, the father (41 years old) of this patient contracted chickenpox: he was on frozen breast milk from day 2, and no new pox emerged thereafter. The rash spread and numbered 50 to 150 lesions on day 2. Instead, the typical rash was expected to appear in three successive crops of lesions throughout the first week. The disease usually numbers approximately 250-500 lesions in unvaccinated healthy persons. Frozen breast milk may shorten chickenpox duration.

Study on development of Vipera lebetina snake anti-venom in chicken egg yolk for passive immunization

PubMed Central

Zolfagharian, Hossein; Dounighi, Naser Mohammadpour

2015-01-01

Chicken egg yolk antibodies against Vipera lebetina venom were evaluated for their antivenom potential. White leghorn hens were immunized with detoxified V. lebetina venom (γ-irradiated venom). The detoxified venom (200 μg) was mixed with an equal volume of complete Freund's adjuvant and was injected intramuscularly into the hens. The antibodies showed high activity (1.6 LD50/mL) in egg yolks after 12 d of venom injection. The eggs were collected after 12 days, and the egg yolks were removed and washed with purified water to remove any contamination with egg whites. The purification was performed using a method described by Maya Devi et al., followed by gel filtration (Sephadex G-50). The purity and molecular weight of antivenom antibodies (IgY) were determined using electrophoresis, and the molecular weight was found to be approximately 185 kDa. The potency of IgY was 6 LD50/mL (mice), i.e., 1 mL of IgY could neutralize 43.8 μg of standard V. lebetina venom). Our results showed that chicken egg yolk antibodies were effective in neutralizing the lethality and several pharmacological effects of V. lebetina venom and could be used for developing effective antivenom. PMID:25700656

Control strategies against Campylobacter at the poultry production level: biosecurity measures, feed additives and vaccination.

PubMed

Meunier, M; Guyard-Nicodème, M; Dory, D; Chemaly, M

2016-05-01

Campylobacteriosis is the most prevalent bacterial foodborne gastroenteritis affecting humans in the European Union, and ranks second in the United States only behind salmonellosis. In Europe, there are about nine million cases of campylobacteriosis every year, making the disease a major public health issue. Human cases are mainly caused by the zoonotic pathogen Campylobacter jejuni. The main source of contamination is handling or consumption of poultry meat. Poultry constitutes the main reservoir of Campylobacter, substantial quantities of which are found in the intestines following rapid, intense colonization. Reducing Campylobacter levels in the poultry chain would decrease the incidence of human campylobacteriosis. As primary production is a crucial step in Campylobacter poultry contamination, controlling the infection at this level could impact the following links along the food chain (slaughter, retail and consumption). This review describes the control strategies implemented during the past few decades in primary poultry production, including the most recent studies. In fact, the implementation of biosecurity and hygiene measures is described, as well as the immune strategy with passive immunization and vaccination trials and the nutritional strategy with the administration of organic and fatty acids, essential oil and plant-derived compound, probiotics, bacteriocins and bacteriophages. © 2015 The Society for Applied Microbiology.

Interleukin 6 production in experimental cerebral malaria: modulation by anticytokine antibodies and possible role in hypergammaglobulinemia

PubMed Central

1990-01-01

The production of Interleukin 6 (IL-6) was studied during experimental cerebral malaria (ECM) induced by Plasmodium berghei ANKA (PbA) infection. IL-6 is present in the serum of mice with ECM, the highest concentrations being observed in mice with full-blown neurological syndrome. High IL-6 levels were also observed, however, in the absence of pathology in nonlethal malaria infection. These data suggest that IL- 6 is produced in large amounts during malaria infection, but does not play a major role in the pathogenesis of ECM. A modulation of IL-6 production in ECM was achieved by in vivo treatment with other anticytokine antibodies: antibodies to interferon (IFN-gamma) or to tumor necrosis factor (TNF) abolished the rise of IL-6, while anti-IL-3 and anti-granulocyte/macrophage colony-stimulating factor antibodies only partially prevented this rise, suggesting that the two cytokines IFN-gamma and TNF are important intermediates in IL-6 production. Passive immunization against IL-6 did not prevent ECM, but significantly reduced serum IgG levels in malaria-infected mice. Thus, by its effects on B cells, IL-6 may be involved in hypergammaglobulinemia and immune-complex diseases, e.g., glomerulonephritis observed during malaria infection. PMID:2121890

Development and characterization of monoclonal antibodies against canine PD-1 and PD-L1.

PubMed

Nemoto, Yuki; Shosu, Kazuha; Okuda, Masaru; Noguchi, Shunsuke; Mizuno, Takuya

2018-04-01

Recent research has focused on immunotherapy, particularly with regard to cancer treatment. Programmed death-1 and programmed death ligand 1 (PD-1/PD-L1) pathway blockade is a central topic of the promising immunotherapy field. In veterinary medicine, observations of the PD-1/PD-L1 pathway, including the relationship between immune cells and diseases, have increased. In this study, monoclonal antibodies specific to canine PD-1 and PD-L1 were developed, and the antibodies against PD-1 and PD-L1 bind to PD-1 and PD-L1 overexpressing cells, respectively. Additionally, each antibody interfered with the interaction between PD-1 and PD-L1. The expression of PD-1 and PD-L1 was detected on activated T cells from canine peripheral blood mononuclear cells (PBMC), and, remarkably, was the first recorded instance of PD-L1 expression on canine immature dendritic cells. Production of IFN-γ by activated T cells increased significantly when incubated with anti-PD-1 antibody alone and with both anti-PD-1 and anti-PD-L1 antibodies, revealing the functional effects of the antibodies. The antibodies will be useful for research on immune systems and may be the first passive immunotherapy approach in canine cancer patients. Copyright © 2018 Elsevier B.V. All rights reserved.

Comparative evaluation of cell culture-adapted and chicken embryo-adapted fowl pox vaccine strains.

PubMed

Baxi, M K; Oberoi, M S

1999-01-01

Two types of vaccines, chicken embryo adapted (VacCE) and cell culture adapted (VacCC), were tested for their efficacy to elicite the immune response in birds vaccinated at 2 and 8 wk of age. The cell-mediated immune response studied by blastogenesis assay showed that birds vaccinated at the second week of age by both VacCE and VacCC vaccines had significant increase in T-lymphocyte count at 21 days postvaccination (PV) and 7 days postchallenge (PC), whereas in birds vaccinated at 8 wk of age, a significant increase was seen at 21 days PV and 7 days PC with the VacCC vaccine. The rise in passive hemagglutination titers was observed up to 21 days PV and 7 days PC in birds vaccinated at 2 wk of age. However, only the birds vaccinated with VacCC at 8 wk of age showed rise in titers at days 21 PV and 7 PC. Birds were challenged 90 days PV by scarification on the thigh region, and the birds vaccinated with VacCC showed 90% and 70% protection when vaccinated at 2 and 8 wk, respectively. The birds vaccinated with VacCE showed only 60% and 20% protection at the corresponding levels, respectively.

The evaluation of a positive direct antiglobulin test (autocontrol) in pretransfusion testing revisited.

PubMed

Judd, W J; Barnes, B A; Steiner, E A; Oberman, H A; Averill, D B; Butch, S H

1986-01-01

Direct antiglobulin tests (DATs) using anti-IgG were performed on 65,049 blood samples from prospective transfusion recipients; 3570 tests (5.49%) were positive. Using criteria published previously (primarily excluding patients not transfused within the preceding 14 days), 778 samples from other than neonatal patients were selected for further evaluation. Eluates that did not react were obtained on 518 (66.6%) of these samples. Warm-reactive autoantibodies were apparent in 192 eluates, while 16 contained drug-related antibodies, anti-A or anti-B from prior transfusion with ABO mismatched blood components, or anti-D passively acquired from immune serum globulin. Fifty-two eluates contained alloantibodies; however, in only six of these cases did the corresponding serum lack unexpected alloantibodies, as determined by routine pretransfusion studies. Three additional weakly reactive clinically significant alloantibodies were detected solely through additional serum tests performed on DAT-positive samples. On the basis of these findings, the DAT had a low predictive value when used to detect the early manifestations of an immune response to recently transfused red cells. Elimination of the autocontrol from routine pretransfusion testing, therefore, carries minimal risk to patients yet will undoubtedly contribute to the containment of health care costs. Moreover, the risk is lower than that associated with the elimination of the antiglobulin crossmatch.

Hypogammaglobulinaemia in nephrotic rats is attributable to hypercatabolism of IgG.

PubMed Central

Beaman, M; Oldfield, S; MacLennan, I C; Michael, J; Adu, D

1988-01-01

The effect of the nephrotic syndrome induced by puromycin aminonucleoside (PA) in rats on specific antibody responses to 2,4 dinitrophenyl (DNP) conjugated to either spider crab haemocyanin (MSH), a T cell-dependent antigen, or hydroxyethyl starch (HES), a T cell-independent type 2 antigen were studied. The serum IgG anti-DNP levels following immunization with both antigens were reduced in nephrotic animals compared with controls while IgM anti-DNP antibody titres were higher. The half-life of IgG anti-DNP antibodies passively transferred into non-immunized nephrotic rats was markedly reduced while the half-life of anti-DNP antibodies of the IgM class was comparable to that in controls. Low serum IgG and elevated IgM levels were seen in nephrotic animals compared to controls. Antibody-forming cells specific for DNP were demonstrated by immunohistology on rat spleens and the numbers of both IgG and IgM-producing cells were found to be significantly increased (P less than 0.05) in nephrotic animals in response to both DNP-HES and DNP-MSH. These data indicate that in nephrotic rats the alteration seen in the serum immunoglobulin levels is not attributable to reduced antibody production but increased catabolism of serum IgG antibodies. PMID:3233791

A Phase 2 randomized, observer-blind, placebo-controlled, dose-ranging trial of aluminum-adjuvanted respiratory syncytial virus F particle vaccine formulations in healthy women of childbearing age.

PubMed

August, Allison; Glenn, Gregory M; Kpamegan, Eloi; Hickman, Somia P; Jani, Dewal; Lu, Hanxin; Thomas, D Nigel; Wen, Judy; Piedra, Pedro A; Fries, Louis F

2017-06-27

Respiratory syncytial virus (RSV) causes significant morbidity and mortality in infants. We are developing an RSV fusion (F) protein nanoparticle vaccine for immunization of third trimester pregnant women to passively protect infants through transfer of RSV-specific maternal antibodies. The present trial was performed to assess the immunogenicity and safety of several formulations of RSV F vaccine in 1-dose or 2-dose schedules. Placebo, or vaccine with 60μg or 120μg RSV F protein and 0.2, 0.4, or 0.8mg aluminum, were administered intramuscularly on Days 0 and 28 to healthy women 18-35years old. Immunogenicity was assessed from Days 0 through 91 based on anti-F IgG and palivizumab-competitive antibody (PCA) by ELISA, and RSV A and B neutralizing antibodies by microneutralization (MN) assay. Solicited adverse events were collected through Day 7 and unsolicited adverse events through Day 91. All formulations were well-tolerated, with no treatment-related serious adverse events. Anti-F IgG and PCA responses were correlated and increased after both doses, while MN increased significantly only after the first dose, then plateaued. The timeliest and most robust antibody responses followed one dose of 120μg RSV F protein and 0.4mg aluminum, but persistence through 91days was modestly (∼25%) superior following two doses of 60μg RSV F protein and 0.8mg aluminum. Western blot analysis showed RSV infections in active vaccinees were reduced by 52% overall (p=0.009 overall) over the Day 0 through 90 period. RSV F nanoparticle vaccine formulations were well tolerated and immunogenic. The optimal combination of convenience and rapid response for immunization in the third trimester occurred with 120μg RSV F and 0.4mg aluminum, which achieved peak immune responses in 14days and sufficient persistence through 91days to allow for passive transfer of IgG antibodies to the fetus. NCT01960686. Copyright © 2017 Novavax. Published by Elsevier Ltd.. All rights reserved.

A rapid radioimmunoassay using /sup 125/I-labeled staphylococcal protein A for antibody to varicella-zoster virus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Richman, D.D.; Cleveland, P.H.; Oxman, M.N.

1981-05-01

A sensitive radioimmunoassay for serum antibody to varicella-zoster virus is described; it uses 125I-labeled staphylococcal protein A and a specially designed immunofiltration apparatus. The assay accurately distinguishes between individuals who are susceptible and those who are immune to infection with varicella-zoster virus. In addition, it can detect passive antibody in recipients of varicella-zoster immune globulin. This radioimmunoassay also detects the heterologous antibody responses that occasionally occur in patients infected with herpes simplex virus, which also have been detected by other antibody assays. The particular advantages of this assay are the use of noninfectious reagents, the speed of execution (less thanmore » 3 hr), the requirement for only small quantities of serum (30 microliters), the objectivity of end-point determination, and the capability of screening large numbers of sera. Consequently, this radioimmunoassay is especially useful for the rapid identification of susceptible individuals, which is essential for the appropriate management of patients and hospital personnel after exposure to varicella.« less

[Adults with chickenpox in the tropics].

PubMed

Hanssen, Jaap L J; Schakel, G J Joris; Fontilus-Rohoman, Jeanette M; Eeftinck Schattenkerk, Jsn Karel M

2015-01-01

In our hospital in the Dutch Caribbean, it is not uncommon for adults to be admitted for chickenpox infection. In contrast to the situation in temperate climates, not all adults are infected during childhood. Therefore, hospital staff are tested when first employed; of those aged between 20-29 years, 40% do not have antibodies against the varicella-zoster virus (VZV). We describe three cases of adults, aged 37, 51 and 90 years respectively, who presented with chickenpox. Compared to children, the clinical course in adults is more severe with the potential risk of life-threatening complications. In pregnancy or concomitant T cell immune deficiency, risk of a fulminant course is even higher. Treatment with aciclovir or valaciclovir is effective and associated with few side-effects. Passive immunization with VZV-immunoglobulin is indicated within 96 hours of exposure, typically followed by acyclovir or valaciclovir. As migration occurs from low endemic tropical areas to high endemic temperate areas, we should be aware of the risk of adult chickenpox in these migrants.

Desert Storm syndrome: sick soldiers and dead children?

PubMed

Doucet, I

1994-01-01

Ill-health has been reported by many soldiers and others deployed in the Persian Gulf during the Gulf War of 1991. Iraqi children have also been reported as suffering from an undiagnosed wasting disease. Little conclusive information has come to light; this paper reviews what is known at present, largely from anecdotal reports. Symptoms reported differ from post-traumatic stress syndrome as reported after previous conflicts; some are suggestive of a direct effect on the immune system. Various possible causes are examined, including post-traumatic stress disorder, infection, prophylactic medication, exposure to chemical and biological warfare agents, exposures resulting from oil spills and fires, and exposure to depleted uranium ammunition. The latter was used extensively for the first time in the Gulf War, and is manufactured and test-fired in Britain. The passive role of the British government in following up such reports is noted, in contrast with the more active official responses in the United States. It is suggested that Desert Storm Syndrome is one example of multiple assault upon the body's immune system.

Hepatitis A, B and nAnB: The Viruses and their Prevention

PubMed Central

Minuk, G. Y.

1985-01-01

Three viruses commonly infect the liver: hepatitis A virus (HAV), hepatitis B virus (HBV) and the virus(es) responsible for non A non B hepatitis (nAnB). HAV infection occurs predominantly by the fecal-oral route and thus is more common in areas where living conditions are poor and personal hygiene suboptimal. Immune serum globulin (ISG) prevents this form of hepatitis. HBV infection can be spread by either parenteral (e.g. drug abuse) or non-parenteral (e.g. intimate contact) routes. High risk, susceptible individuals should be vaccinated with the HBV vaccine for longterm protection. Hepatitis B immune globulin (HBIG) remains the treatment of choice after exposure, but its protective effect does not exceed three to four months. The nAnB agent is spread by the same routes as HBV infection. At present there is no convincing evidence that any form of active or passive prophylaxis is beneficial for this form of hepatitis. PMID:21279152

Post-transplantation Development of Food Allergies.

PubMed

Newman, Erik N; Firszt, Rafael

2018-01-29

The development of food allergies is increasingly being recognized as a post-solid organ transplant complication. In this article, we review the spectrum of post-transplant food allergy development and the proposed mechanisms for de novo food allergies and the clinical significance they pose. The development of new food allergies is disproportionately associated with pediatric liver transplants, where it occurs in up to 38% of select populations. The mechanism of food allergy development is not completely understood; however, it is likely promoted by unbalanced immune suppression. De novo food allergy development is a common complication of solid organ transplants with the highest risk occurring in pediatric liver transplant recipients. There are likely multiple mechanisms for food allergy development including passive transfer of membrane-bound IgE and lymphocytes from donor to recipient, as well as loss of food tolerance and active development of new food allergies. The optimal management of food allergies following organ transplants has not been well researched but may include changing the immune suppression regimen if the food allergy does not resolve without intervention.

Progress in HIV vaccine development

PubMed Central

Hsu, Denise C.; O'Connell, Robert J.

2017-01-01

ABSTRACT An HIV-1 vaccine is needed to curtail the HIV epidemic. Only one (RV144) out of the 6 HIV-1 vaccine efficacy trials performed showed efficacy. A potential mechanism of protection is the induction of functional antibodies to V1V2 region of HIV envelope. The 2 main current approaches to the generation of protective immunity are through broadly neutralizing antibodies (bnAb) and induction of functional antibodies (non-neutralizing Abs with other potential anti-viral functions). Passive immunization using bnAb has advanced into phase II clinical trials. The induction of bnAb using mimics of the natural Env trimer or B-cell lineage vaccine design is still in pre-clinical phase. An attempt at optimization of protective functional antibodies will be assessed next with the efficacy trial (HVTN702) about to start. With on-going optimization of prime/boost strategies, the development of mosaic immunogens, replication competent vectors, and emergence of new strategies designed to induce bnAb, the prospects for a preventive HIV vaccine have never been more promising. PMID:28281871

Monoclonal antibody form and function: manufacturing the right antibodies for treating drug abuse.

PubMed

Peterson, Eric; Owens, S Michael; Henry, Ralph L

2006-05-26

Drug abuse continues to be a major national and worldwide problem, and effective treatment strategies are badly needed. Antibodies are promising therapies for the treatment of medical problems caused by drug abuse, with several candidates in preclinical and early clinical trials. Monoclonal antibodies can be designed that have customized affinity and specificity against drugs of abuse, and because antibodies can be designed in various forms, in vivo pharmacokinetic characteristics can be tailored to suit specific clinical applications (eg, long-acting for relapse prevention, or short-acting for overdose). Passive immunization with antibodies against drugs of abuse has several advantages over active immunization, but because large doses of monoclonal antibodies may be needed for each patient, efficient antibody production technology is essential. In this minireview we discuss some of the antibody forms that may be effective clinical treatments for drug abuse, as well as several current and emerging production systems that could bridge the gap from discovery to patient use.

Maternal antibody transfer can lead to suppression of humoral immunity in developing zebra finches (Taeniopygia guttata).

PubMed

Merrill, Loren; Grindstaff, Jennifer L

2014-01-01

Maternally transferred antibodies have been documented in a wide range of taxa and are thought to adaptively provide protection against parasites and pathogens while the offspring immune system is developing. In most birds, transfer occurs when females deposit immunoglobulin Y into the egg yolk, and it is proportional to the amount in the female's plasma. Maternal antibodies can provide short-term passive protection as well as specific and nonspecific immunological priming, but high levels of maternal antibody can result in suppression of the offspring's humoral immune response. We injected adult female zebra finches (Taeniopygia guttata) with one of two antigens (lipopolysaccharide [LPS] or keyhole limpet hemocyanin [KLH]) or a control and then injected offspring with LPS, KLH, or a control on days 5 and 28 posthatch to examine the impact of maternally transferred antibodies on the ontogeny of the offspring's humoral immune system. We found that offspring of females exposed to KLH had elevated levels of KLH-reactive antibody over the first 17-28 days posthatch but reduced KLH-specific antibody production between days 28 and 36. We also found that offspring exposed to either LPS or KLH exhibited reduced total antibody levels, compared to offspring that received a control injection. These results indicate that high levels of maternal antibodies or antigen exposure during development can have negative repercussions on short-term antibody production and may have long-term fitness repercussions for the offspring.

Maternal Antibody Transfer Can Lead to Suppression of Humoral Immunity in Developing Zebra Finches (Taeniopygia guttata)

PubMed Central

Merrill, Loren; Grindstaff, Jennifer L.

2015-01-01

Maternally transferred antibodies have been documented in a wide range of taxa and are thought to adaptively provide protection against parasites and pathogens while the offspring immune system is developing. In most birds, transfer occurs when females deposit immunoglobulin Y into the egg yolk, and it is proportional to the amount in the female’s plasma. Maternal antibodies can provide short-term passive protection as well as specific and nonspecific immunological priming, but high levels of maternal antibody can result in suppression of the offspring’s humoral immune response. We injected adult female zebra finches (Taeniopygia guttata) with one of two antigens (lipo-polysaccharide [LPS] or keyhole limpet hemocyanin [KLH]) or a control and then injected offspring with LPS, KLH, or a control on days 5 and 28 posthatch to examine the impact of maternally transferred antibodies on the ontogeny of the offspring’s humoral immune system. We found that offspring of females exposed to KLH had elevated levels of KLH-reactive antibody over the first 17–28 days posthatch but reduced KLH-specific antibody production between days 28 and 36. We also found that offspring exposed to either LPS or KLH exhibited reduced total antibody levels, compared to offspring that received a control injection. These results indicate that high levels of maternal antibodies or antigen exposure during development can have negative repercussions on short-term antibody production and may have long-term fitness repercussions for the offspring. PMID:25244385

Genetic and antigenic characteristics of ApxIIA and ApxIIIA from Actinobacillus pleuropneumoniae serovars 2, 3, 4, 6, 8 and 15.

PubMed

To, Ho; Nagai, Shinya; Iwata, Akira; Koyama, Tomohiro; Oshima, Atsushi; Tsutsumi, Nobuyuki

2016-07-01

Apx toxins produced by Actinobacillus pleuropneumoniae are essential components of new generation vaccines. In this study, apxIIA and apxIIIA genes of serovars 2, 3, 4, 6, 8 and 15 were cloned and sequenced. Amino acid sequences of ApxIIA proteins of serovars 2, 3, 4, 6, 8 and 15 were almost identical to those of serovars 1, 5, 7, 9 and 11-13. Immunoblot analysis showed that rApxIIA from serovars 2 and 15 reacts strongly with sera from animals infected with various serovars. Sequence analysis revealed that ApxIIIA proteins has two variants, one in strains of serovar 2 and the other in strains of serovars 3, 4, 6, 8 and 15. A mouse cross-protection study showed that mice actively immunized with rApxIIIA/2 or rApxIIIA/15 are protected against challenge with A. pleuropneumoniae strains of serovars 3, 4, 6, 8, 15, and 2 expressing ApxIII/15 and ApxIII/2, respectively. Similarly, mice passively immunized with rabbit anti-rApxIIIA/2 or anti-rApxIIIA/15 sera were found to be protected against challenge with strains of serovars 2 and 15. Our study revealed antigenic and sequence similarities within ApxIIA and ApxIIIA proteins, which may help in the development of effective vaccines against disease caused by A. pleuropneumoniae. © 2016 The Societies and John Wiley & Sons Australia, Ltd.

Efficacy of a Trivalent Hand, Foot, and Mouth Disease Vaccine against Enterovirus 71 and Coxsackieviruses A16 and A6 in Mice.

PubMed

Caine, Elizabeth A; Fuchs, Jeremy; Das, Subash C; Partidos, Charalambos D; Osorio, Jorge E

2015-11-17

Hand, foot, and mouth disease (HFMD) has recently emerged as a major public health concern across the Asian-Pacific region. Enterovirus 71 (EV71) and Coxsackievirus A16 (CVA16) are the primary causative agents of HFMD, but other members of the Enterovirus A species, including Coxsackievirus A6 (CVA6), can cause disease. The lack of small animal models for these viruses have hampered the development of a licensed HFMD vaccine or antivirals. We have previously reported on the development of a mouse model for EV71 and demonstrated the protective efficacy of an inactivated EV71 vaccine candidate. Here, mouse-adapted strains of CVA16 and CVA6 were produced by sequential passage of the viruses through mice deficient in interferon (IFN) α/β (A129) and α/β and γ (AG129) receptors. Adapted viruses were capable of infecting 3 week-old A129 (CVA6) and 12 week-old AG129 (CVA16) mice. Accordingly, these models were used in active and passive immunization studies to test the efficacy of a trivalent vaccine candidate containing inactivated EV71, CVA16, and CVA6. Full protection from lethal challenge against EV71 and CVA16 was observed in trivalent vaccinated groups. In contrast, monovalent vaccinated groups with non-homologous challenges failed to cross protect. Protection from CVA6 challenge was accomplished through a passive transfer study involving serum raised against the trivalent vaccine. These animal models will be useful for future studies on HFMD related pathogenesis and the efficacy of vaccine candidates.

Effect of passively transferred anti-poliovirus antibodies on seroconversion.

PubMed

Bavdekar, S B; Naik, S; Nadkarni, S S; Kamat, J R; Deshpande, J M; Vaswani, L K

1999-01-01

A prospective study enrolling 50 mother-infant pairs was undertaken to determine the effect of maternal antibodies on poliovirus antibody titres and seroconversion rates in infants and to determine the difference in titres and seroconversion rates following three and five doses of oral poliovaccine (OPV). Cord blood samples and samples collected 4 weeks after 3rd and 5th doses of trivalent oral poliovaccine were processed for estimation of anti-poliovirus antibody titres. These were expressed as geometric mean titres (GMT). Significance was analyzed using unpaired 't' test. The relationship between maternal antibody titres and seroconversion was determined by correlation coefficient test. Post OPV5 titres were significantly higher than post OPV3 titres for type 1 and type 2 polioviruses. Seroconversion rates against type 1, 2 and 3 polioviruses were 92.9%, 100.0% and 92.9% following OPV3 and 100.0%, 100.0% and 93.2% following OPV5. The cord blood titres did not have any relation to post-OPV3 or post-OPV5 titres. Although there is significant passive transfer of poliovirus antibodies across the placenta, this does not affect titres achieved after immunization. Post-OPV5 titres against type 1 and type 2 viruses are significantly higher than post-OPV3 titres. The seroconversion rates following OPV5 are higher than those obtained post-OPV3 but this difference is not statistically significant.

Liposome-antigen-nucleic acid complexes protect mice from lethal challenge with western and eastern equine encephalitis viruses.

PubMed

Phillips, Aaron T; Schountz, Tony; Toth, Ann M; Rico, Amber B; Jarvis, Donald L; Powers, Ann M; Olson, Ken E

2014-02-01

Alphaviruses are mosquito-borne viruses that cause significant disease in animals and humans. Western equine encephalitis virus (WEEV) and eastern equine encephalitis virus (EEEV), two New World alphaviruses, can cause fatal encephalitis, and EEEV is a select agent of concern in biodefense. However, we have no antiviral therapies against alphaviral disease, and current vaccine strategies target only a single alphavirus species. In an effort to develop new tools for a broader response to outbreaks, we designed and tested a novel alphavirus vaccine comprised of cationic lipid nucleic acid complexes (CLNCs) and the ectodomain of WEEV E1 protein (E1ecto). Interestingly, we found that the CLNC component, alone, had therapeutic efficacy, as it increased survival of CD-1 mice following lethal WEEV infection. Immunization with the CLNC-WEEV E1ecto mixture (lipid-antigen-nucleic acid complexes [LANACs]) using a prime-boost regimen provided 100% protection in mice challenged with WEEV subcutaneously, intranasally, or via mosquito. Mice immunized with LANACs mounted a strong humoral immune response but did not produce neutralizing antibodies. Passive transfer of serum from LANAC E1ecto-immunized mice to nonimmune CD-1 mice conferred protection against WEEV challenge, indicating that antibody is sufficient for protection. In addition, the LANAC E1ecto immunization protocol significantly increased survival of mice following intranasal or subcutaneous challenge with EEEV. In summary, our LANAC formulation has therapeutic potential and is an effective vaccine strategy that offers protection against two distinct species of alphavirus irrespective of the route of infection. We discuss plausible mechanisms as well the potential utility of our LANAC formulation as a pan-alphavirus vaccine.

Development of vaccines against pertussis caused by Bordetella holmesii using a mouse intranasal challenge model.

PubMed

Saito, Momoko; Odanaka, Keita; Otsuka, Nao; Kamachi, Kazunari; Watanabe, Mineo

2016-09-01

Bordetella holmesii is recognized as the third causative agent of pertussis (whooping cough) in addition to Bordetella pertussis and Bordetella parapertussis. Pertussis caused by B. holmesii is not rare around the world. However, to date, there is no effective vaccine against B. holmesii. We examined the protective potency of pertussis vaccines available in Japan and vaccines prepared from B. holmesii. A murine model of respiratory infection was exploited to evaluate protective potency. No Japanese commercial pertussis vaccines were effective against B. holmesii. In contrast, a wBH vaccine and an aBH vaccine prepared from B. holmesii were both protective. Passive immunization with sera from mice immunized with aBH vaccine established protection against B. holmesii, indicating that B. holmesii-specific serum antibodies might play an important role in protection. Immuno-proteomic analysis with sera from mice immunized with aBH vaccine revealed that the sera recognized a BipA-like protein of B. holmesii. An aBH vaccine prepared from a BipA-like protein-deficient mutant strain did not have a protective effect against B. holmesii. Taken together, our results suggest that the BipA-like protein plays an important role in the protective efficacy of aBH vaccine. © 2016 The Societies and John Wiley & Sons Australia, Ltd.

Agglutination by anti-capsular polysaccharide antibody is associated with protection against experimental human pneumococcal carriage

PubMed Central

Reiné, J; Zangari, T; Owugha, JT; Pennington, SH; Gritzfeld, JF; Wright, AD; Collins, AM; van Selm, S; de Jonge, MI; Gordon, SB; Weiser, JN; Ferreira, DM

2016-01-01

The ability of pneumococcal conjugate vaccine (PCV) to decrease transmission by blocking the acquisition of colonization has been attributed to herd immunity. We describe the role of mucosal IgG to capsular polysaccharide (CPS) in mediating protection from carriage, translating our findings from a murine model to humans. We used a flow-cytometric assay to quantify antibody-mediated agglutination demonstrating that hyperimmune sera generated against an unencapsulated mutant was poorly agglutinating. Passive immunization with this antiserum was ineffective to block acquisition of colonization compared to agglutinating antisera raised against the encapsulated parent strain. In the human challenge model samples were collected from PCV and control vaccinated adults. In PCV-vaccinated subjects IgG levels to CPS were increased in serum and nasal wash (NW). IgG to the inoculated strain CPS dropped in NW samples after inoculation suggesting its sequestration by colonizing pneumococci. In post-vaccination NW samples pneumococci were heavily agglutinated compared to pre-vaccination samples in subjects protected against carriage. Our results indicate that pneumococcal agglutination mediated by CPS specific antibodies is a key mechanism of protection against acquisition of carriage. Capsule may be the only vaccine target that can elicit strong agglutinating antibody responses, leading to protection against carriage acquisition and generation of herd immunity. PMID:27579859

Virus-like particle-based vaccine against coxsackievirus A6 protects mice against lethal infections.

PubMed

Shen, Chaoyun; Ku, Zhiqiang; Zhou, Yu; Li, Dapeng; Wang, Lili; Lan, Ke; Liu, Qingwei; Huang, Zhong

2016-07-25

Coxsackievirus A6 (CA6) is emerging as one of the major causative agents of hand, foot, and mouth disease (HFMD) worldwide. However, no vaccine is currently available for preventing CA6 infection. Here, we report the development of a virus-like particle (VLP)-based recombinant vaccine for CA6. We produced CA6 VLPs in insect cells by infecting the cells with a baculovirus coexpressing the genes encoding CA6 P1 and 3CD. Biochemical analyses showed that the produced VLPs consisted of VP0, VP1, and VP3 capsid subunit proteins generated by the cleavage of P1 by 3CD. Mice immunized with these VLPs produced CA6-specific serum antibodies. Passive transfer of antisera from CA6 VLP-immunized mice protected recipient mice from lethal infections caused by homologous and heterologous CA6 strains. Moreover, active immunization of mice with CA6 VLPs efficiently conferred protection against both homologous and heterologous CA6 infections. These results suggested that CA6 VLP-based recombinant vaccine is a promising candidate vaccine for preventing CA6 infection and can be incorporated into a multivalent HFMD vaccine formulation to achieve broad-spectrum and effective prevention of this disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

MD-2 is required for disulfide HMGB1–dependent TLR4 signaling

PubMed Central

Wang, Haichao; Ju, Zhongliang; Ragab, Ahmed A.; Lundbäck, Peter; Long, Wei; Valdes-Ferrer, Sergio I.; He, Mingzhu; Pribis, John P.; Li, Jianhua; Lu, Ben; Gero, Domokos; Szabo, Csaba; Antoine, Daniel J.; Harris, Helena E.; Golenbock, Doug T.; Meng, Jianmin; Roth, Jesse; Chavan, Sangeeta S.; Andersson, Ulf; Billiar, Timothy R.; Al-Abed, Yousef

2015-01-01

Innate immune receptors for pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) orchestrate inflammatory responses to infection and injury. Secreted by activated immune cells or passively released by damaged cells, HMGB1 is subjected to redox modification that distinctly influences its extracellular functions. Previously, it was unknown how the TLR4 signalosome distinguished between HMGB1 isoforms. Here we demonstrate that the extracellular TLR4 adaptor, myeloid differentiation factor 2 (MD-2), binds specifically to the cytokine-inducing disulfide isoform of HMGB1, to the exclusion of other isoforms. Using MD-2–deficient mice, as well as MD-2 silencing in macrophages, we show a requirement for HMGB1-dependent TLR4 signaling. By screening HMGB1 peptide libraries, we identified a tetramer (FSSE, designated P5779) as a specific MD-2 antagonist preventing MD-2–HMGB1 interaction and TLR4 signaling. P5779 does not interfere with lipopolysaccharide-induced cytokine/chemokine production, thus preserving PAMP-mediated TLR4–MD-2 responses. Furthermore, P5779 can protect mice against hepatic ischemia/reperfusion injury, chemical toxicity, and sepsis. These findings reveal a novel mechanism by which innate systems selectively recognize specific HMGB1 isoforms. The results may direct toward strategies aimed at attenuating DAMP-mediated inflammation while preserving antimicrobial immune responsiveness. PMID:25559892

Measles, rubella, and varicella among the crew of a cruise ship sailing from Florida, United States, 2006.

PubMed

Mitruka, Kiren; Felsen, Christina B; Tomianovic, Danitza; Inman, Barry; Street, Karen; Yambor, Phyllis; Reef, Susan E

2012-07-01

Cruise ship outbreaks of vaccine-preventable diseases (VPD) such as rubella and varicella have been previously associated with introduction and spread among susceptible crew members originating from countries with endemic transmission of these diseases. During February to April 2006, we investigated a cluster of rash illnesses due to measles, rubella, or varicella on a cruise ship sailing from Florida to the Caribbean. Case-finding measures included review of medical logs, active surveillance for rash illness among crew members, and passive surveillance for rash illness in the ship's infirmary lasting two incubation periods from the last case of measles. Passengers with potential exposure to these VPD were notified by letters. All susceptible crew members with potential exposure were administered the measles, mumps, and rubella vaccine after informed consent. A total of 16 cases were identified only among crew members: 1 rubella, 3 measles (two-generation spread), 11 varicella (three-generation spread), and 1 unknown diagnosis. Of 1,197 crew members evaluated, 4 had proof of immunity to measles and rubella. Based on passive surveillance, no cases were identified among passengers, the majority of whom resided in the United States. The international makeup of the population aboard cruise ships combined with their semi-enclosed environment has the potential to facilitate introduction and spread of VPD such as measles, rubella, and varicella onboard and into communities. Cruise lines should ensure crew members have evidence of immunity to these diseases. Passengers should be up to date with all vaccinations, including those that are travel-specific, prior to embarking on cruise travel. Published 2012. This article is a U.S. Government work and is in the public domain in the USA.

The effect of video-guidance on passive movement in patients with cerebral palsy: fMRI study.

PubMed

Dinomais, Mickael; Chinier, Eva; Lignon, Gregoire; Richard, Isabelle; Ter Minassian, Aram; Tich, Sylvie Nguyen The

2013-10-01

In patients with cerebral palsy (CP), neuroimaging studies have demonstrated that passive movement and action-observation tasks have in common to share neuronal activation in all or part of areas involved in motor system. Action observation with simultaneous congruent passive movements may have additional effects in the recruitment of brain motor areas. The aim of this functional magnetic resonance imaging (fMRI) study was to examine brain activation in patients with unilateral CP during passive movement with and without simultaneous observation of simple hand movement. Eighteen patients with unilateral CP (fourteen male, mean age 14 years and 2 months) participated in the study. Using fMRI block design, brain activation following passive simple opening-closing hand movement of either the paretic or nonparetic hand with and without simultaneous observation of a similar movement performed by either the left or right hand of an actor was compared. Passive movement of the paretic hand performed simultaneously to the observation of congruent movement activated more "higher motor areas" including contralesional pre-supplementary motor area, superior frontal gyrus (extending to premotor cortex), and superior and inferior parietal regions than nonvideo-guided passive movement of the paretic hand. Passive movement of the paretic hand recruited more ipsilesional sensorimotor areas compared to passive movement of the nonparetic hand. Our study showed that the combination of observation of congruent hand movement simultaneously to passive movement of the paretic hand recruits more motor areas, giving neuronal substrate to propose video-guided passive movement of paretic hand in CP rehabilitation. Copyright © 2013 Elsevier Ltd. All rights reserved.

The safety of yellow fever vaccine 17D or 17DD in children, pregnant women, HIV+ individuals, and older persons: systematic review.

PubMed

Thomas, Roger E; Lorenzetti, Diane L; Spragins, Wendy; Jackson, Dave; Williamson, Tyler

2012-02-01

Yellow fever vaccine provides long-lasting immunity. Rare serious adverse events after vaccination include neurologic or viscerotropic syndromes or anaphylaxis. We conducted a systematic review of adverse events associated with yellow fever vaccination in vulnerable populations. Nine electronic bibliographic databases and reference lists of included articles were searched. Electronic databases identified 2,415 abstracts for review, and 32 abstracts were included in this review. We identified nine studies of adverse events in infants and children, eight studies of adverse events in pregnant women, nine studies of adverse events in human immunodeficiency virus-positive patients, five studies of adverse events in persons 60 years and older, and one study of adverse events in individuals taking immunosuppressive medications. Two case studies of maternal-neonate transmission resulted in serious adverse events, and the five passive surveillance databases identified very small numbers of cases of yellow fever vaccine-associated viscerotropic disease, yellow fever vaccine-associated neurotropic disease, and anaphylaxis in persons ≥ 60 years. No other serious adverse events were identified in the other studies of vulnerable groups.

Psychosocial predictors of immune response following bone marrow transplantation.

PubMed

Pulgar, Ángeles; Garrido, Sergio; Alcalá, Antonio; Reyes del Paso, Gustavo A

2012-01-01

This study analyzed the relationship between some psychosocial variables (depression, anxiety, stress, coping strategies, social support, optimism, rationality, and need for harmony) and clinical parameters indicative of immunological response after bone marrow transplantation (BMT; day of engraftment, number of infections and hemoglobin level) while controlling for demographic variables (age, educative level, civil state, and time from cancer diagnosis). Thirty-one post BMT hematological cancer patients were evaluated. Results show that higher educative levels are associated to lower number of infections, while age is associated with a delay in the time of engraftment; coping strategies, specially redefinition of the situation, relaxation, stoicism and passivity, are positively associated with the three clinical indices; depression is positively associated to number of infections during the hospitalization period; and rationality is associated with lower hemoglobin levels. These results suggest that psychosocial variables, especially coping strategies, play an important role in determining the immunological response after BMT.

Stochastic dynamics of genetic broadcasting networks

NASA Astrophysics Data System (ADS)

Potoyan, Davit; Wolynes, Peter

The complex genetic programs of eukaryotic cells are often regulated by key transcription factors occupying or clearing out of a large number of genomic locations. Orchestrating the residence times of these factors is therefore important for the well organized functioning of a large network. The classic models of genetic switches sidestep this timing issue by assuming the binding of transcription factors to be governed entirely by thermodynamic protein-DNA affinities. Here we show that relying on passive thermodynamics and random release times can lead to a ''time-scale crisis'' of master genes that broadcast their signals to large number of binding sites. We demonstrate that this ''time-scale crisis'' can be resolved by actively regulating residence times through molecular stripping. We illustrate these ideas by studying the stochastic dynamics of the genetic network of the central eukaryotic master regulator NFκB which broadcasts its signals to many downstream genes that regulate immune response, apoptosis etc.

The Passive Film Growth Mechanism of New Corrosion-Resistant Steel Rebar in Simulated Concrete Pore Solution: Nanometer Structure and Electrochemical Study

PubMed Central

Jiang, Jin-yang; Wang, Danqian; Chu, Hong-yan; Ma, Han; Liu, Yao; Gao, Yun; Shi, Jinjie; Sun, Wei

2017-01-01

An elaborative study was carried out on the growth mechanism and properties of the passive film for a new kind of alloyed corrosion-resistant steel (CR steel). The passive film naturally formed in simulated concrete pore solutions (pH = 13.3). The corrosion resistance was evaluated by various methods including open circuit potential (OCP), linear polarization resistance (LPR) measurements, and electrochemical impedance spectroscopy (EIS). Meanwhile, the 2205 duplex stainless steel (SS steel) was evaluated for comparison. Moreover, the passive film with CR steel was studied by means of X-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM), Atomic Force Microscope (AFM), and the Mott‑Schottky approach. The results showed that the excellent passivity of CR steel could be detected in a high alkaline environment. The grain boundaries between the fine passive film particles lead to increasing Cr oxide content in the later passivation stage. The filling of cation vacancies in the later passivation stage as well as the orderly crystalized inner layer contributed to the excellent corrosion resistance of CR steel. A passive film growth model for CR steel was proposed. PMID:28772772

The Passive Film Growth Mechanism of New Corrosion-Resistant Steel Rebar in Simulated Concrete Pore Solution: Nanometer Structure and Electrochemical Study.

PubMed

Jiang, Jin-Yang; Wang, Danqian; Chu, Hong-Yan; Ma, Han; Liu, Yao; Gao, Yun; Shi, Jinjie; Sun, Wei

2017-04-14

An elaborative study was carried out on the growth mechanism and properties of the passive film for a new kind of alloyed corrosion-resistant steel (CR steel). The passive film naturally formed in simulated concrete pore solutions (pH = 13.3). The corrosion resistance was evaluated by various methods including open circuit potential (OCP), linear polarization resistance (LPR) measurements, and electrochemical impedance spectroscopy (EIS). Meanwhile, the 2205 duplex stainless steel (SS steel) was evaluated for comparison. Moreover, the passive film with CR steel was studied by means of X-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM), Atomic Force Microscope (AFM), and the Mott‑Schottky approach. The results showed that the excellent passivity of CR steel could be detected in a high alkaline environment. The grain boundaries between the fine passive film particles lead to increasing Cr oxide content in the later passivation stage. The filling of cation vacancies in the later passivation stage as well as the orderly crystalized inner layer contributed to the excellent corrosion resistance of CR steel. A passive film growth model for CR steel was proposed.

Immunotoxic effect of thiamethoxam in immunized mice with Brucella abortus cultural filtrate antigen

PubMed Central

Salema, L. H.; Alwan, M. J.; Yousif, Afaf Abdulrahman

2016-01-01

Aim: This study was planned for determination the toxic effect of thiamethoxam (TMX) in immunized mice with Brucella abortus culture filtrate antigen (CFBAgs) (as a vaccine) and its role of TMX on decrease activity of B. abortus antigen on eliciting of humoral and cellular immunity. Materials and Methods: To achieve these goals 60 female mice were used, 7-8 weeks age, they were divided equally into three groups (20 in each group) and treated as follows: 1st group: Mice were immunized with CFBAgs intraperitoneally in two doses, 2 weeks intervals with (protein concentration 2 mg\\ml), 2nd group: Mice immunized as in the 1st group and was administrated orally with 1/10 lethal dose 50% of TMX (83.7 mg/kg B.W.) for 4 weeks daily, 3rd group was administrated orally with 0.3 ml normal saline served as a control group. At day 28 post immunization (PI) delayed type hypersensitivity (skin test) was done, and serum samples were collected at day 30 (PI) for detection of passive hemagglutination test (PHA); interferon gamma (IFN-γ) which was done by enzyme-linked immunosorbent assay test in addition to phagocytes assay. Results: The results of skin test post injection with soluble antigen of B. abortus intradermally showed a high significantly mean values at p≤0.05 of footpad skin thickness in the 1st group of mice which recorded (0.51±0.002 mm) as compared with the 2nd group of mice which showed (0.08±0.002 mm) after 24 h; the mean values of skin thickness were declined in the 1st mice (0.46±0.002) and 2nd mice (0.070±0.001) at 48 h; control group showed a negative results. These results were agreed with results of serum levels of IFN-γ (pg/ml) that showed that a significant increase the vaccinated 1st group (406.36±1.52), than those values in the 2nd group (151.61±0.89) and negative result in 3rd group (46.47±0.60), in addition to results of PHA test which showed a significant increase in antibody titer in the 1st group (139±12.16) with low level of serum antibody in the 2nd group (7.66±0.33). Phagocytic ratio results in the 1st group showed an increase to reach (18.55±0.44) than a ratio in the 2nd group (13.24±0.32) and the control group (5.46±0.25). Conclusion: It was concluded that TMX induced suppression of humoral and cellular immune responses in immunized mice with CFBAgs. PMID:28096613

Fiber Bragg Grating Sensors for Harsh Environments

PubMed Central

Mihailov, Stephen J.

2012-01-01

Because of their small size, passive nature, immunity to electromagnetic interference, and capability to directly measure physical parameters such as temperature and strain, fiber Bragg grating sensors have developed beyond a laboratory curiosity and are becoming a mainstream sensing technology. Recently, high temperature stable gratings based on regeneration techniques and femtosecond infrared laser processing have shown promise for use in extreme environments such as high temperature, pressure or ionizing radiation. Such gratings are ideally suited for energy production applications where there is a requirement for advanced energy system instrumentation and controls that are operable in harsh environments. This paper will present a review of some of the more recent developments. PMID:22438744

Remembering Emil von Behring: from Tetanus Treatment to Antibody Cooperation with Phagocytes

PubMed Central

2017-01-01

ABSTRACT A century ago, Emil von Behring passed away. He was the first to be honored by the Nobel Prize for Medicine in 1901 for the successful therapy of diphtheria and tetanus, which he had developed from the bench to the bed. He also contributed to the foundation of immunology, since his therapy was based on passive immunization with specific antisera. Being an ambitious character, he did not shy away from friction with his colleagues Paul Ehrlich and Elias Metchnikoff and his mentor, Robert Koch. Behring was not only an excellent translational researcher but also a successful entrepreneur and early proponent of public-private partnerships. PMID:28246359

The pathogenesis of Ebola hemorrhagic fever.

PubMed

Takada, A; Kawaoka, Y

2001-10-01

Ebola virus causes lethal hemorrhagic disease in humans, yet there are still no satisfactory biological explanations to account for its extreme virulence. This review focuses on recent findings relevant to understanding the pathogenesis of Ebola virus infection and developing vaccines and effective therapy. The available data suggest that the envelope glycoprotein and the interaction of some viral proteins with the immune system are likely to play important roles in the extraordinary pathogenicity of this virus. There are also indications that genetically engineered vaccines, including plasmid DNA and viral vectors expressing Ebola virus proteins, and passive transfer of neutralizing antibodies could be feasible options for the control of Ebola virus-associated disease.

Immunotherapy targeting α-synuclein, with relevance for future treatment of Parkinson's disease and other Lewy body disorders.

PubMed

Lindström, Veronica; Ihse, Elisabet; Fagerqvist, Therese; Bergström, Joakim; Nordström, Eva; Möller, Christer; Lannfelt, Lars; Ingelsson, Martin

2014-01-01

Immunotherapy targeting α-synuclein has evolved as a potential therapeutic strategy for neurodegenerative diseases, such as Parkinson's disease, and initial studies on cellular and animal models have shown promising results. α-synuclein vaccination of transgenic mice reduced the number of brain inclusions, whereas passive immunization studies demonstrated that antibodies against the C-terminus of α-synuclein can pass the blood-brain barrier and affect the pathology. In addition, preliminary evidence suggests that transgenic mice treated with an antibody directed against α-synuclein oligomers/protofibrils resulted in reduced levels of such species in the CNS. The underlying mechanisms of immunotherapy are not yet fully understood, but may include antibody-mediated clearance of pre-existing aggregates, prevention of protein propagation between cells and microglia-dependent protein clearance. Thus, immunotherapy targeting α-synuclein holds promise, but needs to be further developed as a future disease-modifying treatment in Parkinson's disease and other α-synucleinopathies.

Differential immunosuppression by Campoletis chlorideae eggs and ichnovirus in larvae of Helicoverpa armigera and Spodoptera exigua.

PubMed

Han, Li-Bin; Yin, Li-Hong; Huang, Ling-Qiao; Wang, Chen-Zhu

2015-09-01

The ichneumonid wasp, Campoletis chlorideae Uchida, successfully develops in the cotton bollworm Helicoverpa armigera (Hübner), but rarely survives in the beet armyworm Spodoptera exigua (Hübner) due to the encapsulation by host immunity. In this study, we investigated the role of C. chlorideae ichnovirus (CcIV) and eggs in the evasion of the host immune system. Washed eggs of different types, immature, mature, newly laid, or pretreated with protease K, were injected alone or with the calyx fluid containing CcIV into the larvae of H. armigera and S. exigua. In H. armigera, when injected with washed eggs alone, only 9.5% of the mature eggs were encapsulated at 24h post-injection. This is much lower than that of the immature eggs (100%), mature eggs pretreated with protease K (100%) and newly laid eggs (54.4%). No encapsulation was observed when the washed eggs were co-injected with calyx fluid at 24h post-injection. Conversely, the eggs in all treatments were encapsulated in S. exigua. Electron microscopic observations of parasitoid eggs showed structural differences between the surfaces of the mature and other kinds of eggs. The injected CcIV decreased the numbers of host hemocytes and suppressed the spreading ability of plasmatocytes and granulocytes in H. armigera, but had little effect on the hemocytes from S. exigua. In conclusion, the C. chlorideae egg provides a passive protection against encapsulation by itself, and CcIV supplies an active protection through disrupting host immune responses. These coordinated protections are host-specific, implying their role in host range determination. Copyright © 2015 Elsevier Inc. All rights reserved.

Antibodies induced by the HA2 glycopolypeptide of influenza virus haemagglutinin improve recovery from influenza A virus infection.

PubMed

Gocník, M; Fislová, T; Mucha, V; Sládková, T; Russ, G; Kostolansky, F; Varecková, E

2008-04-01

The haemagglutinin (HA) of influenza A virus consists of two glycopolypeptides designated HA1 and HA2. Antibodies recognizing HA1 inhibit virus haemagglutination, neutralize virus infectivity and provide good protection against infection, but do not cross-react with the HA of other subtypes. Little is known regarding the biological activities of antibodies against HA2. To study the role of antibodies directed against HA2 during influenza virus infection, two vaccinia virus recombinants (rVVs) were used expressing chimeric molecules of HA, in which HA1 and HA2 were derived from different HA subtypes. The KG-11 recombinant expressed HA1 from A/PR/8/34 (H1N1) virus and HA2 from A/NT/60 (H3N2) virus, whilst KG-12 recombinant expressed HA1 from A/NT/60 virus and HA2 from A/PR/8/34 virus. Immunization of BALB/c mice with rVV expressing HA2 of the HA subtype homologous to the challenge virus [A/PR/8/34 (H1N1) or A/Mississippi/1/85 (H3N2)] did not prevent virus infection, but nevertheless resulted in an increase in mice survival and faster elimination of virus from the lungs. Passive immunization with antibodies purified from mice immunized with rVVs confirmed that antibodies against HA2 were responsible for the described effect on virus infection. Based on the facts that HA2 is a rather conserved part of the HA and that antibodies against HA2, as shown here, may moderate virus infection, future vaccine design should deal with the problem of how to increase the HA2 antibody response.

A close look at brain dynamics: cells and vessels seen by in vivo two-photon microscopy.

PubMed

Fumagalli, Stefano; Ortolano, Fabrizio; De Simoni, Maria-Grazia

2014-10-01

The cerebral vasculature has a unique role in providing a constant supply of oxygen and nutrients to ensure normal brain functions. Blood vessels that feed the brain are far from being simply channels for passive transportation of fluids. They form complex structures made up of different cell types. These structures regulate blood supply, local concentrations of O2 and CO2, transport of small molecules, trafficking of plasma cells and fine cerebral functions in normal and diseased brains. Until few years ago, analysis of these functions has been typically based on post mortem techniques, whose interpretation is limited by the need for tissue processing at specific times. For a reliable and effective picture of the dynamic processes in the central nervous system, real-time information in vivo is required. There are now few in vivo systems, among which two-photon microscopy (2-PM) is a truly innovative tool for studying the brain. 2-PM has been used to dissect specific aspects of vascular and immune cell dynamics in the context of neurological diseases, providing exciting results that could not have been obtained with conventional methods. This review summarizes the latest findings on vascular and immune system action in the brain, with particular focus on the dynamic responses after ischemic brain injury. 2-PM has helped define the hierarchical architecture of the brain vasculature, the dynamic interaction between the vasculature and immune cells recruited to lesion sites, the effects of blood flow on neuronal and microglial activity and the ability of cells of the neurovascular unit to regulate blood flow. Copyright © 2014 Elsevier Ltd. All rights reserved.

Lack of allergy to timothy grass pollen is not a passive phenomenon but associated with the allergen-specific modulation of immune reactivity.

PubMed

Hinz, D; Seumois, G; Gholami, A M; Greenbaum, J A; Lane, J; White, B; Broide, D H; Schulten, V; Sidney, J; Bakhru, P; Oseroff, C; Wambre, E; James, E A; Kwok, W W; Peters, B; Vijayanand, P; Sette, A

2016-05-01

Timothy grass (TG) pollen is a common seasonal airborne allergen associated with symptoms ranging from mild rhinitis to severe asthma. The aim of this study was to characterize changes in TG-specific T cell responses as a function of seasonality. Peripheral blood mononuclear cells (PBMCs) obtained from allergic individuals and non-allergic controls, either during the pollen season or out of season, were stimulated with either TG extract or a pool of previously identified immunodominant antigenic regions. PBMCs from allergic subjects exhibit higher IL-5 and IL-10 responses in season than when collected out of season. In the case of non-allergic subjects, as expected we observed lower IL-5 responses and robust production of IFN-γ compared to allergic individuals. Strikingly, non-allergic donors exhibited an opposing pattern, with decreased immune reactivity in season. The broad down-regulation in non-allergic donors indicates that healthy individuals are not oblivious to allergen exposure, but rather react with an active modulation of responses following the antigenic stimulus provided during the pollen season. Transcriptomic analysis of allergen-specific T cells defined genes modulated in concomitance with the allergen exposure and inhibition of responses in non-allergic donors. Magnitude and functionality of T helper cell responses differ substantially in season vs. out of season in allergic and non-allergic subjects. The results indicate the specific and opposing modulation of immune responses following the antigenic stimulation during the pollen season. This seasonal modulation reflects the enactment of specific molecular programmes associated with health and allergic disease. © 2015 John Wiley & Sons Ltd.

Antibodies against In Vivo-Expressed Antigens Are Sufficient To Protect against Lethal Aerosol Infection with Burkholderia mallei and Burkholderia pseudomallei.

PubMed

Zimmerman, Shawn M; Dyke, Jeremy S; Jelesijevic, Tomislav P; Michel, Frank; Lafontaine, Eric R; Hogan, Robert J

2017-08-01

Burkholderia mallei , a facultative intracellular bacterium and tier 1 biothreat, causes the fatal zoonotic disease glanders. The organism possesses multiple genes encoding autotransporter proteins, which represent important virulence factors and targets for developing countermeasures in pathogenic Gram-negative bacteria. In the present study, we investigated one of these autotransporters, BatA, and demonstrate that it displays lipolytic activity, aids in intracellular survival, is expressed in vivo , elicits production of antibodies during infection, and contributes to pathogenicity in a mouse aerosol challenge model. A mutation in the batA gene of wild-type strain ATCC 23344 was found to be particularly attenuating, as BALB/c mice infected with the equivalent of 80 median lethal doses cleared the organism. This finding prompted us to test the hypothesis that vaccination with the batA mutant strain elicits protective immunity against subsequent infection with wild-type bacteria. We discovered that not only does vaccination provide high levels of protection against lethal aerosol challenge with B. mallei ATCC 23344, it also protects against infection with multiple isolates of the closely related organism and causative agent of melioidosis, Burkholderia pseudomallei Passive-transfer experiments also revealed that the protective immunity afforded by vaccination with the batA mutant strain is predominantly mediated by IgG antibodies binding to antigens expressed exclusively in vivo Collectively, our data demonstrate that BatA is a target for developing medical countermeasures and that vaccination with a mutant lacking expression of the protein provides a platform to gain insights regarding mechanisms of protective immunity against B. mallei and B. pseudomallei , including antigen discovery. Copyright © 2017 American Society for Microbiology.

A cell wall protein-based vaccine candidate induce protective immune response against Sporothrix schenckii infection.

PubMed

Portuondo, Deivys Leandro; Batista-Duharte, Alexander; Ferreira, Lucas Souza; Martínez, Damiana Téllez; Polesi, Marisa Campos; Duarte, Roberta Aparecida; de Paula E Silva, Ana Carolina Alves; Marcos, Caroline Maria; Almeida, Ana Marisa Fusco de; Carlos, Iracilda Zeppone

2016-02-01

Sporotrichosis is a subcutaneous mycosis caused by several closely related thermo-dimorphic fungi of the Sporothrix schenckii species complex, affecting humans and other mammals. In the last few years, new strategies have been proposed for controlling sporotrichosis owning to concerns about its growing incidence in humans, cats, and dogs in Brazil, as well as the toxicity and limited efficacy of conventional antifungal drugs. In this study, we assessed the immunogenicity and protective properties of two aluminum hydroxide (AH)-adsorbed S. schenckii cell wall protein (ssCWP)-based vaccine formulations in a mouse model of systemic S. schenckii infection. Fractioning by SDS-PAGE revealed nine protein bands, two of which were functionally characterized: a 44kDa peptide hydrolase and a 47kDa enolase, which was predicted to be an adhesin. Sera from immunized mice recognized the 47kDa enolase and another unidentified 71kDa protein, whereas serum from S. schenckii-infected mice recognized both these proteins plus another unidentified 9.4kDa protein. Furthermore, opsonization with the anti-ssCWP sera led to markedly increased phagocytosis and was able to strongly inhibit the fungus' adhesion to fibroblasts. Immunization with the higher-dose AH-adjuvanted formulation led to increased ex vivo release of IL-12, IFN-γ, IL-4, and IL-17, whereas only IL-12 and IFN-γ were induced by the higher-dose non-adjuvanted formulation. Lastly, passive transference of the higher-dose AH-adjuvanted formulation's anti-ssCWP serum was able to afford in vivo protection in a subsequent challenge with S. schenckii, becoming a viable vaccine candidate for further testing. Copyright © 2015 Elsevier GmbH. All rights reserved.

Murine Visceral Leishmaniasis: IgM and Polyclonal B-Cell Activation Lead to Disease Exacerbation

PubMed Central

Deak, Eszter; Jayakumar, Asha; Wing Cho, Ka; Goldsmith-Pestana, Karen; Dondji, Blaise; Lambris, John D.; McMahon-Pratt, Diane

2010-01-01

In visceral leishmaniasis, the draining lymph node (DLN) is the initial site for colonization and establishment of infection after intradermal transmission by the sand fly vector; however, little is known about the developing immune response within this site. Using an intradermal infection model, which allows for parasite visceralization, we have examined the ongoing immune responses in the DLN of BALB/c mice infected with L. infantum. Although not unexpected, at early times post-infection there is a marked B cell expansion in the DLN, which persists throughout infection. However, the characteristics of this response were of interest; as early as day 7 post-infection, polyclonal antibodies (TNP, OVA, chromatin) were observed and the levels appeared comparable to the specific anti-leishmania response. Although B-cell-deficient JHD BALB/c mice are relatively resistant to infection, neither B-cell-derived IL-10 nor B-cell antigen presentation appear to be primarily responsible for the elevated parasitemia. However, passive transfer and reconstitution of JHD BALB/c with secretory immunoglobulins, (IgM or IgG; specific or non-specific immune complexes) results in increased susceptibility to L. infantum infection. Further, JHD BALB/c mice transgenetically reconstituted to secrete IgM demonstrated exacerbated disease in comparison to wild type BALB/c mice as early as 2 days post-infection. Evidence suggests that complement activation (generation of C5a) and signaling via the C5aR (CD88) is related to the disease exacerbation caused by IgM rather than cytokine levels (IL-10 or IFN-γ). Overall these studies indicate that polyclonal B cell activation, which is known to be associated with human visceral leishmaniasis, is an early and intrinsic characteristic of disease and may represent a target for therapeutic intervention. PMID:20213734

Antibodies against In Vivo-Expressed Antigens Are Sufficient To Protect against Lethal Aerosol Infection with Burkholderia mallei and Burkholderia pseudomallei

PubMed Central

Zimmerman, Shawn M.; Dyke, Jeremy S.; Jelesijevic, Tomislav P.; Michel, Frank; Lafontaine, Eric R.

2017-01-01

ABSTRACT Burkholderia mallei, a facultative intracellular bacterium and tier 1 biothreat, causes the fatal zoonotic disease glanders. The organism possesses multiple genes encoding autotransporter proteins, which represent important virulence factors and targets for developing countermeasures in pathogenic Gram-negative bacteria. In the present study, we investigated one of these autotransporters, BatA, and demonstrate that it displays lipolytic activity, aids in intracellular survival, is expressed in vivo, elicits production of antibodies during infection, and contributes to pathogenicity in a mouse aerosol challenge model. A mutation in the batA gene of wild-type strain ATCC 23344 was found to be particularly attenuating, as BALB/c mice infected with the equivalent of 80 median lethal doses cleared the organism. This finding prompted us to test the hypothesis that vaccination with the batA mutant strain elicits protective immunity against subsequent infection with wild-type bacteria. We discovered that not only does vaccination provide high levels of protection against lethal aerosol challenge with B. mallei ATCC 23344, it also protects against infection with multiple isolates of the closely related organism and causative agent of melioidosis, Burkholderia pseudomallei. Passive-transfer experiments also revealed that the protective immunity afforded by vaccination with the batA mutant strain is predominantly mediated by IgG antibodies binding to antigens expressed exclusively in vivo. Collectively, our data demonstrate that BatA is a target for developing medical countermeasures and that vaccination with a mutant lacking expression of the protein provides a platform to gain insights regarding mechanisms of protective immunity against B. mallei and B. pseudomallei, including antigen discovery. PMID:28507073

Novel approaches for immunotherapeutic intervention in Alzheimer's disease.

PubMed

Vasilevko, Vitaly; Cribbs, David H

2006-07-01

Immunotherapy can attenuate amyloid neuropathology and improve cognitive function in transgenic models of Alzheimer's disease. However, the first clinical trial was halted when 6% of the Alzheimer's patients developed aseptic meningoencephalitis. Postmortem analysis of two cases with meningoencephalitis showed robust glial activation, T-cell infiltration and sporadic clearance of Abeta. Interestingly, transgenic mouse models of Alzheimer's disease failed as predictors of these adverse inflammatory events. However there are now several studies with amyloid precursor protein transgenic mice that have reported an increased risk of microhemorrhages at sites of cerebrovascular amyloid deposits and because approximately 80% of Alzheimer's patient's have cerebrovascular pathology, there is concern regarding clinical trials using passive administration of humanized anti-Abeta antibodies. Although many studies have now been published on immunotherapy in mouse models, the mechanism(s) of antibody-mediated clearance of beta-amyloid from the brain, and the cause of the antibody-induced microhemorrhages remain unclear. In this review, we will discuss the most recent results from the first clinical trial, offer speculation on possible causes for the failure of the trial, review data on antibody-mediated clearance mechanisms, explore the role of complement and inflammation in the clearance of beta-amyloid, and suggest novel strategies for avoiding problems in future clinical trials. The central hypothesis being proposed in this review is that anti-Abeta antibodies delivered directly to the CNS at the sites of amyloid deposits will be far more effective at clearing Abeta and safer than active or passive immunization strategies where the majority of the antibodies are in the periphery.

Influence of Passive Joint Stiffness on Proprioceptive Acuity in Individuals With Functional Instability of the Ankle.

PubMed

Marinho, Hellen Veloso Rocha; Amaral, Giovanna Mendes; de Souza Moreira, Bruno; Araújo, Vanessa Lara; Souza, Thales Rezende; Ocarino, Juliana Melo; da Fonseca, Sérgio Teixeira

2017-12-01

Study Design Controlled laboratory study, cross-sectional. Background Deficits in ankle proprioceptive acuity have been reported in persons with functional instability of the ankle. Passive stiffness has been proposed as a possible mechanism underlying proprioceptive acuity. Objective To compare proprioceptive acuity and passive ankle stiffness in persons with and without functional ankle instability, and to assess the influence of passive joint stiffness on proprioceptive acuity in persons with functional ankle instability. Methods A sample of 18 subjects with and 18 without complaints of functional ankle instability following lateral ankle sprain participated. An isokinetic dynamometer was used to compare motion perception threshold, passive position sense, and passive ankle stiffness between groups. To evaluate the influence of passive stiffness on proprioceptive acuity, individuals in the lateral functional ankle instability group were divided into 2 subgroups: "high" and "low" passive ankle stiffness. Results The functional ankle instability group exhibited increased motion perception threshold when compared with the corresponding limb of the control group. Between-group differences were not found for passive position sense and passive ankle stiffness. Those in the functional ankle instability group with higher passive ankle stiffness had smaller motion perception thresholds than those with lower passive ankle stiffness. Conclusion Unlike motion perception threshold, passive position sense is not affected by the presence of functional ankle instability. Passive ankle stiffness appears to influence proprioceptive acuity in persons with functional ankle instability. J Orthop Sports Phys Ther 2017;47(12):899-905. Epub 7 Oct 2017. doi:10.2519/jospt.2017.7030.

Evaluating the Relationship between Equilibrium Passive ...

EPA Pesticide Factsheets

This review evaluates passive sampler uptake of hydrophobic organic contaminants (HOCs) as it relates to organism bioaccumulation in the water column and interstitial water. Fifty-five studies were found where both passive samplers and organism bioaccumulation were used to measured water quality. Of these investigations, 19 provided direct comparisons relating passive sampler concentrations and organism bioaccumulation. Passive sampling polymers included in the review were: low density polyethylene (LDPE); polyoxymethylene (POM); and polydimethylsiloxane (PDMS), and organisms ranged from polychaetes and oligochaetes to bivalves, aquatic insects, and gastropods. Log-linear regressions correlating bioaccumulation (CL) and passive sampler concentration (CPS) were used to assess the strength of observed relationships. In general, the passive sampler concentrations resulted in statistically-significant, logarithmic, predictive relationships, most of which were within one to two orders of magnitude of measured bioaccumulation. Overall, bioaccumulation values were greater than passive sampler concentrations. A mean ratio of CL to CPS was 10.8 ± 18.4 (n = 609) for available data. Given that all studies presented resulted in a strong CL versus CPS relationship suggests that using passive sampling as a surrogate for organism bioaccumulation is viable when biomonitoring organisms are not available. Passive sampling based measurements can provide useful information for ma

Active and Passive Fatigue in Simulated Driving: Discriminating Styles of Workload Regulation and Their Safety Impacts

PubMed Central

Saxby, Dyani J.; Matthews, Gerald; Warm, Joel S.; Hitchcock, Edward M.; Neubauer, Catherine

2015-01-01

Despite the known dangers of driver fatigue, it is a difficult construct to study empirically. Different forms of task-induced fatigue may differ in their effects on driver performance and safety. Desmond and Hancock (2001) defined active and passive fatigue states that reflect different styles of workload regulation. In 2 driving simulator studies we investigated the multidimensional subjective states and safety outcomes associated with active and passive fatigue. Wind gusts were used to induce active fatigue, and full vehicle automation to induce passive fatigue. Drive duration was independently manipulated to track the development of fatigue states over time. Participants were undergraduate students. Study 1 (N = 108) focused on subjective response and associated cognitive stress processes, while Study 2 (N = 168) tested fatigue effects on vehicle control and alertness. In both studies the 2 fatigue manipulations produced different patterns of subjective response reflecting different styles of workload regulation, appraisal, and coping. Active fatigue was associated with distress, overload, and heightened coping efforts, whereas passive fatigue corresponded to large-magnitude declines in task engagement, cognitive underload, and reduced challenge appraisal. Study 2 showed that only passive fatigue reduced alertness, operationalized as speed of braking and steering responses to an emergency event. Passive fatigue also increased crash probability, but did not affect a measure of vehicle control. Findings support theories that see fatigue as an outcome of strategies for managing workload. The distinction between active and passive fatigue is important for assessment of fatigue and for evaluating automated driving systems which may induce dangerous levels of passive fatigue. PMID:24041288

Passive vaccination with a human monoclonal antibody: generation of antibodies and studies for efficacy in Bacillus anthracis infections.

PubMed

vor dem Esche, Ulrich; Huber, Maria; Zgaga-Griesz, Andrea; Grunow, Roland; Beyer, Wolfgang; Hahn, Ulrike; Bessler, Wolfgang G

2011-07-01

A major difficulty in creating human monoclonal antibodies is the lack of a suitable myeloma cell line to be used for fusion experiments. In order to create fully human monoclonal antibodies for passive immunization, the human mouse heteromyeloma cell line CB-F7 was evaluated. Using this cell line, we generated human monoclonal antibodies against Bacillus anthracis toxin components. Antibodies against protective antigen (PA) and against lethal factor (LF) were obtained using peripheral blood lymphocytes (PBLs) from persons vaccinated with the UK anthrax vaccine. PBL were fused with the cell line CB-F7. We obtained several clones producing PA specific Ig and one clone (hLF1-SAN) producing a monoclonal antibody (hLF1) directed against LF. The LF binding antibody was able to neutralize Anthrax toxin activity in an in vitro neutralization assay, and preliminary in vivo studies in mice also indicated a trend towards protection. We mapped the epitope of the antibody binding to LF by dot blot analysis and ELIFA using 80 synthetic LF peptides of 20 amino acid lengths with an overlapping range of 10 amino acids. Our results suggest the binding of the monoclonal antibody to the peptide regions 121-150 or 451-470 of LF. The Fab-fragment of the antibody hLF1 was cloned in Escherichia coli and could be useful as part of a fully human monoclonal antibody for the treatment of Anthrax infections. In general, our studies show the applicability of the CB-F7 line to create fully human monoclonal antibodies for vaccination. Copyright © 2010 Elsevier GmbH. All rights reserved.

Chemical passivation as a method of improving the electrochemical corrosion resistance of Co-Cr-based dental alloy.

PubMed

Rylska, Dorota; Sokołowski, Grzegorz; Sokołowski, Jerzy; Łukomska-Szymańska, Monika

2017-01-01

The purpose of the study was to evaluate corrosion resistance of Wirobond C® alloy after chemical passivation treatment. The alloy surface undergone chemical passivation treatment in four different media. Corrosion studies were carried out by means of electrochemical methods in saline solution. Corrosion effects were determined using SEM. The greatest increase in the alloy polarization resistance was observed for passive layer produced in Na2SO4 solution with graphite. The same layer caused the highest increase in corrosion current. Generally speaking, the alloy passivation in Na2SO4 solution with graphite caused a substantial improvement of the corrosion resistance. The sample after passivation in Na2SO4 solution without graphite, contrary to others, lost its protective properties along with successive anodic polarization cycles. The alloy passivation in Na3PO4 solution with graphite was the only one that caused a decrease in the alloy corrosion properties. The SEM studies of all samples after chemical passivation revealed no pit corrosion - in contrast to the sample without any modification. Every successive polarization cycle in anodic direction of pure Wirobond C® alloy enhances corrosion resistance shifting corrosion potential in the positive direction and decreasing corrosion current value. The chemical passivation in solutions with low pH values decreases susceptibility to electrochemical corrosion of Co-Cr dental alloy. The best protection against corrosion was obtained after chemical passivation of Wirobond C® in Na2SO4 solution with graphite. Passivation with Na2SO4 in solution of high pH does not cause an increase in corrosion resistance of WIROBOND C. Passivation process increases alloy resistance to pit corrosion.

Hydrodynamic delivery of plasmid DNA encoding human FcγR-Ig dimers blocks immune-complex mediated inflammation in mice.

PubMed

Shashidharamurthy, R; Machiah, D; Bozeman, E N; Srivatsan, S; Patel, J; Cho, A; Jacob, J; Selvaraj, P

2012-09-01

Therapeutic use and function of recombinant molecules can be studied by the expression of foreign genes in mice. In this study, we have expressed human Fcγ receptor-Ig fusion molecules (FcγR-Igs) in mice by administering FcγR-Ig plasmid DNAs hydrodynamically and compared their effectiveness with purified molecules in blocking immune-complex (IC)-mediated inflammation in mice. The concentration of hydrodynamically expressed FcγR-Igs (CD16A(F)-Ig, CD32A(R)-Ig and CD32A(H)-Ig) reached a maximum of 130 μg ml(-1) of blood within 24 h after plasmid DNA administration. The in vivo half-life of FcγR-Igs was found to be 9-16 days and western blot analysis showed that the FcγR-Igs were expressed as a homodimer. The hydrodynamically expressed FcγR-Igs blocked 50-80% of IC-mediated inflammation up to 3 days in a reverse passive Arthus reaction model. Comparative analysis with purified molecules showed that hydrodynamically expressed FcγR-Igs are more efficient than purified molecules in blocking IC-mediated inflammation and had a higher half-life. In summary, these results suggest that the administration of a plasmid vector with the FcγR-Ig gene can be used to study the consequences of blocking IC binding to FcγRs during the development of inflammatory diseases. This approach may have potential therapeutic value in treating IC-mediated inflammatory autoimmune diseases such as lupus, arthritis and autoimmune vasculitis.

Epitope and isotype specificities of antibodies to β-amyloid peptide for protection against Alzheimer's disease-like neuropathology

PubMed Central

Bard, Frédérique; Barbour, Robin; Cannon, Catherine; Carretto, Robert; Fox, Michael; Games, Dora; Guido, Teresa; Hoenow, Kathleen; Hu, Kang; Johnson-Wood, Kelly; Khan, Karen; Kholodenko, Dora; Lee, Celeste; Lee, Mike; Motter, Ruth; Nguyen, Minh; Reed, Amanda; Schenk, Dale; Tang, Pearl; Vasquez, Nicki; Seubert, Peter; Yednock, Ted

2003-01-01

Transgenic PDAPP mice, which express a disease-linked isoform of the human amyloid precursor protein, exhibit CNS pathology that is similar to Alzheimer's disease. In an age-dependent fashion, the mice develop plaques containing β-amyloid peptide (Aβ) and exhibit neuronal dystrophy and synaptic loss. It has been shown in previous studies that pathology can be prevented and even reversed by immunization of the mice with the Aβ peptide. Similar protection could be achieved by passive administration of some but not all monoclonal antibodies against Aβ. In the current studies we sought to define the optimal antibody response for reducing neuropathology. Immune sera with reactivity against different Aβ epitopes and monoclonal antibodies with different isotypes were examined for efficacy both ex vivo and in vivo. The studies showed that: (i) of the purified or elicited antibodies tested, only antibodies against the N-terminal regions of Aβ were able to invoke plaque clearance; (ii) plaque binding correlated with a clearance response and neuronal protection, whereas the ability of antibodies to capture soluble Aβ was not necessarily correlated with efficacy; (iii) the isotype of the antibody dramatically influenced the degree of plaque clearance and neuronal protection; (iv) high affinity of the antibody for Fc receptors on microglial cells seemed more important than high affinity for Aβ itself; and (v) complement activation was not required for plaque clearance. These results indicate that antibody Fc-mediated plaque clearance is a highly efficient and effective process for protection against neuropathology in an animal model of Alzheimer's disease. PMID:12566568

Protection against rat vaginal candidiasis by adoptive transfer of vaginal B lymphocytes.

PubMed

De Bernardis, Flavia; Santoni, Giorgio; Boccanera, Maria; Lucciarini, Roberta; Arancia, Silvia; Sandini, Silvia; Amantini, Consuelo; Cassone, Antonio

2010-06-01

Vulvovaginal candidiasis is a mucosal infection affecting many women, but the immune mechanisms operating against Candida albicans at the mucosal level remain unknown. A rat model was employed to further characterize the contribution of B and T cells to anti-Candida vaginal protection. Particularly, the protective role of vaginal B cells was studied by means of adoptive transfer of vaginal CD3(-) CD5(+) IgM(+) cells from Candida-immunized rats to naïve animals. This passive transfer of B cells resulted into a number of vaginal C. albicans CFU approximately 50% lower than their controls. Sorted CD3(-) CD5(+) IgM(+) vaginal B lymphocytes from Candida-infected rats proliferated in response to stimulation with an immunodominant mannoprotein (MP) antigen of the fungus. Importantly, anti-MP antibodies and antibody-secreting B cells were detected in the supernatant and cell cultures, respectively, of vaginal B lymphocytes from infected rats incubated in vitro with vaginal T cells and stimulated with MP. No such specific antibodies were found when using vaginal B cells from uninfected rats. Furthermore, inflammatory and anti-inflammatory cytokines, such as interleukin-2 (IL-2), IL-6 and IL-10, were found in the supernatant of vaginal B cells from infected rats. These data are evidence of a partial anti-Candida protective role of CD3(-) CD5(+) IgM(+) vaginal B lymphocytes in our experimental model.

The epidemiological and serological characteristics of measles in Dongguan, China, 2005-2014.

PubMed

Han, Ke; Chen, Shaoli; Tang, Cuifei; Wen, Jinjun; Li, Jingquan; Ni, Jindong; Zheng, Xueli

2016-08-02

This study examined the epidemiological and serological characteristics of measles in Dongguan, China. From 2005 to 2014, a total of 8,224 measles cases were reported in Dongguan, 33.5% of which were aged <1 y and 30.6% >14 y. From 2005 to 2014, the proportion of the <1 y measles cases increased year by year from 24.3% to 47.9%. Of the cases aged ≥8 months (n = 6,768 cases), only 11.6% had been immunized with at least one dose of measles vaccine. Of the 2,213 cases who had never been immunized with measles vaccine, immigrants accounted for 82.4%. 52.4% of the measles cases were diagnosed with pneumonia, and 12 cases died from respiratory failure. Seroprevalence rate in women and their newborns was 86.0% and 82.5%, respectively. Measurement of serum measles antibody levels for infants aged less than 8 months indicated that seroprevalence rate dramatically declined from 97.3% at birth to 9.3% and 13.2% at 6- and 7- month old. The existence of a sufficient pool of unvaccinated people (especially immigrants) and decreased level of passively transferred measles antibodies in infants from vaccinated mothers contributed to the sustained transmission observed in Dongguan. In addition to high routine vaccination coverage, new strategies and innovations for measles vaccination are needed to eliminate measles.

The epidemiological and serological characteristics of measles in Dongguan, China, 2005–2014

PubMed Central

Han, Ke; Chen, Shaoli; Tang, Cuifei; Wen, Jinjun; Li, Jingquan; Ni, Jindong; Zheng, Xueli

2016-01-01

ABSTRACT This study examined the epidemiological and serological characteristics of measles in Dongguan, China. From 2005 to 2014, a total of 8,224 measles cases were reported in Dongguan, 33.5% of which were aged <1 y and 30.6% >14 y. From 2005 to 2014, the proportion of the <1 y measles cases increased year by year from 24.3% to 47.9%. Of the cases aged ≥8 months (n = 6,768 cases), only 11.6% had been immunized with at least one dose of measles vaccine. Of the 2,213 cases who had never been immunized with measles vaccine, immigrants accounted for 82.4%. 52.4% of the measles cases were diagnosed with pneumonia, and 12 cases died from respiratory failure. Seroprevalence rate in women and their newborns was 86.0% and 82.5%, respectively. Measurement of serum measles antibody levels for infants aged less than 8 months indicated that seroprevalence rate dramatically declined from 97.3% at birth to 9.3% and 13.2% at 6- and 7- month old. The existence of a sufficient pool of unvaccinated people (especially immigrants) and decreased level of passively transferred measles antibodies in infants from vaccinated mothers contributed to the sustained transmission observed in Dongguan. In addition to high routine vaccination coverage, new strategies and innovations for measles vaccination are needed to eliminate measles. PMID:27003239

Multi-disease analysis of maternal antibody decay using non-linear mixed models accounting for censoring.

PubMed

Goeyvaerts, Nele; Leuridan, Elke; Faes, Christel; Van Damme, Pierre; Hens, Niel

2015-09-10

Biomedical studies often generate repeated measures of multiple outcomes on a set of subjects. It may be of interest to develop a biologically intuitive model for the joint evolution of these outcomes while assessing inter-subject heterogeneity. Even though it is common for biological processes to entail non-linear relationships, examples of multivariate non-linear mixed models (MNMMs) are still fairly rare. We contribute to this area by jointly analyzing the maternal antibody decay for measles, mumps, rubella, and varicella, allowing for a different non-linear decay model for each infectious disease. We present a general modeling framework to analyze multivariate non-linear longitudinal profiles subject to censoring, by combining multivariate random effects, non-linear growth and Tobit regression. We explore the hypothesis of a common infant-specific mechanism underlying maternal immunity using a pairwise correlated random-effects approach and evaluating different correlation matrix structures. The implied marginal correlation between maternal antibody levels is estimated using simulations. The mean duration of passive immunity was less than 4 months for all diseases with substantial heterogeneity between infants. The maternal antibody levels against rubella and varicella were found to be positively correlated, while little to no correlation could be inferred for the other disease pairs. For some pairs, computational issues occurred with increasing correlation matrix complexity, which underlines the importance of further developing estimation methods for MNMMs. Copyright © 2015 John Wiley & Sons, Ltd.

Acute effects of high- and low-intensity exercise bouts on leukocyte counts.

PubMed

Neves, Pedro Rogério Da Silva; Tenório, Thiago Ricardo Dos Santos; Lins, Tatiana Acioli; Muniz, Maria Tereza Cartaxo; Pithon-Curi, Tânia Cristina; Botero, João Paulo; Do Prado, Wagner Luiz

2015-06-01

It is widely accepted that physical exercise may bring about changes in the immune system. Even acute bouts of exercise can alter the number and function of leukocytes, but the degree of white blood cell trafficking depends on the intensity and duration of exercise. The aim of this study was to analyze the acute and short-term effects of exercise intensity on leukocyte counts and leukocyte subsets. Nine physically healthy, active young males (21.0 ± 1.9 years) underwent three experimental trials: high exercise intensity [80% peak oxygen consumption (VO 2peak )], low exercise intensity (40% VO 2peak ), and the control condition (no exercise). Blood samples were collected prior to exercise, immediately after exercise, and 2 hours after exercise. Two-way analysis of variance for repeated measures was used to evaluate differences between the trials and the time-points, and to compare times within trials. There was a greater increase in the leukocyte count after high-intensity exercise, compared to the control condition ( p  < 0.01) and low-intensity exercise ( p  < 0.01). This effect was still present 2 hours after passive recovery ( p  < 0.01). When the same participants were submitted to different exercise intensities, the acute and short-term effects of exercise on white blood cells were intensity-dependent immediately after exercise (i.e., lymphocytosis and monocytosis) and 2 hours after passive recovery (i.e., neutrophilia).

Neutralizing Antibodies Induced by Gene-Based Hydrodynamic Injection Have a Therapeutic Effect in Lethal Influenza Infection

PubMed Central

Yamazaki, Tatsuya; Nagashima, Maria; Ninomiya, Daisuke; Ainai, Akira; Fujimoto, Akira; Ichimonji, Isao; Takagi, Hidekazu; Morita, Naoko; Murotani, Kenta; Hasegawa, Hideki; Chiba, Joe; Akashi-Takamura, Sachiko

2018-01-01

The influenza virus causes annual epidemics and occasional pandemics and is thus a major public health problem. Development of vaccines and antiviral drugs is essential for controlling influenza virus infection. We previously demonstrated the use of vectored immune-prophylaxis against influenza virus infection. We generated a plasmid encoding neutralizing IgG monoclonal antibodies (mAbs) against A/PR/8/34 influenza virus (IAV) hemagglutinin (HA). We then performed electroporation of the plasmid encoding neutralizing mAbs (EP) in mice muscles and succeeded in inducing the expression of neutralizing antibodies in mouse serum. This therapy has a prophylactic effect against lethal IAV infection in mice. In this study, we established a new method of passive immunotherapy after IAV infection. We performed hydrodynamic injection of the plasmid encoding neutralizing mAbs (HD) involving rapid injection of a large volume of plasmid-DNA solution into mice via the tail vein. HD could induce neutralizing antibodies in the serum and in several mucosal tissues more rapidly than in EP. We also showed that a single HD completely protected the mice even after infection with a lethal dose of IAV. We also established other isotypes of anti-HA antibody (IgA, IgM, IgD, and IgE) and showed that like anti-HA IgG, anti-HA IgA was also effective at combating upper respiratory tract IAV infection. Passive immunotherapy with HD could thus provide a new therapeutic strategy targeting influenza virus infection. PMID:29416543

Muscle damage and immune responses to prolonged exercise in environmental extreme conditions.

PubMed

Hassan, Emad S

2016-10-01

This study aimed to investigate the effect of prolonged exercise with and without a thermal clamp on leukocyte cell, stress hormones, cytokine and muscle damage responses. Fifteen healthy male volunteers (means±SD: age 22±3 yr; mass 75.8±3.2 kg; maximal oxygen uptake 55±7 mL/min/kg) randomly completed four chamber trials of 1 hour each, in different environment and separated by 7 days. Trials were: 1) exercise induced heating (EX-heating [EX-H]: temperature/humidity, 38° C/50%); 2) exercise with a thermal clamp (EX-cooling [EX-C]: temperature/humidity, 18° C/50%); 3) passive heating (PA-H: temperature/ humidity, 38° C/50%); 4) passive cooling (PA-C: temperature/ humidity, 18° C/50%). EX-H and EX-C were composed of 1h treadmill runs at 80% individual anaerobic threshold (IAT). Blood samples were collected at pre-post, and 1h postenvironments exposure. Compared to EX-H, exercise-induced increases in core temperature, heart rate, cortisol, human growth hormone (hGH)), Interleukin-6 (IL-6), leukocyte counts and creatine kinase (CK) and Myoglobin (Mb) were significantly (P<0.01) more pronounced than in EX-C. These results suggest that the additional impact of elevated ambient temperatures on stress responses to endurance exercise in trained subjects seems to affect primarily the hormonal systems and resulting changes in leukocyte number, creatine kinase, Myoglobin and interleukine-6.

Disease screening profiles and colostrum management practices on 16 Irish suckler beef farms.

PubMed

O'Shaughnessy, James; Earley, Bernadette; Barrett, Damien; Doherty, Michael L; Crosson, Paul; de Waal, Theo; Mee, John F

2015-01-01

Calf output is a key element in determining the profitability of a suckler beef enterprise. Infectious agents such as Bovine Virus Diarrhoea (BVD) virus, colostrum management and parasitic challenge can all affect calf output. Prior to the national BVD eradication programme, there was little published information on either the prevalence or effect of BVD in Irish beef herds. There is little published information on colostrum management practices in Irish commercial beef herds and there have also been few studies published on the prevalence of liver fluke or rumen fluke infection in Irish beef herds. Sixteen farms participating in the Teagasc/Farmers Journal BETTER farm beef programme were used in this study. Fourteen herds were screened for the presence of BVD virus in 2010 using RT-PCR. In 13 herds, blood samples were collected from calves (2-14 days of age) in November 2011 - April 2012 to determine their passive immune status using the zinc sulphate turbidity (ZST) test, while in 12 herds, blood and faecal samples were taken in order to determine the level of exposure to gastrointestinal and hepatic helminths. The overall prevalence of BVD virus-positive cattle was 0.98% (range 0 - 3% per herd, range 0.6 - 3.0% per positive herd). Eighteen of the 82 calves (22%) sampled had ZST values less than 20 units (herd mean range 17.0 - 38.5 units) indicating a failure of passive transfer. The overall animal-level (herd-level) prevalence of liver fluke and rumen fluke infection in these herds was 40.5% (100%) and 20.8% (75%), respectively. The potential costs associated with the presence of animals persistently infected with BVD virus through the increased use of antibiotics; the rate of failure of passive transfer of colostral immunoglobulins and the high prevalence of liver fluke infection in these herds highlight that some Irish suckler beef farms may not be realizing their economic potential due to a range of herd health issues. The use of farm-specific herd health plans should be further encouraged on Irish suckler beef farms.

Innovations in cold chain equipment for immunization supply chains.

PubMed

Robertson, Joanie; Franzel, Lauren; Maire, Denis

2017-04-19

Since 2010, numerous new technologies have entered the immunization cold chain equipment market. The World Health Organization (WHO) Immunization Devices Programme-Performance, Quality and Safety (PQS)-has played a key role in bringing these to market. In this article, the authors explore the emergence of new cold chain equipment technologies from 2004 to 2016 and the role of PQS in this evolution. This review focuses on three major vaccine cold chain technology innovations-solar direct-drive refrigerators, long-term passive cold boxes, and equipment with user-independent freeze prevention. For the review, we used online data from WHO PQS, a literature search, and unpublished research reports. Timelines with key milestones in the emergence of the three focus technologies show delays of between one and three years between earliest field trials and publication of WHO specifications; procurement builds after the WHO prequalification of initial devices. The timelines show the role of PQS as both gatekeeper and enabler for cold chain equipment technologies. The use of target product profiles by PQS has increased its ability to signal preferred attributes and to engage with manufacturers during the product-development stage. Procurement data show how demand for solar direct-drive refrigerators increased over time. Gavi, the Vaccine Alliance, is employing demand-generation strategies to try to drive procurement of technologies with favorable technical attributes. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Advanced medical countermeasures for radiological accidents and nuclear disasters: prevention, prophylaxis, treatment and pre- and post-exposure management.

NASA Astrophysics Data System (ADS)

Popov, Dmitri; Maliev, Slava; Jones, Jeffrey

Countermeasures against nuclear terrorism to prevent or limit the number of irradiated human population or radiation intoxications include early identification of the nuclear terrorism event and all persons which exposed by radiation, decontamination program and procedures, radiation control, and medical countermeasures which include medical diagnosis,differential diagnosis of Acute Radiation Syndromes by Immune Enzyme Assay , pre-exposure vaccination with Human Antiradiation Vaccine, post-exposure specific treatment - de-intoxication with Radiation Antidote IgG (blocking Antiradiation Antibodies). Our Advanced Medical Technology elaborated as a part of effective countermeasure include Plan of Action.Countermeasures against nuclear terrorism to prevent or limit the number of high level of lethality and severe forms of radiation illness or intoxications include A.early identification of the nuclear terrorism event and persons exposed,b. appropriate decontamination, c. radiation control, and d.medical countermeasures and medical management of ARS. Medical countermeasures, which include medical interventions such as active immuneprophylaxis with Human Antiradiation Vaccine , passive immune-prophylaxis with Antiradiation Antitoxins immune-globulins IgG , and chemoprophylaxis - post-exposure antioxidants prophylaxis and antibioticprophylaxis. Medical countermeasures with Antiradiation Vaccine should be initiated before an exposure (if individuals are identified as being at high risk for exposure)but after a confirmed exposure event Antiradiation Vaccine not effective and Antiradiation Antidot IgG must be applyed for treatment of Acute Radiation Syndromes.

Vaccination of lambs against Taenia ovis infection using antigens collected during in vitro cultivation of larvae: passive protection via colostrum from vaccinated ewes and the duration of immunity from a single vaccination.

PubMed

Rickard, M D; Boddington, E B; McQuade, N

1977-11-01

Fifty Merino-cross ewes were vaccinated approximately four weeks before parturition with antigens collected during in vitro cultivation of Taenia ovis larvae. A further 50 pregnant ewes were sham-vaccinated at the same time. When the first 20 lambs from each group of ewes were one to two weeks old they were placed, with the ewes, on an experimental paddock heavily contaminated with T ovis eggs. After six weeks the lambs were killed and their total carcase musculature and hearts examined for cysticerci. The results showed that the ewes vaccinated in late pregnancy had conferred a very high degree of transcolostral immunity upon their lambs against the T ovis challenge infection. Eighty T ovis-free Merino-cross weaner lambs, four months old, were divided into two groups of 40. One group was vaccinated with T ovis culture antigens and the other group was sham-vaccinated. At intervals of one, four, eight and 12 months after vaccination 10 lambs from each group were allowed to graze on the plot contaminated with T ovis eggs. After six weeks the lambs were killed and examined for cysticerci of T ovis. The results indicated that the single vaccination had stimulated a high level of immunity which persisted for at least 12 months.

Theories of otitis media pathogenesis, with a focus on Indigenous children.

PubMed

Wiertsema, Selma P; Leach, Amanda J

2009-11-02

Otitis media is a common childhood illness associated with hearing loss, social disadvantage and medical costs. Prevalence and severity are high among Indigenous children. Respiratory bacterial and viral pathogens ascend the eustachian tube from the nasopharynx to the middle ear, causing inflammation, fluid accumulation, and bulging of the tympanic membrane, with or without pain. Among Australian Indigenous children, ear disease commences earlier in life, and involves multiple strains of bacterial pathogens at high density that persist longer. Persistent nasal discharge, overcrowded living conditions (particularly exposure to many children) and poor facilities for washing children perpetuate a vicious cycle of transmission and infection. Risk factors include environmental tobacco smoke, season, lack of breastfeeding, younger age and immature immune system, and possibly genetic factors. The innate immune system is a critical first response to infection, particularly as passive maternal antibodies decline and during the maturation of the infant adaptive immune response. The relative contributions of innate factors to protection from otitis media are currently not well understood. A diversity of antibodies that target strain-specific and conserved antigens are generated in response to natural exposure to otitis media pathogens (or to vaccines). Deficiencies in these antibodies may explain susceptibility to recurrent infections. Incremental contributions from all these elements are likely to be important in otitis media susceptibility versus protection. Effective medical and social strategies to prevent early age of onset are urgently needed.

Role of neutralizing antibodies and T-cells in pathogenesis of herpes simplex virus infection in congenitally athymic mice.

PubMed

Kapoor, A K; Buckmaster, A; Nash, A A; Field, H J; Wildy, P

1982-11-01

Congenitally athymic nude mice were infected with 10(4) p.f.u. herpes simplex type 1 (strain SC16). Following the passive transfer of neutralizing monoclonal antibodies (AP7, AP8 and AP12) it was observed that AP7 alone reduced the virus infectivity in the nervous system; AP8 and AP12 failed to protect mice probably due to poor in vivo binding to the neutralization site on the virus. Latent ganglionic infection could be established in nude mice following adoptive transfer of optimum number (2 x 10(7) cells/mouse) of immune lymph node cells from day 7 herpes virus-infected hairy immunocompetent donor mice. Moreover, in some of the immune lymph node cell protected nudes, latency could be maintained even in complete absence of neutralizing antibodies. Results of ear-ablation experiments revealed that removal of primary source of infection after day 5 of infection reduced the amount of virus in the ganglia and spinal cord. Acute neurological infection was not detected following transfer of protective anti-gp-D neutralizing antibody (LP2) in combination with removal of infected pinna. These data suggest that continuous seeding of virus occurs in related ganglia via the axonal route from infected ear pinna. It appears that local T-cell-mediated immune mechanisms are involved in maintenance of latency.

Noise-immune cavity-enhanced optical frequency comb spectroscopy: a sensitive technique for high-resolution broadband molecular detection

NASA Astrophysics Data System (ADS)

Khodabakhsh, Amir; Johansson, Alexandra C.; Foltynowicz, Aleksandra

2015-04-01

Noise-immune cavity-enhanced optical frequency comb spectroscopy (NICE-OFCS) is a recently developed technique that utilizes phase modulation to obtain immunity to frequency-to-amplitude noise conversion by the cavity modes and yields high absorption sensitivity over a broad spectral range. We describe the principles of the technique and discuss possible comb-cavity matching solutions. We present a theoretical description of NICE-OFCS signals detected with a Fourier transform spectrometer (FTS) and validate the model by comparing it to experimental CO2 spectra around 1,575 nm. Our system is based on an Er:fiber femtosecond laser locked to a cavity and phase-modulated at a frequency equal to a multiple of the cavity free spectral range (FSR). The NICE-OFCS signal is detected by a fast-scanning FTS equipped with a high-bandwidth commercial detector. We demonstrate a simple method of passive locking of the modulation frequency to the cavity FSR that significantly improves the long-term stability of the system, allowing averaging times on the order of minutes. Using a cavity with a finesse of ~9,000, we obtain absorption sensitivity of 6.4 × 10-11 cm-1 Hz-1/2 per spectral element and concentration detection limit for CO2 of 450 ppb Hz-1/2, determined by multiline fitting.

Self-immunity microcapsules for corrosion protection of steel bar in reinforced concrete

NASA Astrophysics Data System (ADS)

Wang, Yanshuai; Fang, Guohao; Ding, Weijian; Han, Ningxu; Xing, Feng; Dong, Biqin

2015-12-01

A novel microcapsule-based self-immunity system for reinforced concrete is proposed. Its feasibility for hindering the corrosion of steel rebar by means of lifting the threshold value of [Cl-]/[OH-] is discussed. Precisely controlled release behavior enables corrosion protection in the case of depassivation. The release process is characterized over a designated range of pH values, and its release characteristics of the microcapsules, triggered by decreasing pH value, are captured by observing that the core crystals are released when exposed to a signal (stimulus). The aim of corrosion protection of steel bar is achieved through the constantly-stabilized passive film, and its stability is promoted using continuous calcium hydroxide released from the microcapsule, restoring alkaline conditions. The test results exhibited that the release process of the microcapsules is a function of time. Moreover, the release rate of core materials could interact with environmental pH value, in which the release rate is found to increase remarkably with decreasing pH value, but is inhibited by high pH levels.

Self-immunity microcapsules for corrosion protection of steel bar in reinforced concrete.

PubMed

Wang, Yanshuai; Fang, Guohao; Ding, Weijian; Han, Ningxu; Xing, Feng; Dong, Biqin

2015-12-17

A novel microcapsule-based self-immunity system for reinforced concrete is proposed. Its feasibility for hindering the corrosion of steel rebar by means of lifting the threshold value of [Cl(-)]/[OH(-)] is discussed. Precisely controlled release behavior enables corrosion protection in the case of depassivation. The release process is characterized over a designated range of pH values, and its release characteristics of the microcapsules, triggered by decreasing pH value, are captured by observing that the core crystals are released when exposed to a signal (stimulus). The aim of corrosion protection of steel bar is achieved through the constantly-stabilized passive film, and its stability is promoted using continuous calcium hydroxide released from the microcapsule, restoring alkaline conditions. The test results exhibited that the release process of the microcapsules is a function of time. Moreover, the release rate of core materials could interact with environmental pH value, in which the release rate is found to increase remarkably with decreasing pH value, but is inhibited by high pH levels.

Antibody binding of circulating ergot alkaloids in cattle grazing tall fescue.

PubMed

Hill, N S; Thompson, F N; Dawe, D L; Stuedemann, J A

1994-03-01

Direct evidence linking alkaloids found in endophyte-infected tall fescue forage with the livestock disorder known as fescue toxicosis is lacking. Physiologic effects of fescue toxicosis include reduced serum prolactin concentration in cattle. A monoclonal antibody specific to the lysergic moiety of ergot alkaloids was developed in mice after creating an immunogen by linking lysergol to human serum albumin. The antibody was specific to the lysergic moiety and, therefore, it cross-reacted with ergot alkaloids, lysergic acid, and lysergol. The antibody did not cross-react with alkaloid derivatives that had bromated or hydrogenated lysergic ring moieties. Fescue toxicosis conditions were elicited in yearling Angus steers by permitting them to graze endophyte-infected tall fescue containing > 650 micrograms/kg of ergovaline for 60 days. Passive immunization of steers by infusion of the monoclonal antibody increased serum prolactin concentration by 7 ng/ml, beginning immediately after infusion. Control steers did not respond to treatment with bovine serum albumin. Active immunization of yearling Angus heifers with immunogens containing lysergol or ergonovine linked to human serum albumin resulted in an antibody response.

Phagocytic cells contribute to the antibody-mediated elimination of pulmonary-infected SARS coronavirus.

PubMed

Yasui, Fumihiko; Kohara, Michinori; Kitabatake, Masahiro; Nishiwaki, Tetsu; Fujii, Hideki; Tateno, Chise; Yoneda, Misako; Morita, Kouichi; Matsushima, Kouji; Koyasu, Shigeo; Kai, Chieko

2014-04-01

While the 2002-2003 outbreak of severe acute respiratory syndrome (SARS) resulted in 774 deaths, patients who were affected with mild pulmonary symptoms successfully recovered. The objective of the present work was to identify, using SARS coronavirus (SARS-CoV) mouse infection models, immune factors responsible for clearing of the virus. The elimination of pulmonary SARS-CoV infection required the activation of B cells by CD4(+) T cells. Furthermore, passive immunization (post-infection) with homologous (murine) anti-SARS-CoV antiserum showed greater elimination efficacy against SARS-CoV than that with heterologous (rabbit) antiserum, despite the use of equivalent titers of neutralizing antibodies. This distinction was mediated by mouse phagocytic cells (monocyte-derived infiltrating macrophages and partially alveolar macrophages, but not neutrophils), as demonstrated both by adoptive transfer from donors and by immunological depletion of selected cell types. These results indicate that the cooperation of anti-SARS-CoV antibodies and phagocytic cells plays an important role in the elimination of SARS-CoV. Copyright © 2014 Elsevier Inc. All rights reserved.

Protective immunity and lack of histopathological damage two years after DNA vaccination against infectious hematopoietic necrosis virus in trout

USGS Publications Warehouse

Kurath, Gael; Garver, Kyle A.; Corbeil, Serge; Elliott, Diane G.; Anderson, Eric D.; LaPatra, Scott E.

2006-01-01

The DNA vaccine pIHNw-G encodes the glycoprotein of the fish rhabdovirus infectious hematopoietic necrosis virus (IHNV). Vaccine performance in rainbow trout was measured 3, 6, 13, 24, and 25 months after vaccination. At three months all fish vaccinated with 0.1 μg pIHNw-G had detectable neutralizing antibody (NAb) and they were completely protected from lethal IHNV challenge with a relative percent survival (RPS) of 100% compared to control fish. Viral challenges at 6, 13, 24, and 25 months post-vaccination showed protection with RPS values of 47–69%, while NAb seroprevalence declined to undetectable levels. Passive transfer experiments with sera from fish after two years post-vaccination were inconsistent but significant protection was observed in some cases. The long-term duration of protection observed here defined a third temporal phase in the immune response to IHNV DNA vaccination, characterized by reduced but significant levels of protection, and decline or absence of detectable NAb titers. Examination of multiple tissues showed an absence of detectable long-term histopathological damage due to DNA vaccination.

Decreased total antioxidant capacity and increased oxidative stress in passive smoker infants and their mothers.

PubMed

Aycicek, Ali; Erel, Ozcan; Kocyigit, Abdurrahim

2005-12-01

Smoking has many adverse health effects in infants and adults. The purpose of the study was to study the effect of passive cigarette smoking on oxidative and antioxidative status of plasma in passive smoker infants and their mothers and to compare with those of non-smokers. Subjects were randomly chosen from infants aged 8-26 weeks and their mothers aged 20-34 years. Passive smoker infants (n = 29) and their mothers (n = 29) were defined as having other family members who smoked six or more cigarettes per day continually for at least 8 weeks. Non-smokers were defined as infants (n = 30) and their mothers (n = 24) who had never been exposed to passive smoking. The antioxidative status of plasma were perused by measuring the total antioxidant capacity. Oxidative status was evaluated by predicating total peroxide level, oxidative stress index, protein oxidation and lipid peroxidation. Plasma concentrations of total antioxidant capacity were significantly lower in passive smoker infants and their mothers than non-passive smoker infants and their mothers. However, lipid peroxidation and oxidative stress index were remarkably higher in passive smoker infants and their mothers than those of non-passive smoker infants and their mothers. There were significant correlations between the oxidative and antioxidative parameters of the passive smoker infants and their mothers. Oxidants are increased and antioxidants are decreased in passive smoker infants and their mothers than those of non-smokers. Passive smoker infants and their mothers are exposed to potent oxidative stress.

Passive lumbar tissue loading during trunk bending at three speeds: An in vivo study.

PubMed

Ning, Xiaopeng; Nussbaum, Maury A

2015-08-01

Low back disorders are closely related with the magnitude of mechanical loading on human spine. However, spinal loading contributed by the lumbar passive tissues is still not well understood. In this study, the effect of motion speed on lumbar passive moment output was investigated. In addition, the increase of lumbar passive moment during trunk bending was modeled. Twelve volunteers performed trunk-bending motions at three different speeds. Trunk kinematics and muscle activities were collected and used to estimate instantaneous spinal loading and the corresponding lumbar passive moment. The lumbar passive moments at different ranges of trunk motion were compared at different speed levels and the relationship between lumbar passive moment lumbar flexion was modeled. A non-linear, two-stage pattern of increase in lumbar passive moment was evident during trunk flexion. However, the effect of motion speed was not significant on lumbar passive moments or any of the model parameters. As reported previously, distinct lumbar ligaments may begin to generate tension at differing extents of trunk flexion, and this could be the cause of the observed two-stage increasing pattern of lumbar passive moment. The current results also suggest that changes in tissue strain rate may not have a significant impact on the total passive moment output at the relatively slow trunk motions examined here. Copyright © 2015 Elsevier Ltd. All rights reserved.

Anti-allergic activity of 2,4,6-trihydroxy-3-geranylacetophenone (tHGA) via attenuation of IgE-mediated mast cell activation and inhibition of passive systemic anaphylaxis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tan, Ji Wei; Israf, Daud Ahmad; Harith, Hanis Haze

tHGA, a geranyl acetophenone compound originally isolated from a local shrub called Melicope ptelefolia, has been previously reported to prevent ovalbumin-induced allergic airway inflammation in a murine model of allergic asthma by targeting cysteinyl leukotriene synthesis. Mast cells are immune effector cells involved in the pathogenesis of allergic diseases including asthma by releasing cysteinyl leukotrienes. The anti-asthmatic properties of tHGA could be attributed to its inhibitory effect on mast cell degranulation. As mast cell degranulation is an important event in allergic responses, this study aimed to investigate the anti-allergic effects of tHGA in cellular and animal models of IgE-mediated mastmore » cell degranulation. For in vitro model of IgE-mediated mast cell degranulation, DNP-IgE-sensitized RBL-2H3 cells were pre-treated with tHGA before challenged with DNP-BSA to induce degranulation. For IgE-mediated passive systemic anaphylaxis, Sprague Dawley rats were sensitized by intraperitoneal injection of DNP-IgE before challenged with DNP-BSA. Both in vitro and in vivo models showed that tHGA significantly inhibited the release of preformed mediators (β-hexosaminidase and histamine) as well as de novo mediators (interleukin-4, tumour necrosis factor-α, prostaglandin D{sub 2} and leukotriene C{sub 4}). Pre-treatment of tHGA also prevented IgE-challenged RBL-2H3 cells and peritoneal mast cells from undergoing morphological changes associated with mast cell degranulation. These findings indicate that tHGA possesses potent anti-allergic activity via attenuation of IgE-mediated mast cell degranulation and inhibition of IgE-mediated passive systemic anaphylaxis. Thus, tHGA may have the potential to be developed as a mast cell stabilizer for the treatment of allergic diseases in the future. - Highlights: • The in vitro and in vivo mast cell stabilizing effects of tHGA were examined. • tHGA counteracts the plasma membrane deformation in degranulating mast cells. • tHGA attenuates preformed and de novo mediators released by degranulating mast cells. • tHGA prevents in vivo mast cell activation and passive systemic anaphylaxis in rats. • tHGA could be a potential mast cell stabilizer for the treatment of allergic diseases.« less

Active and passive fatigue in simulated driving: discriminating styles of workload regulation and their safety impacts.

PubMed

Saxby, Dyani J; Matthews, Gerald; Warm, Joel S; Hitchcock, Edward M; Neubauer, Catherine

2013-12-01

Despite the known dangers of driver fatigue, it is a difficult construct to study empirically. Different forms of task-induced fatigue may differ in their effects on driver performance and safety. Desmond and Hancock (2001) defined active and passive fatigue states that reflect different styles of workload regulation. In 2 driving simulator studies we investigated the multidimensional subjective states and safety outcomes associated with active and passive fatigue. Wind gusts were used to induce active fatigue, and full vehicle automation to induce passive fatigue. Drive duration was independently manipulated to track the development of fatigue states over time. Participants were undergraduate students. Study 1 (N = 108) focused on subjective response and associated cognitive stress processes, while Study 2 (N = 168) tested fatigue effects on vehicle control and alertness. In both studies the 2 fatigue manipulations produced different patterns of subjective response reflecting different styles of workload regulation, appraisal, and coping. Active fatigue was associated with distress, overload, and heightened coping efforts, whereas passive fatigue corresponded to large-magnitude declines in task engagement, cognitive underload, and reduced challenge appraisal. Study 2 showed that only passive fatigue reduced alertness, operationalized as speed of braking and steering responses to an emergency event. Passive fatigue also increased crash probability, but did not affect a measure of vehicle control. Findings support theories that see fatigue as an outcome of strategies for managing workload. The distinction between active and passive fatigue is important for assessment of fatigue and for evaluating automated driving systems which may induce dangerous levels of passive fatigue. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Active–passive soil moisture retrievals during the SMAP validation experiment 2012

USDA-ARS?s Scientific Manuscript database

The goal of this study is to assess the performance of the active–passive algorithm for the NASA Soil Moisture Active Passive mission (SMAP) using airborne and ground observations from a field campaign. The SMAP active–passive algorithm disaggregates the coarse-resolution radiometer brightness tempe...

Interlanguage Passive Construction

ERIC Educational Resources Information Center

Simargool, Nirada

2008-01-01

Because the appearance of the passive construction varies cross linguistically, differences exist in the interlanguage (IL) passives attempted by learners of English. One such difference is the widely studied IL pseudo passive, as in "*new cars must keep inside" produced by Chinese speakers. The belief that this is a reflection of L1 language…

Print media coverage of research on passive smoking

PubMed Central

Kennedy, G.; Bero, L.

1999-01-01

OBJECTIVE—To assess the extent and content of newspaper and magazine coverage of research on passive smoking.
DESIGN—Content analysis of newspaper and magazine articles.
SUBJECTS—Articles reporting on passive smoking research published in newspapers (n = 180) or magazines (n = 92) between January 1981 and December 1994.
MAIN OUTCOME MEASURES—Numbers of articles, conclusions of articles, sources quoted, numbers and characteristics of research studies cited, presence of tobacco advertising.
RESULTS—The number of newspaper and magazine articles reporting on passive smoking research increased from four in 1981 to 57 in 1992 and 32 in 1994. Sixty-two per cent (168/272) of articles concluded that the research on passive smoking is controversial. Tobacco industry representatives were quoted significantly more often in newspaper articles (52%, 94/180) than magazine articles (12%, 11/92) (p<0.0001). Of 121 different research studies cited in the lay press articles, only 15 were from tobacco-industry sponsored projects or publications. In magazines, acceptance of tobacco industry advertising was associated with the conclusion that research on passive smoking is controversial (p<0.0001).
CONCLUSIONS—Although research on the harmful effects of passive smoking accumulated between 1981 and 1994, lay press coverage of the research maintained that the science was controversial. Few research studies were cited to support the industry's claim that passive smoking is not harmful to health. However, tobacco industry representatives who were critical of the research methods used to study the health effects of passive smoking were frequently quoted.


Keywords: environmental tobacco smoke; media; passive smoking PMID:10599568

Tissue resident macrophages are sufficient for demyelination during peripheral nerve myelin induced experimental autoimmune neuritis?

PubMed

Taylor, Jude Matthew

2017-12-15

The contribution of resident endoneurial tissue macrophages versus recruited monocyte derived macrophages to demyelination and disease during Experimental Autoimmune Neuritis (EAN) was investigated using passive transfer of peripheral nerve myelin (PNM) specific serum antibodies or adoptive co-transfer of PNM specific T and B cells from EAN donors to leukopenic and normal hosts. Passive transfer of PNM specific serum antibodies or adoptive co-transfer of myelin specific T and B cells into leukopenic recipients resulted in a moderate reduction in nerve conduction block or in the disease severity compared to the normal recipients. This was despite at least a 95% decrease in the number of circulating mononuclear cells during the development of nerve conduction block and disease and a 50% reduction in the number of infiltrating endoneurial macrophages in the nerve lesions of the leukopenic recipients. These observations suggest that during EAN in Lewis rats actively induced by immunization with peripheral nerve myelin, phagocytic macrophages originating from the resident endoneurial population may be sufficient to engage in demyelination initiated by anti-myelin antibodies in this model. Copyright © 2017 Elsevier B.V. All rights reserved.

The influence of macrophages on mesenchymal stromal cell therapy: passive or aggressive agents?

PubMed Central

Carty, F.; English, K.

2017-01-01

Summary Mesenchymal stromal cells (MSC) have emerged as promising cell therapies for multiple conditions based on demonstrations of their potent immunomodulatory and regenerative capacities in models of inflammatory disease. Understanding the effects of MSC on T cells has dominated the majority of work carried out in this field to date; recently, however, a number of studies have shown that the therapeutic effect of MSC requires the presence of macrophages. It is timely to review the mechanisms and manner by which MSC modulate macrophage populations in order to design more effective MSC therapies and clinical studies. A complex cross‐talk exists through which MSC and macrophages communicate, a communication that is not controlled exclusively by MSC. Here, we examine the evidence that suggests that MSC not only respond to inflammatory macrophages and adjust their secretome accordingly, but also that macrophages respond to encounters with MSC, creating a feedback loop which contributes to the immune regulation observed following MSC therapy. Future studies examining the effects of MSC on macrophages should consider the antagonistic role that macrophages play in this exchange. PMID:28108980

Passive wall cooling panel with phase change material as a cooling agent

NASA Astrophysics Data System (ADS)

Majid, Masni A.; Tajudin, Rasyidah Ahmad; Salleh, Norhafizah; Hamid, Noor Azlina Abd

2017-11-01

The study was carried out to the determine performance of passive wall cooling panels by using Phase Change Materials as a cooling agent. This passive cooling system used cooling agent as natural energy storage without using any HVAC system. Eight full scale passive wall cooling panels were developed with the size 1500 mm (L) × 500 mm (W) × 100 mm (T). The cooling agent such as glycerine were filled in the tube with horizontal and vertical arrangement. The passive wall cooling panels were casting by using foamed concrete with density between 1200 kg/m3 - 1500 kg/m3. The passive wall cooling panels were tested in a small house and the differences of indoor and outdoor temperature was recorded. Passive wall cooling panels with glycerine as cooling agent in vertical arrangement showed the best performance with dropped of indoor air temperature within 3°C compared to outdoor air temperature. The lowest indoor air temperature recorded was 25°C from passive wall cooling panels with glycerine in vertical arrangement. From this study, the passive wall cooling system could be applied as it was environmental friendly and less maintenance.

Adsorption of molecular additive onto lead halide perovskite surfaces: A computational study on Lewis base thiophene additive passivation

NASA Astrophysics Data System (ADS)

Zhang, Lei; Yu, Fengxi; Chen, Lihong; Li, Jingfa

2018-06-01

Organic additives, such as the Lewis base thiophene, have been successfully applied to passivate halide perovskite surfaces, improving the stability and properties of perovskite devices based on CH3NH3PbI3. Yet, the detailed nanostructure of the perovskite surface passivated by additives and the mechanisms of such passivation are not well understood. This study presents a nanoscopic view on the interfacial structure of an additive/perovskite interface, consisting of a Lewis base thiophene molecular additive and a lead halide perovskite surface substrate, providing insights on the mechanisms that molecular additives can passivate the halide perovskite surfaces and enhance the perovskite-based device performance. Molecular dynamics study on the interactions between water molecules and the perovskite surfaces passivated by the investigated additive reveal the effectiveness of employing the molecular additives to improve the stability of the halide perovskite materials. The additive/perovskite surface system is further probed via molecular engineering the perovskite surfaces. This study reveals the nanoscopic structure-property relationships of the halide perovskite surface passivated by molecular additives, which helps the fundamental understanding of the surface/interface engineering strategies for the development of halide perovskite based devices.

Immunological unresponsiveness in mice. II. Cellular basis of immunological unresponsiveness induced in foetal and neonatal mice by transfer of human gamma-globulin by the maternal route.

PubMed Central

Shinka, S; Komatsu, T; Dohi, Y; Amano, T

1979-01-01

The cellular basis of the mechanism of immunological tolerance to human gamma-globulin (H gamma G) induced in foetal and neonatal mice by materno-foetal or materno-neonatal transfer after a single injection of tolerogen (deaggregated H gamma G) into the mothers was investigated using a cell transfer system and assays of passive haemagglutinating antibodies and plaque-forming cells to H gamma G. The results demonstrated that B cells are mainly involved in the tolerance induced on the fourteenth day of gestation, whereas inactivation of T cells may account for the tolerance induced on the eighteenth day of gestation and in the neonatal stage. Treatment of the mothers with tolerogen and then anti-H gamma G serum reduced the tolerance induced on the fourteenth day of gestation, but did not affect that induced on the eighteenth day of gestation and in the neonatal stage. Cell transfer experiments showed that B-cell tolerance induced on the fourteenth day of gestation was prevented by passive antibody, while T-cell tolerance induced on the eighteenth day of gestation and in the neonatal stage was not affected by passive antibody. Assay of the anti-DNP antibody response after immunization with DNP10-H gamma G showed that treatment of mice with the tolerogen on the eighteenth day of gestation, but not the fourteenth day of gestation, inactivated H gamma G-reactive helper cells. The significance of these results is discussed in relation to the results of the cell transfer experiments described as above. PMID:89080

THE IMPACT OF PASSIVE SAMPLING METHODOLOGIES USED IN THE DEARS

EPA Science Inventory

This abstract details the use of passive sampling methodologies in the Detroit Exposure and Aerosol Research Study (DEARS). A discussion about the utility of various gas-phase passive samplers used in the study will be described along with examples of field data measurements empl...

Vaccine candidate discovery for the next generation of malaria vaccines.

PubMed

Tuju, James; Kamuyu, Gathoni; Murungi, Linda M; Osier, Faith H A

2017-10-01

Although epidemiological observations, IgG passive transfer studies and experimental infections in humans all support the feasibility of developing highly effective malaria vaccines, the precise antigens that induce protective immunity remain uncertain. Here, we review the methodologies applied to vaccine candidate discovery for Plasmodium falciparum malaria from the pre- to post-genomic era. Probing of genomic and cDNA libraries with antibodies of defined specificities or functional activity predominated the former, whereas reverse vaccinology encompassing high throughput in silico analyses of genomic, transcriptomic or proteomic parasite data sets is the mainstay of the latter. Antibody-guided vaccine design spanned both eras but currently benefits from technological advances facilitating high-throughput screening and downstream applications. We make the case that although we have exponentially increased our ability to identify numerous potential vaccine candidates in a relatively short space of time, a significant bottleneck remains in their validation and prioritization for evaluation in clinical trials. Longitudinal cohort studies provide supportive evidence but results are often conflicting between studies. Demonstration of antigen-specific antibody function is valuable but the relative importance of one mechanism over another with regards to protection remains undetermined. Animal models offer useful insights but may not accurately reflect human disease. Challenge studies in humans are preferable but prohibitively expensive. In the absence of reliable correlates of protection, suitable animal models or a better understanding of the mechanisms underlying protective immunity in humans, vaccine candidate discovery per se may not be sufficient to provide the paradigm shift necessary to develop the next generation of highly effective subunit malaria vaccines. © 2017 The Authors. Immunology Published by John Wiley & Sons Ltd.

Is immunotherapy an opportunity for effective treatment of drug addiction?

PubMed

Zalewska-Kaszubska, Jadwiga

2015-11-27

Immunotherapy has a great potential of becoming a new therapeutic strategy in the treatment of addiction to psychoactive drugs. It may be used to treat addiction but also to prevent neurotoxic complications of drug overdose. In preclinical studies two immunological methods have been tested; active immunization, which relies on the administration of vaccines and passive immunization, which relies on the administration of monoclonal antibodies. Until now researchers have succeeded in developing vaccines and/or antibodies against addiction to heroin, cocaine, methamphetamine, nicotine and phencyclidine. Their effectiveness has been confirmed in preclinical studies. At present, clinical studies are being conducted for vaccines against nicotine and cocaine and also anti-methamphetamine monoclonal antibody. These preclinical and clinical studies suggest that immunotherapy may be useful in the treatment of addiction and drug overdose. However, there are a few problems to be solved. One of them is controlling the level of antibodies due to variability between subjects. But even obtaining a suitable antibody titer does not guarantee the effectiveness of the vaccine. Additionally, there is a risk of intentional or unintentional overdose. As vaccines prevent passing of drugs through the blood/brain barrier and thereby prevent their positive reinforcement, some addicted patients may erroneously seek higher doses of psychoactive substances to get "high". Consequently, vaccination should be targeted at persons who have a strong motivation to free themselves from drug dependency. It seems that immunotherapy may be an opportunity for effective treatment of drug addiction if directed to adequate candidates for treatment. For other addicts, immunotherapy may be a very important element supporting psycho- and pharmacotherapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Silicon surface passivation by silicon nitride deposition

NASA Technical Reports Server (NTRS)

Olsen, L. C.

1984-01-01

Silicon nitride deposition was studied as a method of passivation for silicon solar cell surfaces. The following three objectives were the thrust of the research: (1) the use of pecvd silicon nitride for passivation of silicon surfaces; (2) measurement techniques for surface recombination velocity; and (3) the importance of surface passivation to high efficiency solar cells.

Development of Verbal Passive in Williams Syndrome

ERIC Educational Resources Information Center

Perovic, Alexandra; Wexler, Kenneth

2010-01-01

Purpose: To experimentally investigate knowledge of passives of actional ("hold") and psychological ("love") verbs in children with Williams syndrome (WS). Passives are usually reported to be in line with mental age in WS. However, studies usually focus on passives of actional verbs only. Method: Twenty-six children with WS, ages 6-16, and 3…