Reduced efficacy of hemorrhagic enteritis virus vaccine in turkeys exposed to avian pneumovirus.

PubMed

Chary, Parag; Rautenschlein, Silke; Sharma, Jagdev M

2002-01-01

Avian pneumovirus (APV) is an immunosuppressive respiratory pathogen of turkeys. We examined the effect of APV infection on the vaccine efficacy of hemorrhagic enteritis virus (HEV) vaccines. APV was inoculated in 2-wk-old turkeys. Two or four days later, an attenuated HEV vaccine (HEVp30) or marble spleen disease virus (MSDV) vaccine were administered. Virulent HEV challenge was given 19 days after HEV vaccination. APV exposure compromised the ability of HEVp30 and MSDV to protect turkeys against virulent HEV. The protective index values were as follows: MSDV (100%) versus APV + MSDV (0%) (P < 0.05); HEVp30 (60%) versus APV + HEVp30 (30%) (P < 0.05) (Experiment I) and HEVp30 (56%) versus APV + HEVp30 (20%) (P < 0.05) (Experiment II). These data indicated that APV reduced the efficacy of HEV vaccines in turkeys.

Investigating the Use of an Enterotropic Newcastle Disease Virus as a Recombinant Vaccine Platform Targeting Poultry Enteric Viruses

USDA-ARS?s Scientific Manuscript database

Control strategies for poultry viral enteric disease must include vaccine platforms that have been specifically designed to improve flock performance, lessen disease severity, and reduce viral transmission. With the exception of certain autogenous vaccines, no vaccines currently exist to aid in the ...

Highlights of the 8th International Conference on Vaccines for Enteric Diseases: the Scottish Encounter To Defeat Diarrheal Diseases

PubMed Central

Tennant, Sharon M.; Steele, A. Duncan

2016-01-01

Infectious diarrhea is a leading cause of morbidity and of mortality; the burden of disease affects individuals of all ages but particularly young children, especially those living in poor regions where the disease is endemic. It is also a health concern for international travelers to these areas. Experts on vaccines and enteric infections and advocates for global health improvement gathered in Scotland from 8 to 10 July 2015 to discuss recent advances in the assessment and understanding of the burden of enteric diseases and progress in the development and implementation of strategies to prevent these infections. Highlights of the meeting included description of advances in molecular assays to estimate pathogen-specific prevalence, methods to model epidemiologic trends, novel approaches to generate broad-spectrum vaccines, new initiatives to evaluate vaccine performance where they are most needed, renewed interest in human challenge models, immunological readouts as predictors of vaccine efficacy, maternal immunization to prevent enteric infections, and the impact of maternal immunity on the vaccine take of infants. A follow-up scientific gathering to advance Shigella and enterotoxigenic Escherichia coli (ETEC) vaccine efforts will be held from 28 to 30 June 2016 in Washington, DC. PMID:26936100

Oral vaccination of channel catfish against enteric septicemia of catfish using a live attenuated Edwardsiella ictaluri isolate

USDA-ARS?s Scientific Manuscript database

Enteric septicemia of catfish (ESC), caused by Edwardsiella ictaluri, is the most problematic bacterial disease affecting catfish aquaculture in the southeastern United States. Efforts to develop an effective ESC vaccine have had limited industrial success. In commercial settings, ESC vaccines are...

Enhanced vaccination effect against influenza by prebiotics in elderly patients receiving enteral nutrition.

PubMed

Akatsu, Hiroyasu; Nagafuchi, Shinya; Kurihara, Rina; Okuda, Kenji; Kanesaka, Takeshi; Ogawa, Norihiro; Kanematsu, Takayoshi; Takasugi, Satoshi; Yamaji, Taketo; Takami, Masao; Yamamoto, Takayuki; Ohara, Hirotaka; Maruyama, Mitsuo

2016-02-01

We investigated the effect of prebiotics on the immunological response after influenza vaccination in enterally fed elderly individuals. The intervention group was given an enteral formula containing lactic acid bacteria-fermented milk products. In addition, two different types of other prebiotics, galacto-oligosaccharide and bifidogenic growth stimulator, were also given. The two prebiotics improved intestinal microbiota differently. In a control group, a standard formula without prebiotics was given. An enteral formula with (intervention group [F]) or without (control group [C]) prebiotics was given through percutaneous endoscopic gastrostomy to elderly participants for 10 weeks. Influenza vaccine was inoculated at week 4. Nutritional and biochemical indices, intestinal micro bacteria and immunological indices were analyzed. The Bifidobacterium count in groups F and C at week 0 was 6.4 ± 1.9 and 6.6 ± 3.0 (log10 [count/g feces]), respectively. Although the count in group C decreased at week 10, the count in group F increased. The Bacteroides count in group F increased from 10.7 ± 0.9 to 11.4 ± 0.5, but decreased in group C from 11.2 ± 0.2 to 10.7 ± 0.4. Although the enhanced titers of H1N1, H3N2 and B antigens against the vaccine decreased thereafter in group C, these enhanced titers in group F could be maintained. Our findings suggest that prebiotics affect the intestinal microbiota and might maintain the antibody titers in elderly individuals. © 2015 Japan Geriatrics Society.

Oral vaccination of channel catfish against enteric septicemia of catfish (ESC) using a live attenuated Edwardsiella ictaluri isolate

USDA-ARS?s Scientific Manuscript database

Enteric septicemia of catfish (ESC), caused by Edwardsiella ictaluri, is the most problematic bacterial disease affecting catfish aquaculture in the southeastern United States. Efforts to develop an effective ESC vaccine have had limited industrial success. In commercial settings, ESC vaccines are t...

Status of vaccine research and development of vaccines for tuberculosis.

PubMed

Evans, Thomas G; Schrager, Lew; Thole, Jelle

2016-06-03

TB is now the single pathogen that causes the greatest mortality in the world, at over 1.6 million deaths each year. The widely used the 90 year old BCG vaccine appears to have minimal impact on the worldwide incidence despite some efficacy in infants. Novel vaccine development has accelerated in the past 15 years, with 15 candidates entering human trials; two vaccines are now in large-scale efficacy studies. Modeling by three groups has consistently shown that mass vaccination that includes activity in the latently infected population, especially adolescents and young adults, will likely have the largest impact on new disease transmission. At present the field requires better validated animal models, better understanding of a correlate of immunity, new cost-effective approaches to Proof of Concept trials, and increased appreciation by the public health and scientific community for the size of the problem and the need for a vaccine. Such a vaccine is likely to also play a role in the era of increasing antibiotic resistance. Ongoing efforts and studies are working to implement these needs over the next 5 years, which will lead to an understanding that will increase the likelihood of a successful TB vaccine. Copyright © 2016 World Health Organization. Published by Elsevier Ltd.. All rights reserved.

A brief review on the immunological scenario and recent developmental status of vaccines against enteric fever.

PubMed

Howlader, Debaki Ranjan; Koley, Hemanta; Maiti, Suhrid; Bhaumik, Ushasi; Mukherjee, Priyadarshini; Dutta, Shanta

2017-11-07

Enteric fever has been one of the leading causes of severe illness and deaths worldwide. S. Typhi and S. Paratyphi A, B and C are important enteric fever-causing organisms globally. This infection causes about 21 million cases among which 222,000 typhoid related deaths occurred in 2015. These estimates do not reflect the ultimate and real status of the disease due to the lack of unified diagnostic and proper reporting system from typhoid endemic and other regions. Current control strategies have become increasingly ineffective due to the emergence of multi-drug resistance among the strains. This situation worsens the disease-burden in developing as well as in developed countries. Moreover the emergence of S. Paratyphi A as a major enteric fever-causing organism in several Asian countries, demands a prophylactic measure at this hour. Other than two licensed vaccines of S. Typhi, there are no exsisting vaccines for S. Paratyphi A. Moreover, travelers returning from endemic regions are becoming more susceptible to have these infections. In this situation, a need for bivalent approach is required where a single immunogen (consisting from each organism) will be effective against the disease. In this review, we have focused on the general information about typhoidal fever, its spread and epidemiology in brief and the present status of typhoidal vaccines and its future. This review highlights existing gaps in the typhoidal salmonellae research with a special emphasis on the status of present typhoidal salmonellae vaccine research. Copyright © 2017 Elsevier Ltd. All rights reserved.

Marker vaccine strategies and candidate CSFV marker vaccines.

PubMed

Dong, Xiao-Nan; Chen, Ying-Hua

2007-01-04

Classical swine fever (CSF) is an economically important highly contagious disease of swine worldwide. Classical swine fever virus (CSFV) is its etiological agent, and the only natural hosts are domestic pigs and wild boars. Although field CSFV strains vary in the virulence, they all result in serious losses in pig industry. Highly virulent field strains generally cause acute disease and high mortality; moderately virulent field strains raise subacute or chronic infections; postnatal infection by low virulent field strains produces subclinical infection and mortality in the new-born piglets. CSFV can cross the placental barrier, and this transplacental transmission usually results in mortality of fetuses and birth of congenitally infected pigs with a late-onset disease and death. Two main strategies to control CSF epidemic are systematic prophylactic vaccination with live attenuated vaccines (such as C-strain) and non-vaccination stamping-out policy. But neither of them is satisfying enough. Marker vaccine and companion serological diagnostic test is thought to be a promising strategy for future control and eradication of CSF. During the past 15 years, various candidate marker vaccines were constructed and evaluated in the animal experiments, including recombinant chimeric vaccines, recombinant deletion vaccines, DNA vaccines, subunit vaccines and peptide vaccines. Among them, two subunit vaccines entered the large scale marker vaccine trial of EU in 1999. Although they failed to fulfil all the demands of the Scientific Veterinary Committee, they successfully induced solid immunity against CSFV in the vaccinated pigs. It can be expected that new potent marker vaccines might be commercially available and used in systematic prophylactic vaccination campaign or emergency vaccination in the next 15 years. Here, we summarized current strategies and candidate CSFV marker vaccines. These strategies and methods are also helpful for the development of new

The Vaccination Confidence Scale: A Brief Measure of Parents’ Vaccination Beliefs

PubMed Central

Gilkey, Melissa B.; Magnus, Brooke E.; Reiter, Paul L.; McRee, Annie-Laurie; Dempsey, Amanda F.; Brewer, Noel T.

2015-01-01

Purpose The success of national immunization programs depends on the public’s confidence in vaccines. We sought to develop a scale for measuring confidence about adolescent vaccination in diverse populations of parents. Methods Data came from 9,623 parents who completed the 2010 National Immunization Survey-Teen, an annual, population-based telephone survey. Parents reported on a 13- to 17-year-old child in their households. We used exploratory and confirmatory factor analysis to identify latent constructs underlying parents’ responses to 8 vaccination belief survey items (response scale 0–10) conceptualized using the Health Belief Model. We assessed the scale’s psychometric properties overall and across demographic subgroups. Results Parents’ confidence about adolescent vaccination was generally high. Analyses provided support for three factors assessing benefits of vaccination (mean = 8.5), harms of vaccination (mean = 3.3), and trust in healthcare providers (mean = 9.0). The model showed good fit both overall (comparative fit index = 0.97) and across demographic subgroups, although internal consistency was variable for the three factors. We found lower confidence among several potentially vulnerable subpopulations, including mothers with lower levels of education and parents whose children were of Hispanic ethnicity (both p<.05). Conclusions Our brief, three-factor scale offers an efficient way to measure confidence in adolescent vaccination across demographic subgroups. Given evidence of lower confidence by educational attainment and race/ethnicity, program planners should consider factors such as health literacy and cultural competence when designing interventions to promote adolescent vaccination to ensure these programs are fully accessible. PMID:25258098

A large-scale field randomized trial demonstrates safety and efficacy of the vaccine LetiFend® against canine leishmaniosis.

PubMed

Fernández Cotrina, Javier; Iniesta, Virginia; Monroy, Isabel; Baz, Victoria; Hugnet, Christophe; Marañon, Francisco; Fabra, Mercedes; Gómez-Nieto, Luis Carlos; Alonso, Carlos

2018-04-05

Canine leishmaniosis is a zoonotic disease caused by Leishmania infantum. Extensive research is currently ongoing to develop safe and effective vaccines to protect from disease development. The European Commission has granted a marketing authorization for LetiFend®, a new vaccine containing recombinant Protein Q. The efficacy of LetiFend® vaccination in a large-scale dog population of both sexes, different breeds and ages in endemic areas is reported in this multicenter, randomized, double-blind, placebo-controlled field trial. Dogs (n = 549) living in France and Spain were randomly selected to receive a single subcutaneous dose of LetiFend® or placebo per year, and were naturally exposed to two L. infantum transmission seasons. Clinical examinations, blood and lymphoid organ sampling to evaluate serological, parasitological and disease status of the dogs were performed at different time points during the study. LetiFend® was very well tolerated and clearly reduced the incidence of clinical signs related to leishmaniosis. The number of confirmed cases of leishmaniosis was statistically significantly lower in the vaccine group. The number of dogs with parasites was close to be significantly reduced in the vaccine group (p = 0.0564). Re-vaccination of seropositive dogs demonstrated to be safe and not to worsen the course of the disease. The likelihood that a dog vaccinated with LetiFend® develops a confirmed case or clinical signs of leishmaniosis in areas with high pressure is, respectively, 5 and 9.8 time less than that for an unvaccinated dog. Thus, the overall efficacy of the LetiFend® vaccine in the prevention of confirmed cases of leishmaniosis in endemic areas with high disease pressure was shown to be 72%. In conclusion, this field trial demonstrates that LetiFend® is a novel, safe and effective vaccine for the active immunization of non-infected dogs from 6 months of age in reducing the risk of developing clinical leishmaniosis after natural

Understanding the Dimensions of Anti-Vaccination Attitudes: the Vaccination Attitudes Examination (VAX) Scale.

PubMed

Martin, Leslie R; Petrie, Keith J

2017-10-01

Anti-vaccination attitudes are important predictors of vaccination behavior. Existing measures of vaccination attitudes focus on specific age groups and/or particular vaccines; a more comprehensive measure would facilitate comparisons across studies. The aim of this study was to develop a short measure of general vaccination attitudes and establish its reliability and validity. Two studies were conducted using the VAX scale. For Study 1, participants were 409 individuals (53% female), with a mean age of 34.5 years. For Study 2, participants were 92 individuals (67% female) with a mean age of 28.6. Participants answered paper-and-pencil questions about their attitudes toward vaccines, prior and expected-future vaccination behaviors, perceived sensitivity to medicines, online behavior, and basic demographic information. Exploratory and confirmatory factor analyses were conducted with correlations and t tests then used to assess the scale's reliability and validity. Four distinct but correlated vaccine attitudes were identified: (1) mistrust of vaccine benefit, (2) worries about unforeseen future effects, (3) concerns about commercial profiteering, and (4) preference for natural immunity. These factors were significantly related to prior vaccination behavior, future intentions to obtain recommended vaccinations, perceived sensitivity to medicines, and the tendency to obtain health information online. The VAX scale provides an efficient method for identifying those with vaccination resistance, and the four subscales enable a more nuanced understanding of the nature of those views. It should be noted, however, that the strong correlations amongst the four subscales suggest that interventions should target all four attitude areas, and it remains to be seen whether differential emphasis across the four areas is warranted.

Real-time PCR-based infectivity assay for the titration of turkey hemorrhagic enteritis virus, an adenovirus, in live vaccines.

PubMed

Mahsoub, Hassan M; Evans, Nicholas P; Beach, Nathan M; Yuan, Lijuan; Zimmerman, Kurt; Pierson, Frank W

2017-01-01

The current in vitro titration method for turkey hemorrhagic enteritis virus (THEV) is the end-point dilution assay (EPD) in suspension cell culture (CC). This assay is subjective and results in high variability among vaccine lots. In this study, a new in vitro infectivity method combining a SYBR Green I-based qPCR assay and CC was developed for titration of live hemorrhagic enteritis (HE) CC vaccines. The qPCR was used to determine the virus genome copy number (vGCN) of the internalized virus particles following inoculation of susceptible RP19 cells with 1 vaccine label dose. The measured vGCN represents the number of infectious viral particles (IVP) per 1 dose. This method was used to compare 9 vaccine lots from 3 companies in the United States. Significant lot-to-lot variations within the same company and among the various companies were found in genomic and qPCR-based infectious titer per label dose. A positive linear relationship was found between qPCR infectious titer and genomic titer. Further, considerable variations in CCID 50 titers were found among tested vaccine lots, indicating the high variability of the current titration methods. The new method provides an alternative to classical titration assays and can help reduce variation among HE vaccine products. Copyright © 2016 Elsevier B.V. All rights reserved.

Field Trial of Attenuated Salmonella Typhi Live Oral Vaccine TY21A in Liquid and Enteric-Coated Formulations and Epidemiological Survey for Incidence of Diarrhea due to Shigella Species

DTIC Science & Technology

1989-03-01

and absolute efficacy of three doses of Ty2la vaccine given in enteric-coated capsule or liquid formulation. Intensive clinical and bacteriologic...TABLES Table 1. Evaluation of the efficacy of three doses of the enteric-coated capsule formulation of Ty2la live oral vaccine given within one week in...November, 1986 thzough February, 1989 of a field trial in Area Sur Oriente and Area Norte assessing the efficacy of Ty21a vaccine in liquid or enteric

Oral and Anal Vaccination Confers Full Protection against Enteric Redmouth Disease (ERM) in Rainbow Trout

PubMed Central

Ohtani, Maki; Strøm, Helene Kragelund; Raida, Martin Kristian

2014-01-01

The effect of oral vaccines against bacterial fish diseases has been a topic for debate for decades. Recently both M-like cells and dendritic cells have been discovered in the intestine of rainbow trout. It is therefore likely that antigens reaching the intestine can be taken up and thereby induce immunity in orally vaccinated fish. The objective of this project was to investigate whether oral and anal vaccination of rainbow trout induces protection against an experimental waterborne infection with the pathogenic enterobacteria Yersinia ruckeri O1 biotype 1 the causative agent of enteric redmouth disease (ERM). Rainbow trout were orally vaccinated with AquaVac ERM Oral (MERCK Animal Health) or an experimental vaccine bacterin of Y. ruckeri O1. Both vaccines were tested with and without a booster vaccination four months post the primary vaccination. Furthermore, two groups of positive controls were included, one group receiving the experimental oral vaccine in a 50 times higher dose, and the other group receiving a single dose administered anally in order to bypass the stomach. Each group was bath challenged with 6.3×108 CFU/ml Y. ruckeri, six months post the primary vaccination. The challenge induced significant mortality in all the infected groups except for the groups vaccinated anally with a single dose or orally with the high dose of bacterin. Both of these groups had 100% survival. These results show that a low dose of Y. ruckeri bacterin induces full protection when the bacterin is administered anally. Oral vaccination also induces full protection, however, at a dose 50 times higher than if the fish were to be vaccinated anally. This indicates that much of the orally fed antigen is digested in the stomach before it reaches the second segment of the intestine where it can be taken up as immunogenic antigens and presented to lymphocytes. PMID:24705460

Construction of recombinant Newcastle disease virus expressing the S1 protein of Turkey enteric coronavirus for use as a bivalent vaccine

USDA-ARS?s Scientific Manuscript database

Turkey enteric coronavirus (TCoV) causes a contagious form of enteritis in turkeys, generally recognized in the field by outward signs including diarrhea and decreased weight gain, resulting in severe economic losses for the poultry industry in the US. To date there is no commercial vaccine availab...

Shigella Isolates From the Global Enteric Multicenter Study Inform Vaccine Development

PubMed Central

Livio, Sofie; Strockbine, Nancy A.; Panchalingam, Sandra; Tennant, Sharon M.; Barry, Eileen M.; Marohn, Mark E.; Antonio, Martin; Hossain, Anowar; Mandomando, Inacio; Ochieng, John B.; Oundo, Joseph O.; Qureshi, Shahida; Ramamurthy, Thandavarayan; Tamboura, Boubou; Adegbola, Richard A.; Hossain, Mohammed Jahangir; Saha, Debasish; Sen, Sunil; Faruque, Abu Syed Golam; Alonso, Pedro L.; Breiman, Robert F.; Zaidi, Anita K. M.; Sur, Dipika; Sow, Samba O.; Berkeley, Lynette Y.; O'Reilly, Ciara E.; Mintz, Eric D.; Biswas, Kousick; Cohen, Dani; Farag, Tamer H.; Nasrin, Dilruba; Wu, Yukun; Blackwelder, William C.; Kotloff, Karen L.; Nataro, James P.; Levine, Myron M.

2014-01-01

Background. Shigella, a major diarrheal disease pathogen worldwide, is the target of vaccine development. The Global Enteric Multicenter Study (GEMS) investigated burden and etiology of moderate-to-severe diarrheal disease in children aged <60 months and matched controls without diarrhea during 3 years at 4 sites in Africa and 3 in Asia. Shigella was 1 of the 4 most common pathogens across sites and age strata. GEMS Shigella serotypes are reviewed to guide vaccine development. Methods. Subjects' stool specimens/rectal swabs were transported to site laboratories in transport media and plated onto xylose lysine desoxycholate and MacConkey agar. Suspect Shigella colonies were identified by biochemical tests and agglutination with antisera. Shigella isolates were shipped to the GEMS Reference Laboratory (Baltimore, MD) for confirmation and serotyping of S. flexneri; one-third of isolates were sent to the Centers for Disease Control and Prevention for quality control. Results. Shigella dysenteriae and S. boydii accounted for 5.0% and 5.4%, respectively, of 1130 Shigella case isolates; S. flexneri comprised 65.9% and S. sonnei 23.7%. Five serotypes/subserotypes comprised 89.4% of S. flexneri, including S. flexneri 2a, S. flexneri 6, S. flexneri 3a, S. flexneri 2b, and S. flexneri 1b. Conclusions. A broad-spectrum Shigella vaccine must protect against S. sonnei and 15 S. flexneri serotypes/subserotypes. A quadrivalent vaccine with O antigens from S. sonnei, S. flexneri 2a, S. flexneri 3a, and S. flexneri 6 can provide broad direct coverage against these most common serotypes and indirect coverage against all but 1 (rare) remaining subserotype through shared S. flexneri group antigens. PMID:24958238

Field Trials of Attenuated Salmonella Typhi Live Oral Vaccine TY21A in Liquid and Enteric-Coated Capsule Formulations in Santiago, Chile

DTIC Science & Technology

1990-06-01

inactive piacebo, children in the control group received viable Lactobacillus acidophilus because some experimental data suggest that L. acidophilus may...was the enteric-coating used to make the capsules acid-resistant. Such capsules, each containing 1-3 x 109 viable vaccine (or Lactobacillus ) organisms...formulation of vaccine (or of the Lactobacillus control preparation) consisted of two aluminum foil packets, one containing lyophilized vaccine (or

Shigella isolates from the global enteric multicenter study inform vaccine development.

PubMed

Livio, Sofie; Strockbine, Nancy A; Panchalingam, Sandra; Tennant, Sharon M; Barry, Eileen M; Marohn, Mark E; Antonio, Martin; Hossain, Anowar; Mandomando, Inacio; Ochieng, John B; Oundo, Joseph O; Qureshi, Shahida; Ramamurthy, Thandavarayan; Tamboura, Boubou; Adegbola, Richard A; Hossain, Mohammed Jahangir; Saha, Debasish; Sen, Sunil; Faruque, Abu Syed Golam; Alonso, Pedro L; Breiman, Robert F; Zaidi, Anita K M; Sur, Dipika; Sow, Samba O; Berkeley, Lynette Y; O'Reilly, Ciara E; Mintz, Eric D; Biswas, Kousick; Cohen, Dani; Farag, Tamer H; Nasrin, Dilruba; Wu, Yukun; Blackwelder, William C; Kotloff, Karen L; Nataro, James P; Levine, Myron M

2014-10-01

Shigella, a major diarrheal disease pathogen worldwide, is the target of vaccine development. The Global Enteric Multicenter Study (GEMS) investigated burden and etiology of moderate-to-severe diarrheal disease in children aged <60 months and matched controls without diarrhea during 3 years at 4 sites in Africa and 3 in Asia. Shigella was 1 of the 4 most common pathogens across sites and age strata. GEMS Shigella serotypes are reviewed to guide vaccine development. Subjects' stool specimens/rectal swabs were transported to site laboratories in transport media and plated onto xylose lysine desoxycholate and MacConkey agar. Suspect Shigella colonies were identified by biochemical tests and agglutination with antisera. Shigella isolates were shipped to the GEMS Reference Laboratory (Baltimore, MD) for confirmation and serotyping of S. flexneri; one-third of isolates were sent to the Centers for Disease Control and Prevention for quality control. Shigella dysenteriae and S. boydii accounted for 5.0% and 5.4%, respectively, of 1130 Shigella case isolates; S. flexneri comprised 65.9% and S. sonnei 23.7%. Five serotypes/subserotypes comprised 89.4% of S. flexneri, including S. flexneri 2a, S. flexneri 6, S. flexneri 3a, S. flexneri 2b, and S. flexneri 1b. A broad-spectrum Shigella vaccine must protect against S. sonnei and 15 S. flexneri serotypes/subserotypes. A quadrivalent vaccine with O antigens from S. sonnei, S. flexneri 2a, S. flexneri 3a, and S. flexneri 6 can provide broad direct coverage against these most common serotypes and indirect coverage against all but 1 (rare) remaining subserotype through shared S. flexneri group antigens. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

Latency of Varicella Zoster Virus in Dorsal Root, Cranial, and Enteric Ganglia in Vaccinated Children

PubMed Central

Gershon, Anne A.; Chen, Jason; Davis, Larry; Krinsky, Clarissa; Cowles, Robert; Reichard, Ross; Gershon, Michael

2012-01-01

Despite vaccination, varicella-zoster virus (VZV) remains an important pathogen. We investigated VZV latency in autopsy specimens from vaccinees, in gastrointestinal tissue removed surgically, and in a guinea pig model. We propose that retrograde transport from infected skin and viremia deliver VZV to neurons in which it becomes latent. Wild type (WT) VZV was found to be latent in many ganglia of vaccinated children with no history of varicella, suggesting that subclinical infection with WT-VZV occurs with subsequent viremic dissemination. The 30% to 40% rate of WT-VZV zoster reported in vaccinees and occasional trigeminal zoster due to vaccine type VZV (vOka) are consistent with viremic delivery of VZV to multiple ganglia. Most human intestinal specimens contained latent VZV within neurons of the enteric nervous system (ENS). Induction of viremia in guinea pigs led to VZV latency throughout the ENS. The possibility VZV reactivation in the ENS is an unsuspected cause of gastrointestinal disease requires future investigation. PMID:23303966

Duck Enteritis Virus Glycoprotein D and B DNA Vaccines Induce Immune Responses and Immunoprotection in Pekin Ducks

PubMed Central

Zhao, Yan; Cao, Yongsheng; Cui, Lihong; Ma, Bo; Mu, Xiaoyu; Li, Yanwei; Zhang, Zhihui; Li, Dan; Wei, Wei; Gao, Mingchun; Wang, Junwei

2014-01-01

DNA vaccine is a promising strategy for protection against virus infection. However, little is known on the efficacy of vaccination with two plasmids for expressing the glycoprotein D (gD) and glycoprotein B (gB) of duck enteritis virus (DEV) in inducing immune response and immunoprotection against virulent virus infection in Pekin ducks. In this study, two eukaryotic expressing plasmids of pcDNA3.1-gB and pcDNA3.1-gD were constructed. Following transfection, the gB and gD expressions in DF1 cells were detected. Groups of ducks were vaccinated with pcDNA3.1-gB and/or pcDNA3.1-gD, and boosted with the same vaccine on day 14 post primary vaccination. We found that intramuscular vaccinations with pcDNA3.1-gB and/or pcDNA3.1-gD, but not control plasmid, stimulated a high frequency of CD4+ and CD8+ T cells in Pekin ducks, particularly with both plasmids. Similarly, vaccination with these plasmids, particularly with both plasmids, promoted higher levels of neutralization antibodies against DEV in Pekin ducks. More importantly, vaccination with both plasmids significantly reduced the virulent DEV-induced mortality in Pekin ducks. Our data indicated that vaccination with plasmids for expressing both gB and gD induced potent cellular and humoral immunity against DEV in Pekin ducks. Therefore, this vaccination strategy may be used for the prevention of DEV infection in Pekin ducks. PMID:24736466

Duck enteritis virus glycoprotein D and B DNA vaccines induce immune responses and immunoprotection in Pekin ducks.

PubMed

Zhao, Yan; Cao, Yongsheng; Cui, Lihong; Ma, Bo; Mu, Xiaoyu; Li, Yanwei; Zhang, Zhihui; Li, Dan; Wei, Wei; Gao, Mingchun; Wang, Junwei

2014-01-01

DNA vaccine is a promising strategy for protection against virus infection. However, little is known on the efficacy of vaccination with two plasmids for expressing the glycoprotein D (gD) and glycoprotein B (gB) of duck enteritis virus (DEV) in inducing immune response and immunoprotection against virulent virus infection in Pekin ducks. In this study, two eukaryotic expressing plasmids of pcDNA3.1-gB and pcDNA3.1-gD were constructed. Following transfection, the gB and gD expressions in DF1 cells were detected. Groups of ducks were vaccinated with pcDNA3.1-gB and/or pcDNA3.1-gD, and boosted with the same vaccine on day 14 post primary vaccination. We found that intramuscular vaccinations with pcDNA3.1-gB and/or pcDNA3.1-gD, but not control plasmid, stimulated a high frequency of CD4+ and CD8+ T cells in Pekin ducks, particularly with both plasmids. Similarly, vaccination with these plasmids, particularly with both plasmids, promoted higher levels of neutralization antibodies against DEV in Pekin ducks. More importantly, vaccination with both plasmids significantly reduced the virulent DEV-induced mortality in Pekin ducks. Our data indicated that vaccination with plasmids for expressing both gB and gD induced potent cellular and humoral immunity against DEV in Pekin ducks. Therefore, this vaccination strategy may be used for the prevention of DEV infection in Pekin ducks.

Impact of enterovirus and other enteric pathogens on oral polio and rotavirus vaccine performance in Bangladeshi infants.

PubMed

Taniuchi, Mami; Platts-Mills, James A; Begum, Sharmin; Uddin, Md Jashim; Sobuz, Shihab U; Liu, Jie; Kirkpatrick, Beth D; Colgate, E Ross; Carmolli, Marya P; Dickson, Dorothy M; Nayak, Uma; Haque, Rashidul; Petri, William A; Houpt, Eric R

2016-06-08

Oral polio vaccine (OPV) and rotavirus vaccine (RV) exhibit poorer performance in low-income settings compared to high-income settings. Prior studies have suggested an inhibitory effect of concurrent non-polio enterovirus (NPEV) infection, but the impact of other enteric infections has not been comprehensively evaluated. In urban Bangladesh, we tested stools for a broad range of enteric viruses, bacteria, parasites, and fungi by quantitative PCR from infants at weeks 6 and 10 of life, coincident with the first OPV and RV administration respectively, and examined the association between enteropathogen quantity and subsequent OPV serum neutralizing titers, serum rotavirus IgA, and rotavirus diarrhea. Campylobacter and enterovirus (EV) quantity at the time of administration of the first dose of OPV was associated with lower OPV1-2 serum neutralizing titers, while enterovirus quantity was also associated with diminished rotavirus IgA (-0.08 change in log titer per tenfold increase in quantity; P=0.037), failure to seroconvert (OR 0.78, 95% CI: 0.64-0.96; P=0.022), and breakthrough rotavirus diarrhea (OR 1.34, 95% CI: 1.05-1.71; P=0.020) after adjusting for potential confounders. These associations were not observed for Sabin strain poliovirus quantity. In this broad survey of enteropathogens and oral vaccine performance we find a particular association between EV carriage, particularly NPEV, and OPV immunogenicity and RV protection. Strategies to reduce EV infections may improve oral vaccine responses. ClinicalTrials.gov Identifier: NCT01375647. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Motors of influenza vaccination uptake and vaccination advocacy in healthcare workers: Development and validation of two short scales.

PubMed

Vallée-Tourangeau, Gaëlle; Promberger, Marianne; Moon, Karis; Wheelock, Ana; Sirota, Miroslav; Norton, Christine; Sevdalis, Nick

2017-09-25

Healthcare workers (HCWs) are an important priority group for vaccination against influenza, yet, flu vaccine uptake remains low among them. Psychosocial studies of HCWs' decisions to get vaccinated have commonly drawn on subjective expected utility models to assess predictors of vaccination, assuming HCWs' choices result from a rational information-weighing process. By contrast, we recast those decisions asa commitment to vaccination and we aimed to understand why HCWs may want to (rather than believe they need to) get vaccinated against the flu. This article outlines the development and validation of a 9-item measure of cognitive empowerment towards flu vaccination (MoVac-flu scale) and an 11-item measure of cognitive empowerment towards vaccination advocacy. Both scales were administered to 784 frontline NHS HCWs with direct patient contact between June 2014 and July 2015. The scales exhibited excellent reliability and a clear unidimensional factor structure. An examination of the nomological network of the cognitive empowerment construct in relation to HCWs' vaccination against the flu revealed that this construct was distinct from traditional measures of risk perception and the strongest predictor of HCWs' decisions to vaccinate. Similarly, cognitive empowerment in relation to vaccination advocacy was a strong predictor of HCWs' engagement with vaccination advocacy. These findings suggest that the cognitive empowerment construct has important implications for advancing our understanding of HCWs' decisions to vaccinate as well as their advocacy behavior. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Assessment of 2 Salmonella enterica serovar Typhimurium-based vaccines against necrotic enteritis in reducing colonization of chickens by Salmonella serovars of different serogroups.

PubMed

Jiang, Yanfen; Kulkarni, Raveendra R; Parreira, Valeria R; Poppe, Cornelius; Roland, Kenneth L; Prescott, John F

2010-10-01

This study assessed the protective efficacy of oral vaccination with 2 experimental attenuated Salmonella Typhimurium-vectored vaccines for necrotic enteritis in protecting chickens against intestinal colonization by common serovars of Salmonella belonging to the 4 major serogroups affecting chickens. Birds were vaccinated orally with 1 × 10⁸ colony-forming units (CFU) of 1 of the vaccine strains χ9241 and χ9352, which express a plasmid-encoded partial recombinant hypothetical protein gene (tHP) of Clostridium perfringens, at days 1 and 7 of age, and then were challenged at 14 d of age with 10⁶ CFU of Salmonella serovars Anatum, Enteritidis, Heidelberg, Kentucky, or Typhimurium (representative serovars of serogroups B, C, D, and E). Birds were necropsied at 4 wk of age, and samples were collected to determine reduction in tissue and intestinal colonization. The chickens vaccinated with χ9241-tHP showed reduced colonization by Salmonella Enteritidis (serogroup D) and by Salmonella Heidelberg and Salmonella Typhimurium (serogroup B) compared with the control birds. No reduction in colonization was observed in the chickens vaccinated with χ9352-tHP. There was an association between the efficacy of these vaccine strains in protecting against necrotic enteritis, assessed on an earlier occasion, and their efficacy in protecting against Salmonella colonization. Thus, the choice of an attenuated Salmonella Typhimurium vaccine vector for delivery of heterologous antigens to chickens should be based partly on the vaccine's value in protecting against colonization by serovars within serogroups B and D. Such vectors would have the additional benefit of reducing colonization of important Salmonella serovars.

The failure of an inactivated mink enteritis virus vaccine in four preparations to provide protection to dogs against challenge with canine parvovirus-2.

PubMed

Carman, S; Povey, C

1982-01-01

Four experimental vaccine preparations comprising a strain of mink enteritis virus inactivated by either formalin or beta-propiolactone, and either adjuvanted or nonadjuvanted, failed to stimulate a consistent serum antibody response in 20 vaccinated dogs and failed to protect all but one of these dogs against oral challenge with canine parvovirus-2.

Assessment of 2 Salmonella enterica serovar Typhimurium-based vaccines against necrotic enteritis in reducing colonization of chickens by Salmonella serovars of different serogroups

PubMed Central

Jiang, Yanfen; Kulkarni, Raveendra R.; Parreira, Valeria R.; Poppe, Cornelius; Roland, Kenneth L.; Prescott, John F.

2010-01-01

This study assessed the protective efficacy of oral vaccination with 2 experimental attenuated Salmonella Typhimurium-vectored vaccines for necrotic enteritis in protecting chickens against intestinal colonization by common serovars of Salmonella belonging to the 4 major serogroups affecting chickens. Birds were vaccinated orally with 1 × 108 colony-forming units (CFU) of 1 of the vaccine strains χ9241 and χ9352, which express a plasmid-encoded partial recombinant hypothetical protein gene (tHP) of Clostridium perfringens, at days 1 and 7 of age, and then were challenged at 14 d of age with 106 CFU of Salmonella serovars Anatum, Enteritidis, Heidelberg, Kentucky, or Typhimurium (representative serovars of serogroups B, C, D, and E). Birds were necropsied at 4 wk of age, and samples were collected to determine reduction in tissue and intestinal colonization. The chickens vaccinated with χ9241-tHP showed reduced colonization by Salmonella Enteritidis (serogroup D) and by Salmonella Heidelberg and Salmonella Typhimurium (serogroup B) compared with the control birds. No reduction in colonization was observed in the chickens vaccinated with χ9352-tHP. There was an association between the efficacy of these vaccine strains in protecting against necrotic enteritis, assessed on an earlier occasion, and their efficacy in protecting against Salmonella colonization. Thus, the choice of an attenuated Salmonella Typhimurium vaccine vector for delivery of heterologous antigens to chickens should be based partly on the vaccine’s value in protecting against colonization by serovars within serogroups B and D. Such vectors would have the additional benefit of reducing colonization of important Salmonella serovars. PMID:21197226

Conformational and Thermal Stability Improvements for the Large-Scale Production of Yeast-Derived Rabbit Hemorrhagic Disease Virus-Like Particles as Multipurpose Vaccine

PubMed Central

Méndez, Lídice; González, Nemecio; Parra, Francisco; Martín-Alonso, José M.; Limonta, Miladys; Sánchez, Kosara; Cabrales, Ania; Estrada, Mario P.; Rodríguez-Mallón, Alina; Farnós, Omar

2013-01-01

Recombinant virus-like particles (VLP) antigenically similar to rabbit hemorrhagic disease virus (RHDV) were recently expressed at high levels inside Pichia pastoris cells. Based on the potential of RHDV VLP as platform for diverse vaccination purposes we undertook the design, development and scale-up of a production process. Conformational and stability issues were addressed to improve process control and optimization. Analyses on the structure, morphology and antigenicity of these multimers were carried out at different pH values during cell disruption and purification by size-exclusion chromatography. Process steps and environmental stresses in which aggregation or conformational instability can be detected were included. These analyses revealed higher stability and recoveries of properly assembled high-purity capsids at acidic and neutral pH in phosphate buffer. The use of stabilizers during long-term storage in solution showed that sucrose, sorbitol, trehalose and glycerol acted as useful aggregation-reducing agents. The VLP emulsified in an oil-based adjuvant were subjected to accelerated thermal stress treatments. None to slight variations were detected in the stability of formulations and in the structure of recovered capsids. A comprehensive analysis on scale-up strategies was accomplished and a nine steps large-scale production process was established. VLP produced after chromatographic separation protected rabbits against a lethal challenge. The minimum protective dose was identified. Stabilized particles were ultimately assayed as carriers of a foreign viral epitope from another pathogen affecting a larger animal species. For that purpose, a linear protective B-cell epitope from Classical Swine Fever Virus (CSFV) E2 envelope protein was chemically coupled to RHDV VLP. Conjugates were able to present the E2 peptide fragment for immune recognition and significantly enhanced the peptide-specific antibody response in vaccinated pigs. Overall these results

The influence of vaccine-critical websites on perceiving vaccination risks.

PubMed

Betsch, Cornelia; Renkewitz, Frank; Betsch, Tilmann; Ulshöfer, Corina

2010-04-01

This large-scale Internet-experiment tests whether vaccine-critical pages raise perceptions of the riskiness of vaccinations and alter vaccination intentions. We manipulated the information environment (vaccine-critical website, control, both) and the focus of search (on vaccination risks, omission risks, no focus). Our analyses reveal that accessing vaccine-critical websites for five to 10 minutes increases the perception of risk of vaccinating and decreases the perception of risk of omitting vaccinations as well as the intentions to vaccinate. In line with the 'risk-as-feelings' approach, the affect elicited by the vaccine-critical websites was positively related to changes in risk perception.

Live attenuated human rotavirus vaccine, Rotarix.

PubMed

Bernstein, David I

2006-10-01

Rotavirus infections are the leading cause of severe gastroenteritis in young children worldwide. Recently two new rotavirus vaccines have entered the world market. This review provides a summary of the rationale, development, and evaluation of one of these vaccines, Rotarix. Rotarix is a live oral rotavirus vaccine developed from a single protective human strain following multiple passages in tissue culture to attenuate the strain. The vaccine is administered as two oral doses at approximately 2 and 4 months of age. Large safety and efficacy trials have shown the vaccine is safe, not associated with intussusception, and effective against the most common circulating human serotypes. Efficacy against severe rotavirus gastroenteritis and hospitalization have ranged from 85 to 100 percent.

Latest COBE results, large-scale data, and predictions of inflation

NASA Technical Reports Server (NTRS)

Kashlinsky, A.

1992-01-01

One of the predictions of the inflationary scenario of cosmology is that the initial spectrum of primordial density fluctuations (PDFs) must have the Harrison-Zeldovich (HZ) form. Here, in order to test the inflationary scenario, predictions of the microwave background radiation (MBR) anisotropies measured by COBE are computed based on large-scale data for the universe and assuming Omega-1 and the HZ spectrum on large scales. It is found that the minimal scale where the spectrum can first enter the HZ regime is found, constraining the power spectrum of the mass distribution to within the bias factor b. This factor is determined and used to predict parameters of the MBR anisotropy field. For the spectrum of PDFs that reaches the HZ regime immediately after the scale accessible to the APM catalog, the numbers on MBR anisotropies are consistent with the COBE detections and thus the standard inflation can indeed be considered a viable theory for the origin of the large-scale structure in the universe.

Vaccination Confidence and Parental Refusal/Delay of Early Childhood Vaccines.

PubMed

Gilkey, Melissa B; McRee, Annie-Laurie; Magnus, Brooke E; Reiter, Paul L; Dempsey, Amanda F; Brewer, Noel T

2016-01-01

To support efforts to address parental hesitancy towards early childhood vaccination, we sought to validate the Vaccination Confidence Scale using data from a large, population-based sample of U.S. parents. We used weighted data from 9,354 parents who completed the 2011 National Immunization Survey. Parents reported on the immunization history of a 19- to 35-month-old child in their households. Healthcare providers then verified children's vaccination status for vaccines including measles, mumps, and rubella (MMR), varicella, and seasonal flu. We used separate multivariable logistic regression models to assess associations between parents' mean scores on the 8-item Vaccination Confidence Scale and vaccine refusal, vaccine delay, and vaccination status. A substantial minority of parents reported a history of vaccine refusal (15%) or delay (27%). Vaccination confidence was negatively associated with refusal of any vaccine (odds ratio [OR] = 0.58, 95% confidence interval [CI], 0.54-0.63) as well as refusal of MMR, varicella, and flu vaccines specifically. Negative associations between vaccination confidence and measures of vaccine delay were more moderate, including delay of any vaccine (OR = 0.81, 95% CI, 0.76-0.86). Vaccination confidence was positively associated with having received vaccines, including MMR (OR = 1.53, 95% CI, 1.40-1.68), varicella (OR = 1.54, 95% CI, 1.42-1.66), and flu vaccines (OR = 1.32, 95% CI, 1.23-1.42). Vaccination confidence was consistently associated with early childhood vaccination behavior across multiple vaccine types. Our findings support expanding the application of the Vaccination Confidence Scale to measure vaccination beliefs among parents of young children.

Live Attenuated Vaccine Based on Duck Enteritis Virus against Duck Hepatitis A Virus Types 1 and 3

PubMed Central

Zou, Zhong; Ma, Ji; Huang, Kun; Chen, Huanchun; Liu, Ziduo; Jin, Meilin

2016-01-01

As causative agents of duck viral hepatitis, duck hepatitis A virus type 1 (DHAV-1) and type 3 (DHAV-3) causes significant economic losses in the duck industry. However, a licensed commercial vaccine that simultaneously controls both pathogens is currently unavailable. Here, we generated duck enteritis virus recombinants (rC-KCE-2VP1) containing both VP1 from DHAV-1 (VP1/DHAV-1) and VP1 from DHAV-3 (VP1/DHAV-3) between UL27 and UL26. A self-cleaving 2A-element of FMDV was inserted between the two different types of VP1, allowing production of both proteins from a single open reading frame. Immunofluorescence and Western blot analysis results demonstrated that both VP1 proteins were robustly expressed in rC-KCE-2VP1-infected chicken embryo fibroblasts. Ducks that received a single dose of rC-KCE-2VP1 showed potent humoral and cellular immune responses and were completely protected against challenges of both pathogenic DHAV-1 and DHAV-3 strains. The protection was rapid, achieved as early as 3 days after vaccination. Moreover, viral replication was fully blocked in vaccinated ducks as early as 1 week post-vaccination. These results demonstrated, for the first time, that recombinant rC-KCE-2VP1 is potential fast-acting vaccine against DHAV-1 and DHAV-3. PMID:27777571

Comparative analysis of the Parent Attitudes about Childhood Vaccines (PACV) short scale and the five categories of vaccine acceptance identified by Gust et al.

PubMed

Oladejo, Omolade; Allen, Kristen; Amin, Avnika; Frew, Paula M; Bednarczyk, Robert A; Omer, Saad B

2016-09-22

There is a need to develop a standardized tool to aid in identifying, measuring and classifying the unique needs of vaccine-hesitant parents (VHPs). This will also assist in designing tailored interventions to address these needs. The Parental Attitude about Childhood Vaccines (PACV) short scale developed by Opel et al., and the Gust et al. vaccine acceptance categories have been acknowledged as potentially useful tools to measure parental vaccine hesitancy. The PACV short scale requires further validation. In our study, we evaluated how the Gust et al. vaccine acceptance categories correspond with the PACV short scale. As part of a larger study on vaccine attitudes, using the PACV short scale and Gust et al. vaccine acceptance categories, we assessed the correlation between the two measures using Spearman correlation coefficient, and the association between the two measures using the Cochran-Mantel-Haentszel test of association. We used logistic regression modelling to compare the association between a child's up-to-date immunization status and (a) PACV short scale and (b) Gust et al. vaccine acceptance categories. The PACV short scale and Gust et al. vaccine acceptance categories were positively correlated (r=0.6, df=198, p<0.05), and the Cochran-Mantel-Haentszel test of association yielded a statistically significant association (p<0.05). The two scales similarly predicted children's up-to-date immunization status for all recommended childhood vaccines. The ability of the PACV short scale to identify and classify parental vaccine hesitancy is similar to classification using Gust et al. vaccine acceptance categories, and both measure linear entities. The PACV short scale is recommended for screening parents at their first pediatric visit because it is easier to administer. A clearer understanding of how to classify parental vaccine hesitancy can be used to design tailored interventions based on these classifications, to address their specific needs. Copyright �

Enteric Fever in a Tertiary Paediatric Hospital: A Retrospective Six-Year Review.

PubMed

Ahmad Hatib, Nur Adila; Chong, Chia Yin; Thoon, Koh Cheng; Tee, Nancy Ws; Krishnamoorthy, Subramania S; Tan, Natalie Wh

2016-07-01

Enteric fever is a multisystemic infection which largely affects children. This study aimed to analyse the epidemiology, clinical presentation, treatment and outcome of paediatric enteric fever in Singapore. A retrospective review of children diagnosed with enteric fever in a tertiary paediatric hospital in Singapore was conducted from January 2006 to January 2012. Patients with positive blood cultures for Salmonella typhi or paratyphi were identified from the microbiology laboratory information system. Data was extracted from their case records. Of 50 enteric fever cases, 86% were due to Salmonella typhi, with 16.3% being multidrug resistant (MDR) strains. Sixty-two percent of S. typhi isolates were of decreased ciprofloxacin susceptibility (DCS). Five cases were both MDR and DCS. The remaining 14% were Salmonella paratyphi A. There were only 3 indigenous cases. Ninety-four percent had travelled to typhoid-endemic countries, 70.2% to the Indian subcontinent and the rest to Indonesia and Malaysia. All patients infected with MDR strains had travelled to the Indian subcontinent. Anaemia was a significant finding in children with typhoid, as compared to paratyphoid fever (P = 0.04). Although all children were previously well, 14% suffered severe complications including shock, pericardial effusion and enterocolitis. None had typhoid vaccination prior to their travel to developing countries. Enteric fever is largely an imported disease in Singapore and has contributed to significant morbidity in children. The use of typhoid vaccine, as well as education on food and water hygiene to children travelling to developing countries, needs to be emphasised.

Cost-effectiveness comparison of response strategies to a large-scale anthrax attack on the chicago metropolitan area: impact of timing and surge capacity.

PubMed

Kyriacou, Demetrios N; Dobrez, Debra; Parada, Jorge P; Steinberg, Justin M; Kahn, Adam; Bennett, Charles L; Schmitt, Brian P

2012-09-01

Rapid public health response to a large-scale anthrax attack would reduce overall morbidity and mortality. However, there is uncertainty about the optimal cost-effective response strategy based on timing of intervention, public health resources, and critical care facilities. We conducted a decision analytic study to compare response strategies to a theoretical large-scale anthrax attack on the Chicago metropolitan area beginning either Day 2 or Day 5 after the attack. These strategies correspond to the policy options set forth by the Anthrax Modeling Working Group for population-wide responses to a large-scale anthrax attack: (1) postattack antibiotic prophylaxis, (2) postattack antibiotic prophylaxis and vaccination, (3) preattack vaccination with postattack antibiotic prophylaxis, and (4) preattack vaccination with postattack antibiotic prophylaxis and vaccination. Outcomes were measured in costs, lives saved, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). We estimated that postattack antibiotic prophylaxis of all 1,390,000 anthrax-exposed people beginning on Day 2 after attack would result in 205,835 infected victims, 35,049 fulminant victims, and 28,612 deaths. Only 6,437 (18.5%) of the fulminant victims could be saved with the existing critical care facilities in the Chicago metropolitan area. Mortality would increase to 69,136 if the response strategy began on Day 5. Including postattack vaccination with antibiotic prophylaxis of all exposed people reduces mortality and is cost-effective for both Day 2 (ICER=$182/QALY) and Day 5 (ICER=$1,088/QALY) response strategies. Increasing ICU bed availability significantly reduces mortality for all response strategies. We conclude that postattack antibiotic prophylaxis and vaccination of all exposed people is the optimal cost-effective response strategy for a large-scale anthrax attack. Our findings support the US government's plan to provide antibiotic prophylaxis and

Cost-Effectiveness Comparison of Response Strategies to a Large-Scale Anthrax Attack on the Chicago Metropolitan Area: Impact of Timing and Surge Capacity

PubMed Central

Dobrez, Debra; Parada, Jorge P.; Steinberg, Justin M.; Kahn, Adam; Bennett, Charles L.; Schmitt, Brian P.

2012-01-01

Rapid public health response to a large-scale anthrax attack would reduce overall morbidity and mortality. However, there is uncertainty about the optimal cost-effective response strategy based on timing of intervention, public health resources, and critical care facilities. We conducted a decision analytic study to compare response strategies to a theoretical large-scale anthrax attack on the Chicago metropolitan area beginning either Day 2 or Day 5 after the attack. These strategies correspond to the policy options set forth by the Anthrax Modeling Working Group for population-wide responses to a large-scale anthrax attack: (1) postattack antibiotic prophylaxis, (2) postattack antibiotic prophylaxis and vaccination, (3) preattack vaccination with postattack antibiotic prophylaxis, and (4) preattack vaccination with postattack antibiotic prophylaxis and vaccination. Outcomes were measured in costs, lives saved, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). We estimated that postattack antibiotic prophylaxis of all 1,390,000 anthrax-exposed people beginning on Day 2 after attack would result in 205,835 infected victims, 35,049 fulminant victims, and 28,612 deaths. Only 6,437 (18.5%) of the fulminant victims could be saved with the existing critical care facilities in the Chicago metropolitan area. Mortality would increase to 69,136 if the response strategy began on Day 5. Including postattack vaccination with antibiotic prophylaxis of all exposed people reduces mortality and is cost-effective for both Day 2 (ICER=$182/QALY) and Day 5 (ICER=$1,088/QALY) response strategies. Increasing ICU bed availability significantly reduces mortality for all response strategies. We conclude that postattack antibiotic prophylaxis and vaccination of all exposed people is the optimal cost-effective response strategy for a large-scale anthrax attack. Our findings support the US government's plan to provide antibiotic prophylaxis and

Vaccination Confidence and Parental Refusal/Delay of Early Childhood Vaccines

PubMed Central

Gilkey, Melissa B.; McRee, Annie-Laurie; Magnus, Brooke E.; Reiter, Paul L.; Dempsey, Amanda F.; Brewer, Noel T.

2016-01-01

Objective To support efforts to address parental hesitancy towards early childhood vaccination, we sought to validate the Vaccination Confidence Scale using data from a large, population-based sample of U.S. parents. Methods We used weighted data from 9,354 parents who completed the 2011 National Immunization Survey. Parents reported on the immunization history of a 19- to 35-month-old child in their households. Healthcare providers then verified children’s vaccination status for vaccines including measles, mumps, and rubella (MMR), varicella, and seasonal flu. We used separate multivariable logistic regression models to assess associations between parents’ mean scores on the 8-item Vaccination Confidence Scale and vaccine refusal, vaccine delay, and vaccination status. Results A substantial minority of parents reported a history of vaccine refusal (15%) or delay (27%). Vaccination confidence was negatively associated with refusal of any vaccine (odds ratio [OR] = 0.58, 95% confidence interval [CI], 0.54–0.63) as well as refusal of MMR, varicella, and flu vaccines specifically. Negative associations between vaccination confidence and measures of vaccine delay were more moderate, including delay of any vaccine (OR = 0.81, 95% CI, 0.76–0.86). Vaccination confidence was positively associated with having received vaccines, including MMR (OR = 1.53, 95% CI, 1.40–1.68), varicella (OR = 1.54, 95% CI, 1.42–1.66), and flu vaccines (OR = 1.32, 95% CI, 1.23–1.42). Conclusions Vaccination confidence was consistently associated with early childhood vaccination behavior across multiple vaccine types. Our findings support expanding the application of the Vaccination Confidence Scale to measure vaccination beliefs among parents of young children. PMID:27391098

A novel multiplex poliovirus binding inhibition assay applicable for large serosurveillance and vaccine studies, without the use of live poliovirus.

PubMed

Schepp, Rutger M; Berbers, Guy A M; Ferreira, José A; Reimerink, Johan H; van der Klis, Fiona R

2017-03-01

Large-scale serosurveillance or vaccine studies for poliovirus using the "gold standard" WHO neutralisation test (NT) are very laborious and time consuming. With the polio eradication at hand and with the removal of live attenuated Sabin strains from the oral poliovirus vaccine (OPV), starting with type 2 (as of April 2016), laboratories will need to conform to much more stringent laboratory biosafety regulations when handling live poliovirus strains. In this study, a poliovirus binding inhibition multiplex immunoassay (polio MIA) using inactivated poliovirus vaccine (IPV-Salk) was developed for simultaneous quantification of serum antibodies directed to all three poliovirus types. Our assay shows a good correlation with the NT and an excellent correlation with the ELISA-based binding inhibition assay (POBI). The assay is highly type-specific and reproducible. Additionally, serum sample throughput increases about fivefold relative to NT and POBI and the amount of serum needed is reduced by more than 90%. In conclusion, the polio MIA can be used as a safe and high throughput application, especially for large-scale surveillance and vaccine studies, reducing laboratory time and serum amounts needed. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

East London Experience with Enteric Fever 2007-2012

PubMed Central

Dave, Jayshree; Millar, Michael; Maxeiner, Horst; Freedman, Joanne; Meade, Rachel; Rosmarin, Caryn; Jordan, Matthew; Andrews, Nick; Holliman, Richard; Sefton, Armine

2015-01-01

Purpose The clinical presentation and epidemiology for patients with enteric fever at two hospitals in East London during 2007–2012 is described with the aim to identify preventive opportunities and to reduce the cost of treatment. Methods A retrospective analysis of case notes from patients admitted with enteric fever during 2007 to 2012 with a microbiologically confirmed diagnosis was undertaken. Details on clinical presentation, travel history, demographic data, laboratory parameters, treatment, patient outcome and vaccination status were collected. Results Clinical case notes were available for 98/129 (76%) patients including 69 Salmonella enterica serovar Typhi (S. Typhi) and 29 Salmonella enterica serovar Paratyphi (S. Paratyphi). Thirty-four patients (35%) were discharged from emergency medicine without a diagnosis of enteric fever and then readmitted after positive blood cultures. Seventy-one of the 98 patients (72%) were UK residents who had travelled abroad, 23 (23%) were foreign visitors/new entrants to the UK and four (4%) had not travelled abroad. Enteric fever was not considered in the initial differential diagnosis for 48/98 (49%) cases. The median length of hospital stay was 7 days (range 0–57 days). The total cost of bed days for managing enteric fever was £454,000 in the two hospitals (mean £75,666/year). Median time to clinical resolution was five days (range 1–20). Seven of 98 (7%) patients were readmitted with relapsed or continued infection. Six of the 71 (8%) patients had received typhoid vaccination, 34 (48%) patients had not received vaccination, and for 31 cases (44%) vaccination status was unknown. Conclusions Further interventions regarding education and vaccination of travellers and recognition of the condition by emergency medicine clinicians in travellers to South Asia is required. PMID:25790017

Modelling the large-scale yellow fever outbreak in Luanda, Angola, and the impact of vaccination.

PubMed

Zhao, Shi; Stone, Lewi; Gao, Daozhou; He, Daihai

2018-01-01

Yellow fever (YF), transmitted via bites of infected mosquitoes, is a life-threatening viral disease endemic to tropical and subtropical regions of Africa and South America. YF has largely been controlled by widespread national vaccination campaigns. Nevertheless, between December 2015 and August 2016, YF resurged in Angola, quickly spread and became the largest YF outbreak for the last 30 years. Recently, YF resurged again in Brazil (December 2016). Thus, there is an urgent need to gain better understanding of the transmission pattern of YF. The present study provides a refined mathematical model, combined with modern likelihood-based statistical inference techniques, to assess and reconstruct important epidemiological processes underlying Angola's YF outbreak. This includes the outbreak's attack rate, the reproduction number ([Formula: see text]), the role of the mosquito vector, the influence of climatic factors, and the unusual but noticeable appearance of two-waves in the YF outbreak. The model explores actual and hypothetical vaccination strategies, and the impacts of possible human reactive behaviors (e.g., response to media precautions). While there were 73 deaths reported over the study period, the model indicates that the vaccination campaign saved 5.1-fold more people from death and saved from illness 5.6-fold of the observed 941 cases. Delaying the availability of the vaccines further would have greatly worsened the epidemic in terms of increased cases and deaths. The analysis estimated a mean [Formula: see text] and an attack rate of 0.09-0.15% (proportion of population infected) over the whole period from December 2015 to August 2016. Our estimated lower and upper bounds of [Formula: see text] are in line with previous studies. Unusually, [Formula: see text] oscillated in a manner that was "delayed" with the reported deaths. High recent number of deaths were associated (followed) with periods of relatively low disease transmission and low [Formula

Modelling the large-scale yellow fever outbreak in Luanda, Angola, and the impact of vaccination

PubMed Central

Zhao, Shi; Stone, Lewi; Gao, Daozhou

2018-01-01

Background Yellow fever (YF), transmitted via bites of infected mosquitoes, is a life-threatening viral disease endemic to tropical and subtropical regions of Africa and South America. YF has largely been controlled by widespread national vaccination campaigns. Nevertheless, between December 2015 and August 2016, YF resurged in Angola, quickly spread and became the largest YF outbreak for the last 30 years. Recently, YF resurged again in Brazil (December 2016). Thus, there is an urgent need to gain better understanding of the transmission pattern of YF. Model The present study provides a refined mathematical model, combined with modern likelihood-based statistical inference techniques, to assess and reconstruct important epidemiological processes underlying Angola’s YF outbreak. This includes the outbreak’s attack rate, the reproduction number (R0), the role of the mosquito vector, the influence of climatic factors, and the unusual but noticeable appearance of two-waves in the YF outbreak. The model explores actual and hypothetical vaccination strategies, and the impacts of possible human reactive behaviors (e.g., response to media precautions). Findings While there were 73 deaths reported over the study period, the model indicates that the vaccination campaign saved 5.1-fold more people from death and saved from illness 5.6-fold of the observed 941 cases. Delaying the availability of the vaccines further would have greatly worsened the epidemic in terms of increased cases and deaths. The analysis estimated a mean R0≈2.6-3.4 and an attack rate of 0.09-0.15% (proportion of population infected) over the whole period from December 2015 to August 2016. Our estimated lower and upper bounds of R0 are in line with previous studies. Unusually, R0 oscillated in a manner that was “delayed” with the reported deaths. High recent number of deaths were associated (followed) with periods of relatively low disease transmission and low R0, and vice-versa. The time

The impact of new technologies on vaccines.

PubMed

Talwar, G P; Diwan, M; Razvi, F; Malhotra, R

1999-01-01

Vast changes are taking place in vaccinology consequent to the introduction of new technologies. Amongst the vaccines included in the Expanded Programme of Immunization (EPI), the pertussis vaccine has been replaced by acellular purified fractions devoid of side-effects. Non-pathogenic but immunogenic mutants of tetanus and diptheria toxins are likely to replace the toxoids. An effective vaccine against hepatitis B prepared by recombinant technology is in large-scale use. Conjugated vaccines against Haemophilus influenzae b, S. pneumococcus and meningococcus are now available, as also vaccines against mumps, rubella and measles. Combination vaccines have been devised to limit the number of injections. Vaccine delivery systems have been developed to deliver multiple doses of the vaccine at a single contact point. A genetically-engineered oral vaccine for typhoid imparts better and longer duration of immunity. Oral vaccines for cholera and other enteric infections are under clinical trials. The nose as a route for immunization is showing promise for mucosal immunity and for anti-inflammatory experimental vaccines against multiple sclerosis and insulin-dependent diabetes mellitus. The range of vaccines has expanded to include pathogens resident in the body such as Helicobacter pylori (duodenal ulcer), S. mutans (dental caries), and human papilloma virus (carcinoma of the cervix). An important progress is the recognition that DNA alone can constitute the vaccines, inducing both humoral and cell-mediated immune responses. A large number of DNA vaccines have been made and shown interesting results in experimental animals. Live recombinant vaccines against rabies and rinderpest have proven to be highly effective for controlling these infections in the field, and those for AIDS are under clinical trial. Potent adjuvants have added to the efficacy of the vaccines. New technologies have emerged to 'humanize' mouse monoclonals by genetic engineering and express these

The Internal Consistency and Validity of the Vaccination Attitudes Examination Scale: A Replication Study.

PubMed

Wood, Louise; Smith, Michael; Miller, Christopher B; O'Carroll, Ronan E

2018-06-19

Vaccinations are important preventative health behaviors. The recently developed Vaccination Attitudes Examination (VAX) Scale aims to measure the reasons behind refusal/hesitancy regarding vaccinations. The aim of this replication study is to conduct an independent test of the newly developed VAX Scale in the UK. We tested (a) internal consistency (Cronbach's α); (b) convergent validity by assessing its relationships with beliefs about medication, medical mistrust, and perceived sensitivity to medicines; and (c) construct validity by testing how well the VAX Scale discriminated between vaccinators and nonvaccinators. A sample of 243 UK adults completed the VAX Scale, the Beliefs About Medicines Questionnaire, the Perceived Sensitivity to Medicines Scale, and the Medical Mistrust Index, in addition to demographics of age, gender, education levels, and social deprivation. Participants were asked (a) whether they received an influenza vaccination in the past year and (b) if they had a young child, whether they had vaccinated the young child against influenza in the past year. The VAX (a) demonstrated high internal consistency (α = .92); (b) was positively correlated with medical mistrust and beliefs about medicines, and less strongly correlated with perceived sensitivity to medicines; and (c) successfully differentiated parental influenza vaccinators from nonvaccinators. The VAX demonstrated good internal consistency, convergent validity, and construct validity in an independent UK sample. It appears to be a useful measure to help us understand the health beliefs that promote or deter vaccination behavior.

Human Vaccines & Immunotherapeutics

PubMed Central

Riedmann, Eva M.

2012-01-01

Two therapeutic HPV vaccine candidates successful in phase 1 Flu shot may prevent heart attacks and stroke CDX-1401 combined with TLR agonist: Positive phase 1 results Three MRSA vaccines in early clincial trials Ovarian cancer vaccine candidate DPX-Survivac: Positive interim results from phase 1 Chinese biotech partnership brings first hepatitis E vaccine to the market Therapeutic vaccine for treatment of genital herpes enters phase 2 Visionary concept: Printable vaccines PMID:23817319

The costs and effectiveness of large Phase III pre-licensure vaccine clinical trials.

PubMed

Black, Steven

2015-01-01

Prior to the 1980s, most vaccines were licensed based upon safety and effectiveness studies in several hundred individuals. Beginning with the evaluation of Haemophilus influenzae type b conjugate vaccines, much larger pre-licensure trials became common. The pre-licensure trial for Haemophilus influenzae oligosaccharide conjugate vaccine had more than 60,000 children and that of the seven-valent pneumococcal conjugate vaccine included almost 38,000 children. Although trial sizes for both of these studies were driven by the sample size required to demonstrate efficacy, the sample size requirements for safety evaluations of other vaccines have subsequently increased. With the demonstration of an increased risk of intussusception following the Rotashield brand rotavirus vaccine, this trend has continued. However, routinely requiring safety studies of 20,000-50,000 or more participants has two major downsides. First, the cost of performing large safety trials routinely prior to licensure of a vaccine is very large, with some estimates as high at US$200 million euros for one vaccine. This high financial cost engenders an opportunity cost whereby the number of vaccines that a company is willing or able to develop to meet public health needs becomes limited by this financial barrier. The second downside is that in the pre-licensure setting, such studies are very time consuming and delay the availability of a beneficial vaccine substantially. One might argue that in some situations, this financial commitment is warranted such as for evaluations of the risk of intussusception following newer rotavirus vaccines. However, it must be noted that while an increased risk of intussusception was not identified in large pre-licensure studies, in post marketing evaluations an increased risk of this outcome has been identified. Thus, even the extensive pre-licensure evaluations conducted did not identify an associated risk. The limitations of large Phase III trials have also been

Immunology of Gut Mucosal Vaccines

PubMed Central

Pasetti, Marcela F.; Simon, Jakub K.; Sztein, Marcelo B.; Levine, Myron M.

2011-01-01

Summary Understanding the mechanisms underlying the induction of immunity in the gastrointestinal mucosa following oral immunization and the cross-talk between mucosal and systemic immunity should expedite the development of vaccines to diminish the global burden caused by enteric pathogens. Identifying an immunological correlate of protection in the course of field trials of efficacy, animal models (when available), or human challenge studies is also invaluable. In industrialized country populations, live attenuated vaccines (e.g. polio, typhoid, and rotavirus) mimic natural infection and generate robust protective immune responses. In contrast, a major challenge is to understand and overcome the barriers responsible for the diminished immunogenicity and efficacy of the same enteric vaccines in underprivileged populations in developing countries. Success in developing vaccines against some enteric pathogens has heretofore been elusive (e.g. Shigella). Different types of oral vaccines can selectively or inclusively elicit mucosal secretory immunoglobulin A and serum immunoglobulin G antibodies and a variety of cell-mediated immune responses. Areas of research that require acceleration include interaction between the gut innate immune system and the stimulation of adaptive immunity, development of safe yet effective mucosal adjuvants, better understanding of homing to the mucosa of immunologically relevant cells, and elicitation of mucosal immunologic memory. This review dissects the immune responses elicited in humans by enteric vaccines. PMID:21198669

Vaccination with Clostridium perfringens recombinant proteins in combination with Montanide™ ISA 71 VG adjuvant increases protection against experimental necrotic enteritis in commercial broiler chickens

USDA-ARS?s Scientific Manuscript database

This study was performed to compare four Clostridium perfringens recombinant proteins as vaccine candidates using the Montanide™ ISA 71 VG adjuvant in an experimental model of necrotic enteritis. Broiler chickens were immunized with clostridial recombinant proteins with ISA 71 VG, and intestinal le...

Vaccination Policies: Requirements and Exemptions for Entering School.

PubMed

Skinner, Erik

2017-12-01

(1) According to the World Health Organization, immunization prevents between 2 million to 3 million deaths every year across the world. (2) When immunization rates are high, herd immunity develops and limits the spread of the disease, which helps protect those who cannot be vaccinated. (3) Vaccination rates for measles, mumps and rubella vary across the United States, ranging from 85.6 percent in Washington, D.C., to 99.4 percent in Mississippi.

Vaccines against invasive Salmonella disease

PubMed Central

MacLennan, Calman A; Martin, Laura B; Micoli, Francesca

2014-01-01

Though primarily enteric pathogens, Salmonellae are responsible for a considerable yet under-appreciated global burden of invasive disease. In South and South-East Asia, this manifests as enteric fever caused by serovars Typhi and Paratyphi A. In sub-Saharan Africa, a similar disease burden results from invasive nontyphoidal Salmonellae, principally serovars Typhimurium and Enteritidis. The existing Ty21a live-attenuated and Vi capsular polysaccharide vaccines target S. Typhi and are not effective in young children where the burden of invasive Salmonella disease is highest. After years of lack of investment in new Salmonella vaccines, recent times have seen increased interest in the area led by emerging-market manufacturers, global health vaccine institutes and academic partners. New glycoconjugate vaccines against S. Typhi are becoming available with similar vaccines against other invasive serovars in development. With other new vaccines under investigation, including live-attenuated, protein-based and GMMA vaccines, now is an exciting time for the Salmonella vaccine field. PMID:24804797

Plant-based vaccines against diarrheal diseases.

PubMed

Tacket, Carol O

2007-01-01

Every year 1.6 million deaths occur due to diarrhea related to unsafe water and inadequate sanitation-the vast majority in children under 5 years old. Safe and effective vaccines against enteric infections could contribute to control of these diseases. However, purification of protective antigens for inclusion in vaccines using traditional expression systems is expensive and unattractive to vaccine manufacturers who see the vaccine market as economically uninviting. Cost is one of the persistent barriers to deployment of new vaccines to populations that need them most urgently. Transgenic plant-derived vaccines offer a new strategy for development of safe, inexpensive vaccines against diarrheal diseases. In phase 1 clinical studies, these vaccines have been safe and immunogenic without the need for a buffer or vehicle other than the plant cell. This paper describes early clinical studies evaluating oral transgenic plant vaccines against enteric infections such as enterotoxigenic E. coli infection and norovirus.

Synergistic effect of embryo vaccination with Eimeria profilin and Clostridium perfringens NetB proteins on inducing protective immunity against necrotic enteritis in broiler chickens

USDA-ARS?s Scientific Manuscript database

The effects of embryo vaccination with Eimeria profilin plus Clostridium perfringens NetB toxin proteins in combination with the Montanide IMS-OVO adjuvant on the chicken immune response to necrotic enteritis were investigated using an E. maxima/C. perfringens co-infection model. Eighteen-day-old br...

European Vaccine Initiative: lessons from developing malaria vaccines.

PubMed

Geels, Mark J; Imoukhuede, Egeruan B; Imbault, Nathalie; van Schooten, Harry; McWade, Terry; Troye-Blomberg, Marita; Dobbelaer, Roland; Craig, Alister G; Leroy, Odile

2011-12-01

For over 10 years, the European Vaccine Initiative (EVI; European Malaria Vaccine Initiative until 2009) has contributed to the development of 24 malaria candidate vaccine antigens with 13 vaccine candidates being advanced into Phase I clinical trials, two of which have been transitioned for further clinical development in sub-Saharan Africa. Since its inception the EVI organization has operated as a funding agency, but with a clear service-oriented strategy. The scientific successes and difficulties encountered during these years and how these efforts have led to standardization and harmonization in vaccine development through large-scale European consortia are discussed. In the future, the EVI will remain instrumental in the pharmaceutical and clinical development of vaccines against 'diseases of poverty' with a continued focus on malaria. EVI will continue to focus on funding and managing preclinical evaluation up to Phase I/II clinical trials and strengthening the vaccine-development infrastructure in Europe, albeit with a global orientation.

The introduction of dengue vaccine may temporarily cause large spikes in prevalence.

PubMed

Pandey, A; Medlock, J

2015-04-01

A dengue vaccine is expected to be available within a few years. Once vaccine is available, policy-makers will need to develop suitable policies to allocate the vaccine. Mathematical models of dengue transmission predict complex temporal patterns in prevalence, driven by seasonal oscillations in mosquito abundance. In particular, vaccine introduction may induce a transient period immediately after vaccine introduction where prevalence can spike higher than in the pre-vaccination period. These spikes in prevalence could lead to doubts about the vaccination programme among the public and even among decision-makers, possibly impeding the vaccination programme. Using simple dengue transmission models, we found that large transient spikes in prevalence are robust phenomena that occur when vaccine coverage and vaccine efficacy are not either both very high or both very low. Despite the presence of transient spikes in prevalence, the models predict that vaccination does always reduce the total number of infections in the 15 years after vaccine introduction. We conclude that policy-makers should prepare for spikes in prevalence after vaccine introduction to mitigate the burden of these spikes and to accurately measure the effectiveness of the vaccine programme.

Validation of a scale to measure parental psychological empowerment in the vaccination decision.

PubMed

Marta, Fadda; Elisa, Galimberti; Luisa, Romanò; Marino, Faccini; Sabrina, Senatore; Alessandro, Zanetti; Peter J, Schulz

2017-09-21

Parents' empowerment is advocated to promote and preserve an informed and autonomous decision regarding their children' immunization. The scope of this study is to develop and evaluate the psychometric properties of an instrument to measure parents' psychological empowerment in their children's vaccination decision and propose a context-specific definition of this construct. Grounding in previous qualitative data, we generated an initial pool of items which was later content and face validated by a panel of experts. A pretest allowed us to reduce the initial pool to 9 items. Convergent and discriminant validity measures included the General Self-Efficacy Scale, a Psychological Empowerment Scale, and the Control Preference Scale. Vaccination-related outcomes such as attitude and intention were also included. Principal Component Analysis revealed a 2-factor structure, with each factor composed of 2 items. The first factor concerns the perceived influence of one's personal and family experience with vaccination, while the second factor represents the desire not to ask other parents about their experience with vaccination and their lack of interest in other parents' vaccination opinion. In light of its association with positive immunization-related outcomes, public health efforts should be directed to reinforce parents' empowerment.

Implementation research: reactive mass vaccination with single-dose oral cholera vaccine, Zambia.

PubMed

Poncin, Marc; Zulu, Gideon; Voute, Caroline; Ferreras, Eva; Muleya, Clara Mbwili; Malama, Kennedy; Pezzoli, Lorenzo; Mufunda, Jacob; Robert, Hugues; Uzzeni, Florent; Luquero, Francisco J; Chizema, Elizabeth; Ciglenecki, Iza

2018-02-01

To describe the implementation and feasibility of an innovative mass vaccination strategy - based on single-dose oral cholera vaccine - to curb a cholera epidemic in a large urban setting. In April 2016, in the early stages of a cholera outbreak in Lusaka, Zambia, the health ministry collaborated with Médecins Sans Frontières and the World Health Organization in organizing a mass vaccination campaign, based on single-dose oral cholera vaccine. Over a period of 17 days, partners mobilized 1700 health ministry staff and community volunteers for community sensitization, social mobilization and vaccination activities in 10 townships. On each day, doses of vaccine were delivered to vaccination sites and administrative coverage was estimated. Overall, vaccination teams administered 424 100 doses of vaccine to an estimated target population of 578 043, resulting in an estimated administrative coverage of 73.4%. After the campaign, few cholera cases were reported and there was no evidence of the disease spreading within the vaccinated areas. The total cost of the campaign - 2.31 United States dollars (US$) per dose - included the relatively low cost of local delivery - US$ 0.41 per dose. We found that an early and large-scale targeted reactive campaign using a single-dose oral vaccine, organized in response to a cholera epidemic within a large city, to be feasible and appeared effective. While cholera vaccines remain in short supply, the maximization of the number of vaccines in response to a cholera epidemic, by the use of just one dose per member of an at-risk community, should be considered.

Plant-Based Vaccines Against Diarrheal Diseases

PubMed Central

Tacket, Carol O.

2007-01-01

Every year 1.6 million deaths occur due to diarrhea related to unsafe water and inadequate sanitation—the vast majority in children under 5 years old. Safe and effective vaccines against enteric infections could contribute to control of these diseases. However, purification of protective antigens for inclusion in vaccines using traditional expression systems is expensive and unattractive to vaccine manufacturers who see the vaccine market as economically uninviting. Cost is one of the persistent barriers to deployment of new vaccines to populations that need them most urgently. Transgenic plant-derived vaccines offer a new strategy for development of safe, inexpensive vaccines against diarrheal diseases. In phase 1 clinical studies, these vaccines have been safe and immunogenic without the need for a buffer or vehicle other than the plant cell. This paper describes early clinical studies evaluating oral transgenic plant vaccines against enteric infections such as enterotoxigenic E. coli infection and norovirus. PMID:18528491

OCCURRENCE OF ENTERIC VIRUSES IN WATERS

EPA Science Inventory

A number of different types of human enteric viruses cause waterborne outbreaks when individuals are exposed to contaminated drinking and recreational waters. Vaccination against poliovirus has virtually eliminated poliomyelitis from the planet, but other members of the enterovi...

Marker vaccines and companion diagnostic tests for classical swine fever.

PubMed

Floegel-Niesmann, G

2003-01-01

For Classical Swine Fever (CSF) a subunit vaccine consisting of the E2 protein is commercially available. The discriminatory ELISAs detect antibodies against another viral protein, the E(rns). As CSF has already been eradicated from many countries the use of a marker vaccine in these regions can only be contemplated as emergency vaccination after a new introduction of virus. Therefore, a Large Scale Marker Vaccine Trial was financed by the EU Commission and organised by the EU Reference Laboratory for CSF in 1999. When tested under the conditions of emergency vaccination, e.g. challenge before full immunity had developed, it was shown, that most CSF challenge infections took a subclinical course with reduced virus shedding. Transplacental transmission in pregnant sows could not be prevented after an application of a single vaccine dose. The most serious deficiencies have been found in the discriminatory ELISAs. Both available tests have shown deficiencies in sensitivity and specificity compared to conventional CSF antibody ELISAs. At the time, when the trial was performed, no confirmatory test was available to verify the results of the discriminatory ELISAs. Currently two new developments of marker vaccines for CSF are in progress. A chimaeric vaccine is based on infectious clones of the conventional live vaccine (C-strain) where a gene is replaced with the corresponding gene of the closely related pestivirus Bovine Viral Diarrhoea (BVD) virus. Conversely, the E2 gene of a BVD virus can be replaced by the E2 of a virulent CSF virus. The other principle is the construction of a DNA vaccine, expressing the E2 gene after entering the host cell. Deletion mutants of the E2 gene have also been constructed and tested for their induction of immunity. Both new developments are based on the same discriminatory tests as mentioned previously and developments of other principles for discrimination are rare.

Technology transfer and scale-up of the Flublok recombinant hemagglutinin (HA) influenza vaccine manufacturing process.

PubMed

Buckland, Barry; Boulanger, Robert; Fino, Mireli; Srivastava, Indresh; Holtz, Kathy; Khramtsov, Nikolai; McPherson, Clifton; Meghrous, Jamal; Kubera, Paul; Cox, Manon M J

2014-09-22

Multiple different hemagglutinin (HA) protein antigens have been reproducibly manufactured at the 650L scale by Protein Sciences Corporation (PSC) based on an insect cell culture with baculovirus infection. Significantly, these HA protein antigens were produced by the same Universal Manufacturing process as described in the biological license application (BLA) for the first recombinant influenza vaccine approved by the FDA (Flublok). The technology is uniquely designed so that a change in vaccine composition can be readily accommodated from one HA protein antigen to another one. Here we present a vaccine candidate to combat the recently emerged H7N9 virus as an example starting with the genetic sequence for the required HA, creation of the baculovirus and ending with purified protein antigen (or vaccine component) at the 10L scale accomplished within 38 days under GMP conditions. The same process performance is being achieved at the 2L, 10L, 100L, 650L and 2500L scale. An illustration is given of how the technology was transferred from the benchmark 650L scale facility to a retrofitted microbial facility at the 2500L scale within 100 days which includes the time for facility engineering changes. The successful development, technology transfer and scale-up of the Flublok process has major implications for being ready to make vaccine rapidly on a worldwide scale as a defense against pandemic influenza. The technology described does not have the same vulnerability to mutations in the egg adapted strain, and resulting loss in vaccine efficacy, faced by egg based manufacture. Copyright © 2014 Elsevier Ltd. All rights reserved.

Implementation research: reactive mass vaccination with single-dose oral cholera vaccine, Zambia

PubMed Central

Zulu, Gideon; Voute, Caroline; Ferreras, Eva; Muleya, Clara Mbwili; Malama, Kennedy; Pezzoli, Lorenzo; Mufunda, Jacob; Robert, Hugues; Uzzeni, Florent; Luquero, Francisco J; Chizema, Elizabeth; Ciglenecki, Iza

2018-01-01

Abstract Objective To describe the implementation and feasibility of an innovative mass vaccination strategy – based on single-dose oral cholera vaccine – to curb a cholera epidemic in a large urban setting. Method In April 2016, in the early stages of a cholera outbreak in Lusaka, Zambia, the health ministry collaborated with Médecins Sans Frontières and the World Health Organization in organizing a mass vaccination campaign, based on single-dose oral cholera vaccine. Over a period of 17 days, partners mobilized 1700 health ministry staff and community volunteers for community sensitization, social mobilization and vaccination activities in 10 townships. On each day, doses of vaccine were delivered to vaccination sites and administrative coverage was estimated. Findings Overall, vaccination teams administered 424 100 doses of vaccine to an estimated target population of 578 043, resulting in an estimated administrative coverage of 73.4%. After the campaign, few cholera cases were reported and there was no evidence of the disease spreading within the vaccinated areas. The total cost of the campaign – 2.31 United States dollars (US$) per dose – included the relatively low cost of local delivery – US$ 0.41 per dose. Conclusion We found that an early and large-scale targeted reactive campaign using a single-dose oral vaccine, organized in response to a cholera epidemic within a large city, to be feasible and appeared effective. While cholera vaccines remain in short supply, the maximization of the number of vaccines in response to a cholera epidemic, by the use of just one dose per member of an at-risk community, should be considered. PMID:29403111

Tuberculosis vaccines in clinical trials

PubMed Central

Rowland, Rosalind; McShane, Helen

2011-01-01

Effective prophylactic and/or therapeutic vaccination is a key strategy for controlling the global TB epidemic. The partial effectiveness of the existing TB vaccine, bacille Calmette–Guérin (BCG), suggests effective vaccination is possible and highlights the need for an improved vaccination strategy. Clinical trials are evaluating both modifications to the existing BCG immunization methods and also novel TB vaccines, designed to replace or boost BCG. Candidate vaccines in clinical development include live mycobacterial vaccines designed to replace BCG, subunit vaccines designed to boost BCG and therapeutic vaccines designed as an adjunct to chemotherapy. There is a great need for validated animal models, identification of immunological biomarkers of protection and field sites with the capacity for large-scale efficacy testing in order to develop and license a novel TB vaccine or regimen. PMID:21604985

New insights into environmental enteric dysfunction

USDA-ARS?s Scientific Manuscript database

Environmental enteric dysfunction (EED) has been recognised as an important contributing factor to physical and cognitive stunting, poor response to oral vaccines, limited resilience to acute infections and ultimately global childhood mortality. The aetiology of EED remains poorly defined but the ep...

OCCURRENCE OF ENTERIC VIRUSES IN SURFACE WATERS

EPA Science Inventory

Human enteric viruses cause a number of diseases when individuals are exposed to contaminated drinking & recreational waters. Vaccination against poliovirus has virtually eliminated poliomyelitis from the planet. Other members of enterovirus group cause numerous diseases. Hepatit...

Generalized herd effects and vaccine evaluation: impact of live influenza vaccine on off-target bacterial colonisation.

PubMed

Mina, Michael J

2017-06-01

Interactions between pathogens and commensal microbes are major contributors to health and disease. Infectious diseases however are most often considered independent, viewed within a one-host one-pathogen paradigm and, by extension, the interventions used to treat and prevent them are measured and evaluated within this same paradigm. Vaccines, especially live vaccines, by stimulating immune responses or directly interacting with other microbes can alter the environment in which they act, with effects that span across pathogen species. Live attenuated infl uenza vaccines for example, while safe, increase upper respiratory tract bacterial carriage density of important human commensal pathogens like Streptococcus pneumoniae and Staphylococcus aureus. Further, by altering the ecological niche and dynamics of phylogenetically distinct microbes within the host, vaccines may unintentionally affect transmission of non-vaccine targeted pathogens. Thus, vaccine effects may span across species and across scales, from the individual to the population level. In keeping with traditional vaccine herd-effects that indirectly protect even unvaccinated individuals by reducing population prevalence of vaccine-targeted pathogens, we call these cross-species cross-scale effects "generalized herd-effects". As opposed to traditional herd-effects, "generalized" relaxes the assumption that the effect occurs at the level of the vaccine-target pathogen and "herd effect" implies, as usual, that the effects indirectly impact the population at large, including unvaccinated bystanders. Unlike traditional herd-effects that decrease population prevalence of the vaccine-target, generalized herd-effects may decrease or increase prevalence and disease by the off-target pathogen. LAIV, for example, by increasing pneumococcal density in the upper respiratory tract of vaccine recipients, especially children, may increase pneumococcal transmission and prevalence, leading to excess pneumococcal invasive

Vaccines

MedlinePlus Videos and Cool Tools

Vaccinations are injections of antigens into the body. Once the antigens enter the blood, they circulate along with other ... B and T cells. B and T cells are white blood cells that help the body defend ...

Results and harmonization guidelines from two large-scale international Elispot proficiency panels conducted by the Cancer Vaccine Consortium (CVC/SVI).

PubMed

Janetzki, Sylvia; Panageas, Katherine S; Ben-Porat, Leah; Boyer, Jean; Britten, Cedrik M; Clay, Timothy M; Kalos, Michael; Maecker, Holden T; Romero, Pedro; Yuan, Jianda; Kast, W Martin; Hoos, Axel

2008-03-01

The Cancer Vaccine Consortium of the Sabin Vaccine Institute (CVC/SVI) is conducting an ongoing large-scale immune monitoring harmonization program through its members and affiliated associations. This effort was brought to life as an external validation program by conducting an international Elispot proficiency panel with 36 laboratories in 2005, and was followed by a second panel with 29 participating laboratories in 2006 allowing for application of learnings from the first panel. Critical protocol choices, as well as standardization and validation practices among laboratories were assessed through detailed surveys. Although panel participants had to follow general guidelines in order to allow comparison of results, each laboratory was able to use its own protocols, materials and reagents. The second panel recorded an overall significantly improved performance, as measured by the ability to detect all predefined responses correctly. Protocol choices and laboratory practices, which can have a dramatic effect on the overall assay outcome, were identified and lead to the following recommendations: (A) Establish a laboratory SOP for Elispot testing procedures including (A1) a counting method for apoptotic cells for determining adequate cell dilution for plating, and (A2) overnight rest of cells prior to plating and incubation, (B) Use only pre-tested serum optimized for low background: high signal ratio, (C) Establish a laboratory SOP for plate reading including (C1) human auditing during the reading process and (C2) adequate adjustments for technical artifacts, and (D) Only allow trained personnel, which is certified per laboratory SOPs to conduct assays. Recommendations described under (A) were found to make a statistically significant difference in assay performance, while the remaining recommendations are based on practical experiences confirmed by the panel results, which could not be statistically tested. These results provide initial harmonization guidelines

Risk factors associated with parvovirus enteritis in dogs: 283 cases (1982-1991).

PubMed

Houston, D M; Ribble, C S; Head, L L

1996-02-15

To determine breed, sex, and seasonal predisposition for development of canine parvovirus (CPV) enteritis in dogs. Retrospective case-control study. Medical records from 283 dogs with confirmed CPV enteritis and from 834 age-matched control dogs that were healthy or had been admitted with nonenteric illness. Effects of season, breed, sex, and neutering on the risk of developing CPV enteritis were examined by calculation of unadjusted odds ratios and performance of multivariate analysis. Stratified and contingency table analyses were performed to identify interactions and confounding among variables. Rottweilers, American Pit Bull Terriers, Doberman Pinschers, and German Shepherd Dogs were at increased risk and Toy Poodles and Cocker Spaniels were at decreased risk for developing CPV enteritis, compared with that for mixed-breed dogs. For dogs more than 6 months old, sexually intact males were twice as likely as intact females to develop CPV enteritis. Dogs were 3 times more likely to be admitted with CPV enteritis in July, August, and September, compared with the rest of the year. Dogs were 12.7 times more likely to be admitted with CPV enteritis if they had not been currently vaccinated. Lack of vaccination is a significant risk factor for development of CPV enteritis. Seasonal, sex, and breed predispositions for the development of CPV enteritis also exist.

The Psychiatric Genomics Consortium Posttraumatic Stress Disorder Workgroup: Posttraumatic Stress Disorder Enters the Age of Large-Scale Genomic Collaboration

PubMed Central

Logue, Mark W; Amstadter, Ananda B; Baker, Dewleen G; Duncan, Laramie; Koenen, Karestan C; Liberzon, Israel; Miller, Mark W; Morey, Rajendra A; Nievergelt, Caroline M; Ressler, Kerry J; Smith, Alicia K; Smoller, Jordan W; Stein, Murray B; Sumner, Jennifer A; Uddin, Monica

2015-01-01

The development of posttraumatic stress disorder (PTSD) is influenced by genetic factors. Although there have been some replicated candidates, the identification of risk variants for PTSD has lagged behind genetic research of other psychiatric disorders such as schizophrenia, autism, and bipolar disorder. Psychiatric genetics has moved beyond examination of specific candidate genes in favor of the genome-wide association study (GWAS) strategy of very large numbers of samples, which allows for the discovery of previously unsuspected genes and molecular pathways. The successes of genetic studies of schizophrenia and bipolar disorder have been aided by the formation of a large-scale GWAS consortium: the Psychiatric Genomics Consortium (PGC). In contrast, only a handful of GWAS of PTSD have appeared in the literature to date. Here we describe the formation of a group dedicated to large-scale study of PTSD genetics: the PGC-PTSD. The PGC-PTSD faces challenges related to the contingency on trauma exposure and the large degree of ancestral genetic diversity within and across participating studies. Using the PGC analysis pipeline supplemented by analyses tailored to address these challenges, we anticipate that our first large-scale GWAS of PTSD will comprise over 10 000 cases and 30 000 trauma-exposed controls. Following in the footsteps of our PGC forerunners, this collaboration—of a scope that is unprecedented in the field of traumatic stress—will lead the search for replicable genetic associations and new insights into the biological underpinnings of PTSD. PMID:25904361

Evaluation of scanning 2D barcoded vaccines to improve data accuracy of vaccines administered.

PubMed

Daily, Ashley; Kennedy, Erin D; Fierro, Leslie A; Reed, Jenica Huddleston; Greene, Michael; Williams, Warren W; Evanson, Heather V; Cox, Regina; Koeppl, Patrick; Gerlach, Ken

2016-11-11

Accurately recording vaccine lot number, expiration date, and product identifiers, in patient records is an important step in improving supply chain management and patient safety in the event of a recall. These data are being encoded on two-dimensional (2D) barcodes on most vaccine vials and syringes. Using electronic vaccine administration records, we evaluated the accuracy of lot number and expiration date entered using 2D barcode scanning compared to traditional manual or drop-down list entry methods. We analyzed 128,573 electronic records of vaccines administered at 32 facilities. We compared the accuracy of records entered using 2D barcode scanning with those entered using traditional methods using chi-square tests and multilevel logistic regression. When 2D barcodes were scanned, lot number data accuracy was 1.8 percentage points higher (94.3-96.1%, P<0.001) and expiration date data accuracy was 11 percentage points higher (84.8-95.8%, P<0.001) compared with traditional methods. In multivariate analysis, lot number was more likely to be accurate (aOR=1.75; 99% CI, 1.57-1.96) as was expiration date (aOR=2.39; 99% CI, 2.12-2.68). When controlling for scanning and other factors, manufacturer, month vaccine was administered, and vaccine type were associated with variation in accuracy for both lot number and expiration date. Two-dimensional barcode scanning shows promise for improving data accuracy of vaccine lot number and expiration date records. Adapting systems to further integrate with 2D barcoding could help increase adoption of 2D barcode scanning technology. Published by Elsevier Ltd.

Testing Einstein's Gravity on Large Scales

NASA Technical Reports Server (NTRS)

Prescod-Weinstein, Chandra

2011-01-01

A little over a decade has passed since two teams studying high redshift Type Ia supernovae announced the discovery that the expansion of the universe was accelerating. After all this time, we?re still not sure how cosmic acceleration fits into the theory that tells us about the large-scale universe: General Relativity (GR). As part of our search for answers, we have been forced to question GR itself. But how will we test our ideas? We are fortunate enough to be entering the era of precision cosmology, where the standard model of gravity can be subjected to more rigorous testing. Various techniques will be employed over the next decade or two in the effort to better understand cosmic acceleration and the theory behind it. In this talk, I will describe cosmic acceleration, current proposals to explain it, and weak gravitational lensing, an observational effect that allows us to do the necessary precision cosmology.

Lessons learned from a review of the development of selected vaccines. National Vaccine Advisory Committee.

PubMed

Peter, G; des Vignes-Kendrick, M; Eickhoff, T C; Fine, A; Galvin, V; Levine, M M; Maldonado, Y A; Marcuse, E K; Monath, T P; Osborn, J E; Plotkin, S; Poland, G A; Quinlisk, M P; Smith, D R; Sokol, M; Soland, D B; Whitley-Williams, P N; Williamson, D E; Breiman, R F

1999-10-01

vaccine safety, immunogenicity, and efficacy; postlicensure measurements of the public health impact of the vaccine and a track record of the vaccine's safety and acceptance with large-scale use; and the critical need for international collaborations to evaluate vaccines against diseases of global importance that are rare in the United States (eg, typhoid fever). It was clear that the critical step-up from bench scale to pilot lots and then to large-scale production, which depends on a small group of highly trained individuals, is often a particularly vulnerable point in the development process. One fundamental lesson learned is that within the varied and comprehensive US vaccine development infrastructure, multiple and rather distinct paths can be followed to reach vaccine licensure. The National Vaccine Advisory Committee review process should be conducted periodically in the future to ascertain that the US vaccine development network, which has been enormously productive heretofore and has played a leadership role globally, is adapting appropriately to ensure that new, safe, and efficacious vaccines become available in a timely manner.

Vaccine Pipeline Has Grown During The Past Two Decades With More Early-Stage Trials From Small And Medium-Size Companies.

PubMed

Hwang, Thomas J; Kesselheim, Aaron S

2016-02-01

Many serious diseases lack safe and effective vaccines. Using a large commercial database, we examined trends in global vaccine research and development and found that the proportion of new vaccine candidates entering all stages of clinical development increased by 3-5 percentage points over the past two decades. Small and medium-size companies accounted for nearly twice as many new Phase I vaccine trials compared to large companies, but late-stage (Phase III) vaccine trials were dominated by large companies. There were no significant differences between vaccines and drugs in the probability of success in clinical trials or in profitability. Small and medium-size companies, including spin-outs from academic research centers, play an important role in innovative research and discovery. Our findings suggest that policy making targeted at smaller companies, such as prizes or opportunities for public-private partnerships, could support the development of new vaccines, particularly those targeting unmet medical needs and emerging public health threats. Project HOPE—The People-to-People Health Foundation, Inc.

Vaccines for viral and bacterial pathogens causing acute gastroenteritis: Part I: Overview, vaccines for enteric viruses and Vibrio cholerae.

PubMed

O'Ryan, Miguel; Vidal, Roberto; del Canto, Felipe; Salazar, Juan Carlos; Montero, David

2015-01-01

Efforts to develop vaccines for prevention of acute diarrhea have been going on for more than 40 y with partial success. The myriad of pathogens, more than 20, that have been identified as a cause of acute diarrhea throughout the years pose a significant challenge for selecting and further developing the most relevant vaccine candidates. Based on pathogen distribution as identified in epidemiological studies performed mostly in low-resource countries, rotavirus, Cryptosporidium, Shigella, diarrheogenic E. coli and V. cholerae are predominant, and thus the main targets for vaccine development and implementation. Vaccination against norovirus is most relevant in middle/high-income countries and possibly in resource-deprived countries, pending a more precise characterization of disease impact. Only a few licensed vaccines are currently available, of which rotavirus vaccines have been the most outstanding in demonstrating a significant impact in a short time period. This is a comprehensive review, divided into 2 articles, of nearly 50 vaccine candidates against the most relevant viral and bacterial pathogens that cause acute gastroenteritis. In order to facilitate reading, sections for each pathogen are organized as follows: i) a discussion of the main epidemiological and pathogenic features; and ii) a discussion of vaccines based on their stage of development, moving from current licensed vaccines to vaccines in advanced stage of development (in phase IIb or III trials) to vaccines in early stages of clinical development (in phase I/II) or preclinical development in animal models. In this first article we discuss rotavirus, norovirus and Vibrio cholerae. In the following article we will discuss Shigella, Salmonella (non-typhoidal), diarrheogenic E. coli (enterotoxigenic and enterohemorragic), and Campylobacter jejuni.

Vaccines for viral and bacterial pathogens causing acute gastroenteritis: Part I: Overview, vaccines for enteric viruses and Vibrio cholerae

PubMed Central

O’Ryan, Miguel; Vidal, Roberto; del Canto, Felipe; Salazar, Juan Carlos; Montero, David

2015-01-01

Efforts to develop vaccines for prevention of acute diarrhea have been going on for more than 40 y with partial success. The myriad of pathogens, more than 20, that have been identified as a cause of acute diarrhea throughout the years pose a significant challenge for selecting and further developing the most relevant vaccine candidates. Based on pathogen distribution as identified in epidemiological studies performed mostly in low-resource countries, rotavirus, Cryptosporidium, Shigella, diarrheogenic E. coli and V. cholerae are predominant, and thus the main targets for vaccine development and implementation. Vaccination against norovirus is most relevant in middle/high-income countries and possibly in resource-deprived countries, pending a more precise characterization of disease impact. Only a few licensed vaccines are currently available, of which rotavirus vaccines have been the most outstanding in demonstrating a significant impact in a short time period. This is a comprehensive review, divided into 2 articles, of nearly 50 vaccine candidates against the most relevant viral and bacterial pathogens that cause acute gastroenteritis. In order to facilitate reading, sections for each pathogen are organized as follows: i) a discussion of the main epidemiological and pathogenic features; and ii) a discussion of vaccines based on their stage of development, moving from current licensed vaccines to vaccines in advanced stage of development (in phase IIb or III trials) to vaccines in early stages of clinical development (in phase I/II) or preclinical development in animal models. In this first article we discuss rotavirus, norovirus and Vibrio cholerae. In the following article we will discuss Shigella, Salmonella (non-typhoidal), diarrheogenic E. coli (enterotoxigenic and enterohemorragic), and Campylobacter jejuni. PMID:25715048

Enteric glia.

PubMed

Rühl, A; Nasser, Y; Sharkey, K A

2004-04-01

The enteric nervous system is composed of both enteric neurones and enteric glia. Enteric glial cells were first described by Dogiel and are now known to outnumber neurones approximately 4 : 1. In the past, these cells were assumed to subserve a largely supportive role; however, recent evidence indicates that enteric glial cells may play a more active role in the control of gut function. In transgenic mouse models, where enteric glial cells are selectively ablated, the loss of glia results in intestinal inflammation and disruption of the epithelial barrier. Enteric glia are activated specifically by inflammatory insults and may contribute actively to inflammatory pathology via antigen presentation and cytokine synthesis. Enteric glia also express receptors for neurotransmitters and so may serve as intermediaries in enteric neurotransmission. Thus, enteric glia may serve as a link between the nervous and immune systems of the gut and may also have an important role in maintaining the integrity of the mucosal barrier and in other aspects of intestinal homeostasis.

Vaccines: the fourth century.

PubMed

Plotkin, Stanley A

2009-12-01

Vaccine development, which began with Edward Jenner's observations in the late 18th century, has entered its 4th century. From its beginnings, with the use of whole organisms that had been weakened or inactivated, to the modern-day use of genetic engineering, it has taken advantage of the tools discovered in other branches of microbiology. Numerous successful vaccines are in use, but the list of diseases for which vaccines do not exist is long. However, the multiplicity of strategies now available, discussed in this article, portends even more successful development of vaccines.

Prevention of childhood rotavirus disease through the use of Rotarix and RotaTeq vaccines.

PubMed

Lepage, Philippe; Vergison, Anne

2007-12-01

Rotaviruses are the most common enteric pathogens to cause acute diarrhoea in infants and young children throughout the world. Two new live, orally administered vaccines (Rotarix and RotaTeq) that provide protection against rotavirus infections are now available and have been licensed in many countries in Europe, North and Latin America. Two recent large clinical trials have demonstrated that their efficacy, immunogenicity and safety, including absence of vaccine-associated intussusception in young infants, are remarkably similar. The protection against severe rotavirus gastroenteritis extends into the second year of follow up for both vaccines. Rotarix and RotaTeq vaccines can be coadministered with routine childhood vaccines. However, more data on the efficacy of these two new vaccines in low-income nations are needed, particularly in Asia and Africa, before global inclusion of rotavirus vaccines into national immunisation programmes can be recommended.

Burden of vaccine preventable diseases at large events.

PubMed

Alqahtani, Amani S; Alfelali, Mohammad; Arbon, Paul; Booy, Robert; Rashid, Harunor

2015-11-27

Large events or mass gatherings (MGs) are known to amplify the risk of infectious diseases, many of which can be prevented by vaccination. In this review we have evaluated the burden of vaccine preventable diseases (VPDs) in MGs. Major databases like PubMed and Embase, Google Scholar and pertinent websites were searched by using MeSH terms and text words; this was supplemented by hand searching. Following data abstraction, the pooled estimate of the burden of VPDs was calculated when possible; otherwise a narrative synthesis was conducted. In the past, at religious MGs like Hajj and Kumbh Mela, cholera caused explosive outbreaks; but currently respiratory infections, notably influenza, are the commonest diseases not only at Hajj but also at World Youth Day and Winter Olympiad. The recent cumulative attack rate of influenza at Hajj is 8.7% (range 0.7-15.8%), and the cumulative prevalence is 3.6% (range: 0.3-38%). Small outbreaks of measles (13-42 cases per event) have been reported at sport, entertainment and religious events. A sizeable outbreak (>200 cases) was reported following a special Easter Festival in Austria. An outbreak of hepatitis A occurred following the 'Jam bands' music festival. Other VPDs including pneumococcal disease, pertussis and tuberculosis have been reported in relation to MG attendance. VPDs not only affect the participants of MGs but also their contacts; vaccine uptake is variable and vaccine implementation is likely to have beneficial effects. Research to address the knowledge gaps surrounding VPDs at MGs is needed. Copyright © 2015 Elsevier Ltd. All rights reserved.

Exploring and Promoting Prosocial Vaccination: A Cross-Cultural Experiment on Vaccination of Health Care Personnel

PubMed Central

Betsch, Cornelia; Korn, Lars; Holtmann, Cindy

2016-01-01

Influenza vaccination for health care personnel (HCP) is recommended particularly because it indirectly protects patients from contracting the disease. Vaccinating can therefore be interpreted as a prosocial act. However, HCP vaccination rates are often far too low to prevent nosocomial infections. Effective interventions are needed to increase HCP's influenza vaccine uptake. Here we devise a novel tool to experimentally test interventions that aim at increasing prosocially motivated vaccine uptake under controlled conditions. We conducted a large-scale and cross-cultural experiment with participants from countries with either a collectivistic (South Korea) or an individualistic (USA) cultural background. Results showed that prosocially motivated vaccination was more likely in South Korea compared to the US, mediated by a greater perception of vaccination as a social act. However, changing the default of vaccination, such that participants had to opt out rather than to opt in, increased vaccine uptake in the US and therefore compensated for the lower level of prosocial vaccination. In sum, the present study provides both a novel method to investigate HCP influenza vaccination behavior and interventions to increase their vaccine uptake. PMID:27725940

Exploring and Promoting Prosocial Vaccination: A Cross-Cultural Experiment on Vaccination of Health Care Personnel.

PubMed

Böhm, Robert; Betsch, Cornelia; Korn, Lars; Holtmann, Cindy

2016-01-01

Influenza vaccination for health care personnel (HCP) is recommended particularly because it indirectly protects patients from contracting the disease. Vaccinating can therefore be interpreted as a prosocial act. However, HCP vaccination rates are often far too low to prevent nosocomial infections. Effective interventions are needed to increase HCP's influenza vaccine uptake. Here we devise a novel tool to experimentally test interventions that aim at increasing prosocially motivated vaccine uptake under controlled conditions. We conducted a large-scale and cross-cultural experiment with participants from countries with either a collectivistic (South Korea) or an individualistic (USA) cultural background. Results showed that prosocially motivated vaccination was more likely in South Korea compared to the US, mediated by a greater perception of vaccination as a social act. However, changing the default of vaccination, such that participants had to opt out rather than to opt in, increased vaccine uptake in the US and therefore compensated for the lower level of prosocial vaccination. In sum, the present study provides both a novel method to investigate HCP influenza vaccination behavior and interventions to increase their vaccine uptake.

Energy transfers in large-scale and small-scale dynamos

NASA Astrophysics Data System (ADS)

Samtaney, Ravi; Kumar, Rohit; Verma, Mahendra

2015-11-01

We present the energy transfers, mainly energy fluxes and shell-to-shell energy transfers in small-scale dynamo (SSD) and large-scale dynamo (LSD) using numerical simulations of MHD turbulence for Pm = 20 (SSD) and for Pm = 0.2 on 10243 grid. For SSD, we demonstrate that the magnetic energy growth is caused by nonlocal energy transfers from the large-scale or forcing-scale velocity field to small-scale magnetic field. The peak of these energy transfers move towards lower wavenumbers as dynamo evolves, which is the reason for the growth of the magnetic fields at the large scales. The energy transfers U2U (velocity to velocity) and B2B (magnetic to magnetic) are forward and local. For LSD, we show that the magnetic energy growth takes place via energy transfers from large-scale velocity field to large-scale magnetic field. We observe forward U2U and B2B energy flux, similar to SSD.

Which Dengue Vaccine Approach Is the Most Promising, and Should We Be Concerned about Enhanced Disease after Vaccination? Questions Raised by the Development and Implementation of Dengue Vaccines: Example of the Sanofi Pasteur Tetravalent Dengue Vaccine.

PubMed

Guy, Bruno

2018-06-01

Dengue is a still-growing public health concern in many tropical and subtropical regions of the world. The development and implementation of an effective dengue vaccine in these regions is a high priority. This insight focuses on the expected characteristics of a safe and efficacious vaccine, referring to the clinical experience obtained during the development of the first tetravalent dengue vaccine from Sanofi Pasteur, now licensed in several endemic countries. Safety and efficacy data from both short- and long-term follow-up of large-scale efficacy studies will be discussed, as well as the next steps following vaccine introduction. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

Genetic stability of genome-scale deoptimized RNA virus vaccine candidates under selective pressure

PubMed Central

Le Nouën, Cyril; McCarty, Thomas; Brown, Michael; Smith, Melissa Laird; Lleras, Roberto; Dolan, Michael A.; Mehedi, Masfique; Yang, Lijuan; Luongo, Cindy; Liang, Bo; Munir, Shirin; DiNapoli, Joshua M.; Mueller, Steffen; Wimmer, Eckard; Collins, Peter L.; Buchholz, Ursula J.

2017-01-01

Recoding viral genomes by numerous synonymous but suboptimal substitutions provides live attenuated vaccine candidates. These vaccine candidates should have a low risk of deattenuation because of the many changes involved. However, their genetic stability under selective pressure is largely unknown. We evaluated phenotypic reversion of deoptimized human respiratory syncytial virus (RSV) vaccine candidates in the context of strong selective pressure. Codon pair deoptimized (CPD) versions of RSV were attenuated and temperature-sensitive. During serial passage at progressively increasing temperature, a CPD RSV containing 2,692 synonymous mutations in 9 of 11 ORFs did not lose temperature sensitivity, remained genetically stable, and was restricted at temperatures of 34 °C/35 °C and above. However, a CPD RSV containing 1,378 synonymous mutations solely in the polymerase L ORF quickly lost substantial attenuation. Comprehensive sequence analysis of virus populations identified many different potentially deattenuating mutations in the L ORF as well as, surprisingly, many appearing in other ORFs. Phenotypic analysis revealed that either of two competing mutations in the virus transcription antitermination factor M2-1, outside of the CPD area, substantially reversed defective transcription of the CPD L gene and substantially restored virus fitness in vitro and in case of one of these two mutations, also in vivo. Paradoxically, the introduction into Min L of one mutation each in the M2-1, N, P, and L proteins resulted in a virus with increased attenuation in vivo but increased immunogenicity. Thus, in addition to providing insights on the adaptability of genome-scale deoptimized RNA viruses, stability studies can yield improved synthetic RNA virus vaccine candidates. PMID:28049853

Large-scale Individual-based Models of Pandemic Influenza Mitigation Strategies

NASA Astrophysics Data System (ADS)

Kadau, Kai; Germann, Timothy; Longini, Ira; Macken, Catherine

2007-03-01

We have developed a large-scale stochastic simulation model to investigate the spread of a pandemic strain of influenza virus through the U.S. population of 281 million people, to assess the likely effectiveness of various potential intervention strategies including antiviral agents, vaccines, and modified social mobility (including school closure and travel restrictions) [1]. The heterogeneous population structure and mobility is based on available Census and Department of Transportation data where available. Our simulations demonstrate that, in a highly mobile population, restricting travel after an outbreak is detected is likely to delay slightly the time course of the outbreak without impacting the eventual number ill. For large basic reproductive numbers R0, we predict that multiple strategies in combination (involving both social and medical interventions) will be required to achieve a substantial reduction in illness rates. [1] T. C. Germann, K. Kadau, I. M. Longini, and C. A. Macken, Proc. Natl. Acad. Sci. (USA) 103, 5935-5940 (2006).

Rabies Vaccination: Higher Failure Rates in Imported Dogs than in those Vaccinated in Italy.

PubMed

Rota Nodari, E; Alonso, S; Mancin, M; De Nardi, M; Hudson-Cooke, S; Veggiato, C; Cattoli, G; De Benedictis, P

2017-03-01

The current European Union (EU) legislation decrees that pets entering the EU from a rabies-infected third country have to obtain a satisfactory virus-neutralizing antibody level, while those moving within the EU require only rabies vaccination as the risk of moving a rabid pet within the EU is considered negligible. A number of factors driving individual variations in dog vaccine response have been previously reported, including a high rate of vaccine failure in puppies, especially those subject to commercial transport. A total of 21 001 observations collected from dogs (2006-2012) vaccinated in compliance with the current EU regulations were statistically analysed to assess the effect of different risk factors related to rabies vaccine efficacy. Within this framework, we were able to compare the vaccination failure rate in a group of dogs entering the Italian border from EU and non-EU countries to those vaccinated in Italy prior to international travel. Our analysis identified that cross-breeds and two breed categories showed high vaccine success rates, while Beagles and Boxers were the least likely to show a successful response to vaccination (88.82% and 90.32%, respectively). Our analysis revealed diverse performances among the commercially available vaccines, in terms of serological peak windows, and marked differences according to geographical area. Of note, we found a higher vaccine failure rate in imported dogs (13.15%) than in those vaccinated in Italy (5.89%). Our findings suggest that the choice of vaccine may influence the likelihood of an animal achieving a protective serological level and that time from vaccination to sampling should be considered when interpreting serological results. A higher vaccine failure in imported compared to Italian dogs highlights the key role that border controls still have in assessing the full compliance of pet movements with EU legislation to minimize the risk of rabies being reintroduced into a disease-free area. �

A Recombinant Probiotic, Lactobacillus casei, Expressing the Clostridium perfringens α-toxoid, as an Orally Vaccine Candidate Against Gas Gangrene and Necrotic Enteritis.

PubMed

Alimolaei, Mojtaba; Golchin, Mehdi; Abshenas, Jalil; Ezatkhah, Majid; Bafti, Mehrdad Shamsaddini

2018-06-01

The alpha-toxin is one of the virulence factors of Clostridium perfringens for gas gangrene in humans and animals or necrotic enteritis in poultry. The C-terminal domain of this toxin ( cpa 247-370 ) was synthesized and cloned into pT1NX vector to construct the pT1NX-alpha plasmid. This surface-expressing plasmid was electroporated into Lactobacillus casei ATCC 393, generating the recombinant L. casei strain expressing alpha-toxoid (LC-α strain). Expression of this modified alpha-toxoid was confirmed by SDS-PAGE, immunoblotting, and direct immunofluorescence microscopy. BALB/c mice, immunized orally by the recombinant LC-α strain, elicited mucosal and significantly humoral immune responses (p < 0.05) and developed a protection against 900 MLD/mL of the standard alpha-toxin. This study showed that this recombinant LC-α strain could be a promising vaccine candidate against gas gangrene and necrotic enteritis.

Benefit-Cost Analysis of Foot-and-Mouth Disease Vaccination at the Farm-Level in South Vietnam.

PubMed

Truong, Dinh Bao; Goutard, Flavie Luce; Bertagnoli, Stéphane; Delabouglise, Alexis; Grosbois, Vladimir; Peyre, Marisa

2018-01-01

This study aimed to analyze the financial impact of foot-and-mouth disease (FMD) outbreaks in cattle at the farm-level and the benefit-cost ratio (BCR) of biannual vaccination strategy to prevent and eradicate FMD for cattle in South Vietnam. Production data were collected from 49 small-scale dairy farms, 15 large-scale dairy farms, and 249 beef farms of Long An and Tay Ninh province using a questionaire. Financial data of FMD impacts were collected using participatory tools in 37 villages of Long An province. The net present value, i.e., the difference between the benefits (additional revenue and saved costs) and costs (additional costs and revenue foregone), of FMD vaccination in large-scale dairy farms was 2.8 times higher than in small-scale dairy farms and 20 times higher than in beef farms. The BCR of FMD vaccination over 1 year in large-scale dairy farms, small-scale dairy farms, and beef farms were 11.6 [95% confidence interval (95% CI) 6.42-16.45], 9.93 (95% CI 3.45-16.47), and 3.02 (95% CI 0.76-7.19), respectively. The sensitivity analysis showed that varying the vaccination cost had more effect on the BCR of cattle vaccination than varying the market price. This benefit-cost analysis of biannual vaccination strategy showed that investment in FMD prevention can be financially profitable, and therefore sustainable, for dairy farmers. For beef cattle, it is less certain that vaccination is profitable. Additional benefit-cost analysis study of vaccination strategies at the national-level would be required to evaluate and adapt the national strategy to achieve eradication of this disease in Vietnam.

Scaling-up vaccine production: implementation aspects of a biomass growth observer and controller.

PubMed

Soons, Zita I T A; van den IJssel, Jan; van der Pol, Leo A; van Straten, Gerrit; van Boxtel, Anton J B

2009-04-01

This study considers two aspects of the implementation of a biomass growth observer and specific growth rate controller in scale-up from small- to pilot-scale bioreactors towards a feasible bulk production process for whole-cell vaccine against whooping cough. The first is the calculation of the oxygen uptake rate, the starting point for online monitoring and control of biomass growth, taking into account the dynamics in the gas-phase. Mixing effects and delays are caused by amongst others the headspace and tubing to the analyzer. These gas phase dynamics are modelled using knowledge of the system in order to reconstruct oxygen consumption. The second aspect is to evaluate performance of the monitoring and control system with the required modifications of the oxygen consumption calculation on pilot-scale. In pilot-scale fed-batch cultivation good monitoring and control performance is obtained enabling a doubled concentration of bulk vaccine compared to standard batch production.

Development of a scaled-down aerobic fermentation model for scale-up in recombinant protein vaccine manufacturing.

PubMed

Farrell, Patrick; Sun, Jacob; Gao, Meg; Sun, Hong; Pattara, Ben; Zeiser, Arno; D'Amore, Tony

2012-08-17

A simple approach to the development of an aerobic scaled-down fermentation model is presented to obtain more consistent process performance during the scale-up of recombinant protein manufacture. Using a constant volumetric oxygen mass transfer coefficient (k(L)a) for the criterion of a scale-down process, the scaled-down model can be "tuned" to match the k(L)a of any larger-scale target by varying the impeller rotational speed. This approach is demonstrated for a protein vaccine candidate expressed in recombinant Escherichia coli, where process performance is shown to be consistent among 2-L, 20-L, and 200-L scales. An empirical correlation for k(L)a has also been employed to extrapolate to larger manufacturing scales. Copyright © 2012 Elsevier Ltd. All rights reserved.

Genome-derived vaccines.

PubMed

De Groot, Anne S; Rappuoli, Rino

2004-02-01

Vaccine research entered a new era when the complete genome of a pathogenic bacterium was published in 1995. Since then, more than 97 bacterial pathogens have been sequenced and at least 110 additional projects are now in progress. Genome sequencing has also dramatically accelerated: high-throughput facilities can draft the sequence of an entire microbe (two to four megabases) in 1 to 2 days. Vaccine developers are using microarrays, immunoinformatics, proteomics and high-throughput immunology assays to reduce the truly unmanageable volume of information available in genome databases to a manageable size. Vaccines composed by novel antigens discovered from genome mining are already in clinical trials. Within 5 years we can expect to see a novel class of vaccines composed by genome-predicted, assembled and engineered T- and Bcell epitopes. This article addresses the convergence of three forces--microbial genome sequencing, computational immunology and new vaccine technologies--that are shifting genome mining for vaccines onto the forefront of immunology research.

Effect of Salmonella vaccination of breeder chickens on contamination of broiler chicken carcasses in integrated poultry operations.

PubMed

Dórea, Fernanda C; Cole, Dana J; Hofacre, Charles; Zamperini, Katherine; Mathis, Demetrius; Doyle, Michael P; Lee, Margie D; Maurer, John J

2010-12-01

While measures to control carcass contamination with Salmonella at the processing plant have been implemented with some success, on-farm interventions that reduce Salmonella prevalence in meat birds entering the processing plant have not translated well on a commercial scale. We determined the impact of Salmonella vaccination on commercial poultry operations by monitoring four vaccinated and four nonvaccinated breeder (parental) chicken flocks and comparing Salmonella prevalences in these flocks and their broiler, meat bird progeny. For one poultry company, their young breeders were vaccinated by using a live-attenuated Salmonella enterica serovar Typhimurium vaccine (Megan VAC-1) followed by a killed Salmonella bacterin consisting of S. enterica serovar Berta and S. enterica serovar Kentucky. The other participating poultry company did not vaccinate their breeders or broilers. The analysis revealed that vaccinated hens had a lower prevalence of Salmonella in the ceca (38.3% versus 64.2%; P < 0.001) and the reproductive tracts (14.22% versus 51.7%; P < 0.001). We also observed a lower Salmonella prevalence in broiler chicks (18.1% versus 33.5%; P < 0.001), acquired from vaccinated breeders, when placed at the broiler farms contracted with the poultry company. Broiler chicken farms populated with chicks from vaccinated breeders also tended to have fewer environmental samples containing Salmonella (14.4% versus 30.1%; P < 0.001). There was a lower Salmonella prevalence in broilers entering the processing plants (23.4% versus 33.5%; P < 0.001) for the poultry company that utilized this Salmonella vaccination program for its breeders. Investigation of other company-associated factors did not indicate that the difference between companies could be attributed to measures other than the vaccination program.

Vaccines and vaccination against yellow fever: WHO Position Paper, June 2013--recommendations.

PubMed

2015-01-01

This article presents the World Health Organizations (WHO) evidence and recommendations for the use of yellow fever (YF) vaccination from "Vaccines and vaccination against yellow fever: WHO Position Paper - June 2013" published in the Weekly Epidemiological Record. This position paper summarizes the WHO position on the use of YF vaccination, in particular that a single dose of YF vaccine is sufficient to confer sustained life-long protective immunity against YF disease. A booster dose is not necessary. The current document replaces the position paper on the use of yellow fever vaccines and vaccination published in 2003. Footnotes to this paper provide a number of core references. In accordance with its mandate to provide guidance to Member States on health policy matters, WHO issues a series of regularly updated position papers on vaccines and combinations of vaccines against diseases that have an international public health impact. These papers are concerned primarily with the use of vaccines in large-scale immunization programmes; they summarize essential background information on diseases and vaccines, and conclude with WHO's current position on the use of vaccines in the global context. This paper reflects the recommendations of WHO's Strategic Advisory Group of Experts (SAGE) on immunization. These recommendations were discussed by SAGE at its April 2013 meeting. Evidence presented at the meeting can be accessed at http://www.who.int/immunization/sage/previous/en/index.html. Copyright © 2014. Published by Elsevier Ltd.

On the scaling of small-scale jet noise to large scale

NASA Technical Reports Server (NTRS)

Soderman, Paul T.; Allen, Christopher S.

1992-01-01

An examination was made of several published jet noise studies for the purpose of evaluating scale effects important to the simulation of jet aeroacoustics. Several studies confirmed that small conical jets, one as small as 59 mm diameter, could be used to correctly simulate the overall or PNL noise of large jets dominated by mixing noise. However, the detailed acoustic spectra of large jets are more difficult to simulate because of the lack of broad-band turbulence spectra in small jets. One study indicated that a jet Reynolds number of 5 x 10 exp 6 based on exhaust diameter enabled the generation of broad-band noise representative of large jet mixing noise. Jet suppressor aeroacoustics is even more difficult to simulate at small scale because of the small mixer nozzles with flows sensitive to Reynolds number. Likewise, one study showed incorrect ejector mixing and entrainment using small-scale, short ejector that led to poor acoustic scaling. Conversely, fairly good results were found with a longer ejector and, in a different study, with a 32-chute suppressor nozzle. Finally, it was found that small-scale aeroacoustic resonance produced by jets impacting ground boards does not reproduce at large scale.

What maintains parental support for vaccination when challenged by anti-vaccination messages? A qualitative study.

PubMed

Leask, Julie; Chapman, Simon; Hawe, Penelope; Burgess, Margaret

2006-11-30

This study sought to explore how parents respond to competing media messages about vaccine safety. Six focus groups with mothers of infants were shown television vignettes of typical pro- and anti-vaccination claims. Thematic analysis of transcripts was undertaken. Mothers expressed surprise and concern about alleged vaccine risks but quickly reinstated their support for vaccination by deference to authority figures; type-casting immunisation opponents; and notions of anticipatory regret, good parenting and social responsibility. We conclude that personal experiences, value systems and level of trust in health professionals are fundamental to parental decision making about vaccination. Vaccination advocacy should increase the focus on matters of process such as maintaining trust and public confidence, particularly in health professionals. Stories about people affected by vaccine-preventable diseases need to re-enter the public discourse.

Seasonal vaccination against malaria: a potential use for an imperfect malaria vaccine.

PubMed

Greenwood, Brian; Dicko, Alassane; Sagara, Issaka; Zongo, Issaka; Tinto, Halidou; Cairns, Matthew; Kuepfer, Irene; Milligan, Paul; Ouedraogo, Jean-Bosco; Doumbo, Ogobara; Chandramohan, Daniel

2017-05-02

In many parts of the African Sahel and sub-Sahel, where malaria remains a major cause of mortality and morbidity, transmission of the infection is highly seasonal. Seasonal malaria chemoprevention (SMC), which involves administration of a full course of malaria treatment to young children at monthly intervals during the high transmission season, is proving to be an effective malaria control measure in these areas. However, SMC does not provide complete protection and it is demanding to deliver for both families and healthcare givers. Furthermore, there is a risk of the emergence in the future of resistance to the drugs, sulfadoxine-pyrimethamine and amodiaquine, that are currently being used for SMC. Substantial progress has been made in the development of malaria vaccines during the past decade and one malaria vaccine, RTS,S/AS01, has received a positive opinion from the European Medicines Authority and will soon be deployed in large-scale, pilot implementation projects in sub-Saharan Africa. A characteristic feature of this vaccine, and potentially of some of the other malaria vaccines under development, is that they provide a high level of efficacy during the period immediately after vaccination, but that this wanes rapidly, perhaps because it is difficult to develop effective immunological memory to malaria antigens in subjects exposed previously to malaria infection. A potentially effective way of using malaria vaccines with high initial efficacy but which provide only a short period of protection could be annual, mass vaccination campaigns shortly before each malaria transmission season in areas where malaria transmission is confined largely to a few months of the year.

Introducing Vi polysaccharide typhoid fever vaccine to primary school children in North Jakarta, Indonesia, via an existent school-based vaccination platform.

PubMed

Agtini, M D; Ochiai, R L; Soeharno, R; Lee, H J; Sundoro, J; Hadinegoro, S R; Han, O P; Tana, L; Halim, F X S; Ghani, L; Delima; Lestari, W; Sintawati, F X; Kusumawardani, N; Malik, R; Santoso, T S; Nadjib, M; Soeroso, S; Wangsasaputra, F; Ali, M; Ivanoff, B; Galindo, C M; Pang, T; Clemens, J D; Suwandono, A; Acosta, C J

2006-11-01

To report results on coverage, safety and logistics of a large-scale, school-based Vi polysaccharide immunization campaign in North Jakarta. Of 443 primary schools in North Jakarta, Indonesia, 18 public schools were randomly selected for this study. Exclusion criteria were fever 37.5 degrees C or higher at the time of vaccination or a known history of hypersensitivity to any vaccine. Adverse events were monitored and recorded for 1 month after immunization. Because this was a pilot programme, resource use was tracked in detail. During the February 2004 vaccination campaign, 4828 students were immunized (91% of the target population); another 394 students (7%) were vaccinated during mop-up programmes. Informed consent was obtained for 98% of the target population. In all, 34 adverse events were reported, corresponding to seven events per 1000 doses injected; none was serious. The manufacturer recommended cold chain was maintained throughout the programme. This demonstration project in two sub-districts of North Jakarta shows that a large-scale, school-based typhoid fever Vi polysaccharide vaccination campaign is logistically feasible, safe and minimally disruptive to regular school activities, when used in the context of an existing successful immunization platform. The project had high parental acceptance. Nonetheless, policy-relevant questions still need to be answered before implementing a widespread Vi polysaccharide vaccine programme in Indonesia.

Whooping cough, twenty years from acellular vaccines introduction.

PubMed

Greco, D; Esposito, S; Tozzi, A; Pandolfi, E; Icardi, G; Giammanco, A

2015-01-01

Clinical pertussis resulting from infection with B. pertussis is a significant medical and public health problem, despite the huge success of vaccination that has greatly reduced its incidence. The whole cell vaccine had an undeniable success over the last 50 years, but its acceptance was strongly inhibited by fear, only partially justified, of severe side effects, but also, in the Western world, by the difficulty to enter in combination with other vaccines: today multi-vaccine formulations are essential to maintain a high vaccination coverage. The advent of acellular vaccines was greeted with enthusiasm by the public health world: in the Nineties, several controlled vaccine trials were carried out: they demonstrated a high safety and good efficacy of new vaccines. In fact, in the Western world, the acellular vaccines completely replaced the whole cells ones. In the last years, ample evidence on the variety of protection of these vaccines linked to the presence of different antigens of Bordetella pertussis was collected. It also became clear that the protection provided, on average around 80%, leaves every year a significant cohort of vaccinated susceptible even in countries with a vaccination coverage of 95%, such as Italy. Finally, it was shown that, as for the pertussis disease, protection decreases over time, to leave a proportion of adolescents and adults unprotected. Waiting for improved pertussis vaccines, the disease control today requires a different strategy that includes a booster at 5 years for infants, but also boosters for teenagers and young adults, re-vaccination of health care personnel, and possibly of pregnant women and of those who are in contact with infants (cocooning). Finally, the quest for better vaccines inevitably tends towards pertussis acellular vaccines with at least three components, which have demonstrated superior effectiveness and have been largely in use in Italy for fifteen years.

Large-Scale Disasters

NASA Astrophysics Data System (ADS)

Gad-El-Hak, Mohamed

"Extreme" events - including climatic events, such as hurricanes, tornadoes, and drought - can cause massive disruption to society, including large death tolls and property damage in the billions of dollars. Events in recent years have shown the importance of being prepared and that countries need to work together to help alleviate the resulting pain and suffering. This volume presents a review of the broad research field of large-scale disasters. It establishes a common framework for predicting, controlling and managing both manmade and natural disasters. There is a particular focus on events caused by weather and climate change. Other topics include air pollution, tsunamis, disaster modeling, the use of remote sensing and the logistics of disaster management. It will appeal to scientists, engineers, first responders and health-care professionals, in addition to graduate students and researchers who have an interest in the prediction, prevention or mitigation of large-scale disasters.

The global fight to develop antipoverty vaccines in the anti-vaccine era.

PubMed

Hotez, Peter J

2018-02-02

Antipoverty vaccines are the vaccines targeting a group of approximately 20 neglected tropical diseases (NTDs), as currently defined by the World Health Organization (WHO). The "antipoverty" moniker refers to the fact that NTDs trap populations in poverty due to their chronic and deleterious effects on child intellect and worker productivity. Therefore, NTD vaccines can be expected to promote both global health and economic advancement. Unfortunately, antipoverty vaccine development has lagged behind vaccines for major childhood infections and pandemic threats, despite evidence for their cost-effectiveness and cost-savings. Currently, the only licensed vaccines for NTDs include those for yellow fever, dengue, and rabies, although several other NTD vaccines for hookworm disease, schistosomiasis, leishmaniasis, and Zika and Ebola virus infections are in different stages of clinical development, while others are at the preclinical development stage. With the exception of the viral NTD vaccines there so far has been minimal industry interest in the antipoverty vaccines, leaving their development to a handful of non-profit product development partnerships. The major scientific and geopolitical hurdles to antipoverty vaccine development are discussed, including a rising antivaccine ("antivax") movement now entering highly populated low- and middle-income countries.

High stability of yellow fever 17D-204 vaccine: a 12-year restrospective analysis of large-scale production.

PubMed

Barban, V; Girerd, Y; Aguirre, M; Gulia, S; Pétiard, F; Riou, P; Barrere, B; Lang, J

2007-04-12

We have retrospectively analyzed 12 bulk lots of yellow fever vaccine Stamaril, produced between 1990 and 2002 and prepared from the same seed lot that has been in continuous use since 1990. All vaccine batches displayed identical genome sequence. Only four nucleotide substitutions were observed, compared to previously published sequence, with no incidence at amino-acid level. Fine analysis of viral plaque size distribution was used as an additional marker for genetic stability and demonstrated a remarkable homogeneity of the viral population. The total virus load, measured by qRT-PCR, was also homogeneous pointing out reproducibility of the vaccine production process. Mice inoculated intracerebrally with the different bulks exhibited a similar average survival time, and ratio between in vitro potency and mouse LD(50) titers remained constant from batch-to-batch. Taken together, these data demonstrate the genetic stability of the strain at mass production level over a period of 12 years and reinforce the generally admitted idea of the safety of YF17D-based vaccines.

On the scaling of small-scale jet noise to large scale

NASA Technical Reports Server (NTRS)

Soderman, Paul T.; Allen, Christopher S.

1992-01-01

An examination was made of several published jet noise studies for the purpose of evaluating scale effects important to the simulation of jet aeroacoustics. Several studies confirmed that small conical jets, one as small as 59 mm diameter, could be used to correctly simulate the overall or perceived noise level (PNL) noise of large jets dominated by mixing noise. However, the detailed acoustic spectra of large jets are more difficult to simulate because of the lack of broad-band turbulence spectra in small jets. One study indicated that a jet Reynolds number of 5 x 10(exp 6) based on exhaust diameter enabled the generation of broad-band noise representative of large jet mixing noise. Jet suppressor aeroacoustics is even more difficult to simulate at small scale because of the small mixer nozzles with flows sensitive to Reynolds number. Likewise, one study showed incorrect ejector mixing and entrainment using a small-scale, short ejector that led to poor acoustic scaling. Conversely, fairly good results were found with a longer ejector and, in a different study, with a 32-chute suppressor nozzle. Finally, it was found that small-scale aeroacoustic resonance produced by jets impacting ground boards does not reproduce at large scale.

Large scale survey of enteric viruses in river and waste water underlines the health status of the local population.

PubMed

Prevost, B; Lucas, F S; Goncalves, A; Richard, F; Moulin, L; Wurtzer, S

2015-06-01

Although enteric viruses constitute a major cause of acute waterborne diseases worldwide, environmental data about occurrence and viral load of enteric viruses in water are not often available. In this study, enteric viruses (i.e., adenovirus, aichivirus, astrovirus, cosavirus, enterovirus, hepatitis A and E viruses, norovirus of genogroups I and II, rotavirus A and salivirus) were monitored in the Seine River and the origin of contamination was untangled. A total of 275 water samples were collected, twice a month for one year, from the river Seine, its tributaries and the major WWTP effluents in the Paris agglomeration. All water samples were negative for hepatitis A and E viruses. AdV, NVGI, NVGII and RV-A were the most prevalent and abundant populations in all water samples. The viral load and the detection frequency increased significantly between the samples collected the most upstream and the most downstream of the Paris urban area. The calculated viral fluxes demonstrated clearly the measurable impact of WWTP effluents on the viral contamination of the Seine River. The viral load was seasonal for almost all enteric viruses, in accordance with the gastroenteritis recordings provided by the French medical authorities. These results implied the existence of a close relationship between the health status of inhabitants and the viral contamination of WWTP effluents and consequently surface water contamination. Subsequently, the regular analysis of wastewater could serve as a proxy for the monitoring of the human viruses circulating in both a population and surface water. Copyright © 2015. Published by Elsevier Ltd.

A field trial, of preshipment vaccination, with intranasal infectious bovine rhinotracheitis-parainfluenza-3 vaccines.

PubMed Central

Martin, W; Willson, P; Curtis, R; Allen, B; Acres, S

1983-01-01

A total of 849 calves, 278 controls, 335 vaccinated intranasally with IBR-PI3/TS and 236 vaccinated intranasally with IBR-PI3/PTC were studied in a field trial of preimmunization. All calves were vaccinated in Saskatchewan at least three weeks prior to shipment to feedlots. Four hundred and twenty six calves were not sold within eight weeks of vaccination; however, seven of these died within four weeks of vaccination. Treatment rates varied from 1.0% to 5.2%. There was no significant effect of vaccination on treatment rates. Similarly, there was no significant effect of vaccination in the 74 calves sold to feedlots in Saskatchewan. Three hundred and forty nine calves were sold to feedlots in Ontario. Two of these died from fibrinous pneumonia. Treatment rates varied from 1.7% to 33.3% in different feedlots, but there was no significant effect of vaccination on treatment rates. Therefore, preimmunization is unlikely to significantly reduce the overall treatment rate in calves entering feedlots. PMID:6315194

Large-scale structural optimization

NASA Technical Reports Server (NTRS)

Sobieszczanski-Sobieski, J.

1983-01-01

Problems encountered by aerospace designers in attempting to optimize whole aircraft are discussed, along with possible solutions. Large scale optimization, as opposed to component-by-component optimization, is hindered by computational costs, software inflexibility, concentration on a single, rather than trade-off, design methodology and the incompatibility of large-scale optimization with single program, single computer methods. The software problem can be approached by placing the full analysis outside of the optimization loop. Full analysis is then performed only periodically. Problem-dependent software can be removed from the generic code using a systems programming technique, and then embody the definitions of design variables, objective function and design constraints. Trade-off algorithms can be used at the design points to obtain quantitative answers. Finally, decomposing the large-scale problem into independent subproblems allows systematic optimization of the problems by an organization of people and machines.

Vaccine supply: a cross-national perspective.

PubMed

Danzon, Patricia M; Pereira, Nuno Sousa; Tejwani, Sapna S

2005-01-01

In U.S. vaccine markets, competing producers with high fixed, sunk costs face relatively concentrated demand. This tends to lead to exit of all but one or very few producers per vaccine. Detailed evidence of exits and shortages in the flu vaccine market demonstrates the importance of high fixed costs, demand uncertainty, and dynamic quality competition. A comparison of vaccine suppliers in four industrialized countries compared with the United States shows that smaller foreign markets often have more and different vaccine suppliers. High, country-specific, fixed costs, combined with price and volume uncertainty, plausibly deters these potential suppliers from attempting to enter the U.S. market.

Commercialization of veterinary viral vaccines.

PubMed

Flore, P H

2004-12-01

If vaccines are to reliably prevent disease, they must be developed, produced and quality-controlled according to very strict regulations and procedures. Veterinary viral vaccine registrations are governed by different rules in different countries, but these rules all emphasize that the quality of the raw materials--the cells, eggs, animals or plants that are used in production--need to be carefully controlled. The veterinary vaccine business is also very cost-conscious. Emphasis over the last 5-10 years has therefore been to develop culture systems that minimize labor and sterility problems and thus provide for reliable and cost-effective production. Implementing these often more complex systems in a production environment takes considerable effort, first in scale-up trials and further down the line in convincing production personnel to change their familiar system for something new and possibly untried. To complete scale-up trials successfully, it is absolutely necessary to understand the biochemistry of the cells and the influence of the virus on the cells under scale-up and later production conditions. Once a viral product can be produced on a large scale, it is imperative that the quality of the end-product is controlled in an intelligent way. One needs to know whether the end-product performs in the animal as was intended during its conception in the research and development department. The development of the appropriate tests to demonstrate this plays an important role in the successful development of a vaccine.

Vaccines for fish in aquaculture.

PubMed

Sommerset, Ingunn; Krossøy, Bjørn; Biering, Eirik; Frost, Petter

2005-02-01

Vaccination plays an important role in large-scale commercial fish farming and has been a key reason for the success of salmon cultivation. In addition to salmon and trout, commercial vaccines are available for channel catfish, European seabass and seabream, Japanese amberjack and yellowtail, tilapia and Atlantic cod. In general, empirically developed vaccines based on inactivated bacterial pathogens have proven to be very efficacious in fish. Fewer commercially available viral vaccines and no parasite vaccines exist. Substantial efficacy data are available for new fish vaccines and advanced technology has been implemented. However, before such vaccines can be successfully commercialized, several hurdles have to be overcome regarding the production of cheap but effective antigens and adjuvants, while bearing in mind environmental and associated regulatory concerns (e.g., those that limit the use of live vaccines). Pharmaceutical companies have performed a considerable amount of research on fish vaccines, however, limited information is available in scientific publications. In addition, salmonids dominate both the literature and commercial focus, despite their relatively small contribution to the total volume of farmed fish in the world. This review provides an overview of the fish vaccines that are currently commercially available and some viewpoints on how the field is likely to evolve in the near future.

Large Scale Metal Additive Techniques Review

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

Nycz, Andrzej; Adediran, Adeola I; Noakes, Mark W

2016-01-01

In recent years additive manufacturing made long strides toward becoming a main stream production technology. Particularly strong progress has been made in large-scale polymer deposition. However, large scale metal additive has not yet reached parity with large scale polymer. This paper is a review study of the metal additive techniques in the context of building large structures. Current commercial devices are capable of printing metal parts on the order of several cubic feet compared to hundreds of cubic feet for the polymer side. In order to follow the polymer progress path several factors are considered: potential to scale, economy, environmentmore » friendliness, material properties, feedstock availability, robustness of the process, quality and accuracy, potential for defects, and post processing as well as potential applications. This paper focuses on current state of art of large scale metal additive technology with a focus on expanding the geometric limits.« less

Vaccine manufacturing and technology: from biotechnological platforms to syntethic epitopes, current viepoint.

PubMed

Ignateva, G A

2016-01-01

The Purposes: the review take into account short history of vaccination practice and development of vaccine technology. In the review we include data from several monographs about manufacturing of vaccines published by authors from such companies as Merck & Co; Sanofi Pasteur; Dynavax Europe/Rhein Biotech GmbH; Latham Biopharm Group; Aridis Pharmaceuticals LLC; Genentech; Amgen; Shamir Biologics LLC; Biopharm Services US; Novartis Pharma AG, аnd several research centers: Laboratory of Bacterial Polysaccharides, Center for Biologics Evaluation and Research; Purdue University, West Lafayette, IN, US; Department of Pharmaceutical Chemistry, Univ. Of Kansas; Max Planck Institute for dynamics of Complex Technical Systems; Fraunhofer USA Center for Molecular Biotechnology; US Dep. of Agriculture Animal and Plant Health Inspection Service, etc. In historic literature there are data about inoculation practices in antique China, Persia, India, Byzantium, native Americans, some African population. In modern immunology since the end of XIX century the vaccines were produced at the in vivo platforms - in animals (rabbits, mice, cows). Since 1931 due to E. Goodpasture' elaboration most virus vaccines were and are produced at the in ovo platform. In 1949 J.F. Enders elaborated large-scale polio virus production in the primary culture of monkey kidney cells in vitro. Up to day primary culture of chiken embrio fibroblasts are used to large-scale production of vaccine viruses of measles, mumps, rabies. Since 2000-th in Western countries most part of virus vaccines were began to produced via a cultivation in continuous tumor cell lines. The last technology is the most low cost for large-scale production of vaccines. We review several new biotechnological platforms for the production of the recombinant protein or virus-like particles as subunit vaccines: plant system, algae, mushrooms, insect cells, etc. Beside of good purpose of vaccination - prophylactic of several infectious

The Yellow Fever Vaccine: A History

PubMed Central

Frierson, J. Gordon

2010-01-01

After failed attempts at producing bacteria-based vaccines, the discovery of a viral agent causing yellow fever and its isolation in monkeys opened new avenues of research. Subsequent advances were the attenuation of the virus in mice and later in tissue culture; the creation of the seed lot system to avoid spontaneous mutations; the ability to produce the vaccine on a large scale in eggs; and the removal of dangerous contaminants. An important person in the story is Max Theiler, who was Professor of Epidemiology and Public Health at Yale from 1964-67, and whose work on virus attenuation created the modern vaccine and earned him the Nobel Prize. PMID:20589188

Putative vaccine breakthrough event associated with heterotypic rotavirus infection in newborn calves, Turkey, 2015.

PubMed

Karayel, Ilke; Fehér, Enikő; Marton, Szilvia; Coskun, Nüvit; Bányai, Krisztián; Alkan, Feray

2017-03-01

Group A rotaviruses (RVA) are regarded as major enteric pathogens of large ruminants, including cattle. Rotavirus vaccines administered to pregnant cows are commonly used to provide passive immunity that protects newborn calves from the clinical disease. In this study we report the detection of RVA from calves with severe diarrhea in a herd regularly vaccinated to prevent enteric infections including RVA. Diarrheic disease was observed in newborn calves aged 4-15days, with high morbidity and mortality rates, but no diarrhea was seen in adult animals. Rotavirus antigen was detected by enzyme-immunoassay in the intestinal content or the fecal samples of all examined animals. Besides RVA, bovine coronavirus and bovine enteric calicivirus were detected in some samples. Selected RVA strains were characterized by whole genome sequencing. Two strains, RVA/Cow-wt/TUR/Amasya-1/2015/G8P[5] and RVA/Cow-wt/TUR/Amasya-2/2015/G8P[5] were genotyped as G8-P[5]-I2-R2-C2-M2-A3-N2-T6-E2-H3 and showed >99% nucleotide sequence identity among themselves. This genomic constellation is fairly common among bovine RVA strains; however, phylogenetic analysis of the G8 VP7 gene showed close genetic relationship to some European human RVA strains (up to 98.4% nt identity). Our findings is the first indication regarding the circulation of G8 RVA strains in Turkey. Given that the administered RVA vaccines contained type G6 and G10 VP7 antigens some concerns raised with regard to the level of heterotypic protection elicited by the vaccine strains against circulating bovine G8 RVA strains. Enhancement of surveillance of circulating RVA strains in calves across Turkey is needed to support ongoing vaccination programs. Copyright © 2016 Elsevier B.V. All rights reserved.

Skin Friction Reduction Through Large-Scale Forcing

NASA Astrophysics Data System (ADS)

Bhatt, Shibani; Artham, Sravan; Gnanamanickam, Ebenezer

2017-11-01

Flow structures in a turbulent boundary layer larger than an integral length scale (δ), referred to as large-scales, interact with the finer scales in a non-linear manner. By targeting these large-scales and exploiting this non-linear interaction wall shear stress (WSS) reduction of over 10% has been achieved. The plane wall jet (PWJ), a boundary layer which has highly energetic large-scales that become turbulent independent of the near-wall finer scales, is the chosen model flow field. It's unique configuration allows for the independent control of the large-scales through acoustic forcing. Perturbation wavelengths from about 1 δ to 14 δ were considered with a reduction in WSS for all wavelengths considered. This reduction, over a large subset of the wavelengths, scales with both inner and outer variables indicating a mixed scaling to the underlying physics, while also showing dependence on the PWJ global properties. A triple decomposition of the velocity fields shows an increase in coherence due to forcing with a clear organization of the small scale turbulence with respect to the introduced large-scale. The maximum reduction in WSS occurs when the introduced large-scale acts in a manner so as to reduce the turbulent activity in the very near wall region. This material is based upon work supported by the Air Force Office of Scientific Research under Award Number FA9550-16-1-0194 monitored by Dr. Douglas Smith.

Incorporating economies of scale in the cost estimation in economic evaluation of PCV and HPV vaccination programmes in the Philippines: a game changer?

PubMed

Suwanthawornkul, Thanthima; Praditsitthikorn, Naiyana; Kulpeng, Wantanee; Haasis, Manuel Alexander; Guerrero, Anna Melissa; Teerawattananon, Yot

2018-01-01

Many economic evaluations ignore economies of scale in their cost estimation, which means that cost parameters are assumed to have a linear relationship with the level of production. Economies of scale is the situation when the average total cost of producing a product decreases with increasing volume caused by reducing the variable costs due to more efficient operation. This study investigates the significance of applying the economies of scale concept: the saving in costs gained by an increased level of production in economic evaluation of pneumococcal conjugate vaccines (PCV) and human papillomavirus (HPV) vaccinations. The fixed and variable costs of providing partial (20% coverage) and universal (100% coverage) vaccination programs in the Philippines were estimated using various methods, including costs of conducting questionnaire survey, focus-group discussion, and analysis of secondary data. Costing parameters were utilised as inputs for the two economic evaluation models for PCV and HPV. Incremental cost-effectiveness ratios (ICERs) and 5-year budget impacts with and without applying economies of scale to the costing parameters for partial and universal coverage were compared in order to determine the effect of these different costing approaches. The program costs of the partial coverage for the two immunisation programs were not very different when applying and not applying the economies of scale concept. Nevertheless, the program costs for universal coverage were 0.26 and 0.32 times lower when applying economies of scale compared to not applying economies of scale for the pneumococcal and human papillomavirus vaccinations, respectively. ICERs varied by up to 98% for pneumococcal vaccinations, whereas the change in ICERs in the human papillomavirus vaccination depended on both the costs of cervical cancer screening and the vaccination program. This results in a significant difference in the 5-year budget impact, accounting for 30 and 40% of reduction in

Status of vaccine research and development of vaccines for malaria.

PubMed

Birkett, Ashley J

2016-06-03

Despite recent progress in reducing deaths attributable to malaria, it continues to claim approximately 500,000 lives per year and is associated with approximately 200 million infections. New tools, including safe and effective vaccines, are needed to ensure that the gains of the last 15 years are leveraged toward achieving the ultimate goal of malaria parasite eradication. In 2015, the European Medicines Agency announced the adoption of a positive opinion for the malaria vaccine candidate most advanced in development, RTS,S/AS01, which provides modest protection against clinical malaria; in early 2016, WHO recommended large-scale pilot implementations of RTS,S in settings of moderate-to-high malaria transmission. In alignment with these advancements, the community goals and preferred product characteristics for next-generation vaccines have been updated to inform the development of vaccines that are highly efficacious in preventing clinical malaria, and those needed to accelerate parasite elimination. Next-generation vaccines, targeting all stages of the parasite lifecycle, are in early-stage development with the most advanced in Phase 2 trials. Importantly, progress is being made in the definition of feasible regulatory pathways to accelerate timelines, including for vaccines designed to interrupt transmission of parasites from humans to mosquitoes. The continued absence of financially lucrative, high-income markets to drive investment in malaria vaccine development points to continued heavy reliance on public and philanthropic funding. Copyright © 2016 World Health Organization. Published by Elsevier Ltd.. All rights reserved.

Enteric Immunization of Mice Against Influenza with Recombinant Vaccinia

NASA Astrophysics Data System (ADS)

Meitin, Catherine A.; Bender, Bradley S.; Small, Parker A., Jr.

1994-11-01

Intrajejunal administration to mice of a recombinant vaccinia virus containing the influenza virus hemagglutinin gene induced IgA antibody in nasal, gut, and vaginal secretions. It also induced IgG antibody in serum and cell-mediated immunity. The immunization provided significant protection against an influenza virus challenge. This work suggests that enteric-coated recombinant vaccinia could be an orally administered, inexpensive, multivalent, temperature-stable, safe, and effective vaccine for children that could be particularly useful in developing nations, where multiple injections are not easily administered. Oral administration of vaccines should also reduce children's fear of shots at the doctor's office.

Alberta Provincial Pediatric EnTeric Infection TEam (APPETITE): epidemiology, emerging organisms, and economics.

PubMed

Freedman, Stephen B; Lee, Bonita E; Louie, Marie; Pang, Xiao-Li; Ali, Samina; Chuck, Andy; Chui, Linda; Currie, Gillian R; Dickinson, James; Drews, Steven J; Eltorki, Mohamed; Graham, Tim; Jiang, Xi; Johnson, David W; Kellner, James; Lavoie, Martin; MacDonald, Judy; MacDonald, Shannon; Svenson, Lawrence W; Talbot, James; Tarr, Phillip; Tellier, Raymond; Vanderkooi, Otto G

2015-07-31

Each year in Canada there are 5 million episodes of acute gastroenteritis (AGE) with up to 70% attributed to an unidentified pathogen. Moreover, 90% of individuals with AGE do not seek care when ill, thus, burden of disease estimates are limited by under-diagnosing and under-reporting. Further, little is known about the pathogens causing AGE as the majority of episodes are attributed to an "unidentified" etiology. Our team has two main objectives: 1) to improve health through enhanced enteric pathogen identification; 2) to develop economic models incorporating pathogen burden and societal preferences to inform enteric vaccine decision making. This project involves multiple stages: 1) Molecular microbiology experts will participate in a modified Delphi process designed to define criteria to aid in interpreting positive molecular enteric pathogen test results. 2) Clinical data and specimens will be collected from children aged 0-18 years, with vomiting and/or diarrhea who seek medical care in emergency departments, primary care clinics and from those who contact a provincial medical advice line but who do not seek care. Samples to be collected will include stool, rectal swabs (N = 2), and an oral swab. Specimens will be tested employing 1) stool culture; 2) in-house multiplex (N = 5) viral polymerase chain reaction (PCR) panel; and 3) multi-target (N = 15) PCR commercially available array. All participants will have follow-up data collected 14 days later to enable calculation of a Modified Vesikari Scale score and a Burden of Disease Index. Specimens will also be collected from asymptomatic children during their well child vaccination visits to a provincial public health clinic. Following the completion of the initial phases, discrete choice experiments will be conducted to enable a better understanding of societal preferences for diagnostic testing and vaccine policy. All of the results obtained will be integrated into economic models. This study is collecting novel

An assessment of enterotoxigenic Escherichia coli and Shigella vaccine candidates for infants and children.

PubMed

Walker, Richard I

2015-02-18

Despite improvements to water quality, sanitation, and the implementation of current prevention and treatment interventions, diarrhea remains a major cause of illness and death, especially among children less than five years of age in the developing world. Rotavirus vaccines have already begun making a real impact on diarrhea, but several more enteric vaccines will be necessary to achieve broader reductions of illness and death. Among the many causes of diarrheal disease, enterotoxigenic Escherichia coli (ETEC) and Shigella are the two most important bacterial pathogens for which there are no currently licensed vaccines. Vaccines against these two pathogens could greatly reduce the impact of disease caused by these infections. This review describes the approaches to ETEC and Shigella vaccines that are currently under development, including a range of both cellular and subunit approaches for each pathogen. In addition, the review discusses strategies for maximizing the potential benefit of these vaccines, which includes the feasibility of co-administration, consolidation, and combination of vaccine candidates, as well as issues related to effective administration of enteric vaccines to infants. Recent impact studies indicate that ETEC and Shigella vaccines could significantly benefit global public health. Either vaccine, particularly if they could be combined together or with another enteric vaccine, would be an extremely valuable tool for saving lives and promoting the health of infants and children in the developing world, as well as potentially providing protection to travelers and military personnel visiting endemic areas. Copyright © 2014 Elsevier Ltd. All rights reserved.

Frequency and predictors of seasonal influenza vaccination and reasons for refusal among patients at a large tertiary referral hospital.

PubMed

Masnick, Max; Leekha, Surbhi

2015-07-01

We assessed frequency and predictors of seasonal influenza vaccination acceptance among inpatients at a large tertiary referral hospital, as well as reasons for vaccination refusal. Over 5 seasons, >60% of patients unvaccinated on admission refused influenza vaccination while hospitalized; "believes not at risk" was the reason most commonly given.

Large-scale neuromorphic computing systems

NASA Astrophysics Data System (ADS)

Furber, Steve

2016-10-01

Neuromorphic computing covers a diverse range of approaches to information processing all of which demonstrate some degree of neurobiological inspiration that differentiates them from mainstream conventional computing systems. The philosophy behind neuromorphic computing has its origins in the seminal work carried out by Carver Mead at Caltech in the late 1980s. This early work influenced others to carry developments forward, and advances in VLSI technology supported steady growth in the scale and capability of neuromorphic devices. Recently, a number of large-scale neuromorphic projects have emerged, taking the approach to unprecedented scales and capabilities. These large-scale projects are associated with major new funding initiatives for brain-related research, creating a sense that the time and circumstances are right for progress in our understanding of information processing in the brain. In this review we present a brief history of neuromorphic engineering then focus on some of the principal current large-scale projects, their main features, how their approaches are complementary and distinct, their advantages and drawbacks, and highlight the sorts of capabilities that each can deliver to neural modellers.

Vaccines for Conservation: Plague, Prairie Dogs & Black-Footed Ferrets as a Case Study.

PubMed

Salkeld, Daniel J

2017-09-01

The endangered black-footed ferret (Mustela nigripes) is affected by plague, caused by Yersinia pestis, both directly, as a cause of mortality, and indirectly, because of the impacts of plague on its prairie dog (Cynomys spp.) prey base. Recent developments in vaccines and vaccine delivery have raised the possibility of plague control in prairie dog populations, thereby protecting ferret populations. A large-scale experimental investigation across the western US shows that sylvatic plague vaccine delivered in oral baits can increase prairie dog survival. In northern Colorado, an examination of the efficacy of insecticides to control fleas and plague vaccine shows that timing and method of plague control is important, with different implications for long-term and large-scale management of Y. pestis delivery. In both cases, the studies show that ambitious field-work and cross-sectoral collaboration can provide potential solutions to difficult issues of wildlife management, conservation and disease ecology.

Duck virus enteritis (duck plague) - a comprehensive update.

PubMed

Dhama, Kuldeep; Kumar, Naveen; Saminathan, Mani; Tiwari, Ruchi; Karthik, Kumaragurubaran; Kumar, M Asok; Palanivelu, M; Shabbir, Muhammad Zubair; Malik, Yashpal Singh; Singh, Raj Kumar

2017-12-01

Duck virus enteritis (DVE), also called duck plague, is one of the major contagious and fatal diseases of ducks, geese and swan. It is caused by duck enteritis virus (DEV)/Anatid herpesvirus-1 of the genus Mardivirus, family Herpesviridae, and subfamily Alpha-herpesvirinae. Of note, DVE has worldwide distribution, wherein migratory waterfowl plays a crucial role in its transmission within and between continents. Furthermore, horizontal and/ or vertical transmission plays a significant role in disease spread through oral-fecal discharges. Either of sexes from varying age groups of ducks is vulnerable to DVE. The disease is characterized by sudden death, vascular damage and subsequent internal hemorrhage, lesions in lymphoid organs, digestive mucosal eruptions, severe diarrhea and degenerative lesions in parenchymatous organs. Huge economic losses are connected with acute nature of the disease, increased morbidity and mortality (5%-100%), condemnations of carcasses, decreased egg production and hatchability. Although clinical manifestations and histopathology can provide preliminary diagnosis, the confirmatory diagnosis involves virus isolation and detection using serological and molecular tests. For prophylaxis, both live-attenuated and killed vaccines are being used in broiler and breeder ducks above 2 weeks of age. Since DEV is capable of becoming latent as well as shed intermittently, recombinant subunit and DNA vaccines either alone or in combination (polyvalent) are being targeted for its benign prevention. This review describes DEV, epidemiology, transmission, the disease (DVE), pathogenesis, and advances in diagnosis, vaccination and antiviral agents/therapies along with appropriate prevention and control strategies.

Lessons learned in shaping vaccine markets in low-income countries: a review of the vaccine market segment supported by the GAVI Alliance.

PubMed

Gilchrist, Shawn A N; Nanni, Angeline

2013-12-01

The Global Alliance for Vaccines and Immunization (GAVI) anticipated that growing demand for new vaccines could sufficiently impact the vaccines market to allow low-income countries (LICs) to self-finance new vaccines. But the time required to lower vaccine prices was underestimated and the amount that prices would decline overestimated. To better understand how prices in the LIC vaccine market can be impacted, the vaccine market was retrospectively examined. GAVI archives and the published literature on the vaccine markets in LICs were reviewed for the purpose of identifying GAVI's early assumptions for the evolution of vaccine prices, and contrasting these retrospectively with actual outcomes. The prices in Phases I and II of GAVI-supported vaccines failed to decline to a desirable level within a projected 5-year timeframe. GAVI-eligible countries were unable to sustain newly introduced vaccines without prolonged donor support. Two key lessons can be applied to future vaccine market-shaping strategies: (1) accurate demand forecasting together with committed donor funding can increase supply to the LIC vaccines market, but even greater strides can be made to increase the certainty of purchase; and (2) the expected time to lower prices took much longer than 5 years; market competition is inherently linked to the development time for new vaccines--a minimum of 5-10 or more years. Other factors that can lower vaccine prices include: large-scale production or alternate financing mechanisms that can hasten vaccine price maturation. The impacts of competition on vaccine prices in the LIC new-vaccines market occurred after almost 10 years. The time for research and development, acquisition of technological know-how and to scale production must be accounted for to more accurately predict significant declines on vaccine prices. Alternate financing mechanisms and the use of purchase agreements should also be considered for lowering prices when planning new vaccine

Pilot scale production of highly efficacious and stable enterovirus 71 vaccine candidates.

PubMed

Chou, Ai-Hsiang; Liu, Chia-Chyi; Chang, Cheng-Peng; Guo, Meng-Shin; Hsieh, Shih-Yang; Yang, Wen-Hsueh; Chao, Hsin-Ju; Wu, Chien-Long; Huang, Ju-Lan; Lee, Min-Shi; Hu, Alan Yung-Chi; Lin, Sue-Chen; Huang, Yu-Yun; Hu, Mei-Hua; Chow, Yen-Hung; Chiang, Jen-Ron; Chang, Jui-Yuan; Chong, Pele

2012-01-01

Enterovirus 71 (EV71) has caused several epidemics of hand, foot and mouth diseases (HFMD) in Asia and now is being recognized as an important neurotropic virus. Effective medications and prophylactic vaccine against EV71 infection are urgently needed. Based on the success of inactivated poliovirus vaccine, a prototype chemically inactivated EV71 vaccine candidate has been developed and currently in human phase 1 clinical trial. In this report, we present the development of a serum-free cell-based EV71 vaccine. The optimization at each step of the manufacturing process was investigated, characterized and quantified. In the up-stream process development, different commercially available cell culture media either containing serum or serum-free was screened for cell growth and virus yield using the roller-bottle technology. VP-SFM serum-free medium was selected based on the Vero cell growth profile and EV71 virus production. After the up-stream processes (virus harvest, diafiltration and concentration), a combination of gel-filtration liquid chromatography and/or sucrose-gradient ultracentrifugation down-stream purification processes were investigated at a pilot scale of 40 liters each. Although the combination of chromatography and sucrose-gradient ultracentrifugation produced extremely pure EV71 infectious virus particles, the overall yield of vaccine was 7-10% as determined by a VP2-based quantitative ELISA. Using chromatography as the downstream purification, the virus yield was 30-43%. To retain the integrity of virus neutralization epitopes and the stability of the vaccine product, the best virus inactivation was found to be 0.025% formalin-treatment at 37 °C for 3 to 6 days. Furthermore, the formalin-inactivated virion vaccine candidate was found to be stable for >18 months at 4 °C and a microgram of viral proteins formulated with alum adjuvant could induce strong virus-neutralizing antibody responses in mice, rats, rabbits, and non-human primates. These

Prevalence of positive antibody test results for canine parvovirus (CPV) and canine distemper virus (CDV) and response to modified live vaccination against CPV and CDV in dogs entering animal shelters.

PubMed

Litster, Annette; Nichols, Jamieson; Volpe, Allison

2012-05-25

Canine parvovirus (CPV) and canine distemper virus (CDV) infections are relatively common in animal shelters and are important population management issues since the immune status of incoming dogs is usually unknown. This study aimed to determine the prevalence of positive antibody test results for CPV and CDV in incoming dogs aged ≥ 4 months and to measure antibody response over 2 weeks following vaccination with a modified live vaccine (MLV). Dogs aged 4-24 months entering an adoption-guarantee shelter (Shelter 1, n=51) and aged ≥ 4 months entering a limited admission shelter (Shelter 2; n=51) were enrolled. Dogs from Shelter 1 had been vaccinated with MLV at a municipal shelter 5 days before enrollment, whereas dogs from Shelter 2 had no known history of vaccination at enrollment. Sera were obtained on day 1, immediately prior to CPV/CDV MLV, and tested using an in-clinic ELISA kit to detect CPV/CDV antibodies. Dogs negative for CPV and/or CDV were retested at day 6-8 and those dogs still negative at day 6-8 were retested at day 13-15. Prior to CPV/CDV MLV on day 1, more dogs tested positive for CPV (Shelter 1 - 68.6%; Shelter 2 - 84.3%) than for CDV (Shelter 1 - 37.3%; Shelter 2 - 41.2%). On day 1, prior to MLV, all spayed/neutered animals tested CPV antibody-positive (n=17/102) and CPV antibody-positive dogs were older than serologically negative dogs (Shelter 1, P=0.0029; Shelter 2, P=0.0042). By day 13-15, almost all dogs were CPV antibody-positive (Shelter 1 - 97.9%; Shelter 2 - 100.0%) and CDV antibody-positive (Shelter 1 - 93.8%; Shelter 2 - 97.8%). MLV induces protective antibody titers against CPV/CDV in almost all dogs after 13-15 days. Copyright © 2011 Elsevier B.V. All rights reserved.

A duck enteritis virus-vectored bivalent live vaccine provides fast and complete protection against H5N1 avian influenza virus infection in ducks.

PubMed

Liu, Jinxiong; Chen, Pucheng; Jiang, Yongping; Wu, Li; Zeng, Xianying; Tian, Guobin; Ge, Jinying; Kawaoka, Yoshihiro; Bu, Zhigao; Chen, Hualan

2011-11-01

Ducks play an important role in the maintenance of highly pathogenic H5N1 avian influenza viruses (AIVs) in nature, and the successful control of AIVs in ducks has important implications for the eradication of the disease in poultry and its prevention in humans. The inactivated influenza vaccine is expensive, labor-intensive, and usually needs 2 to 3 weeks to induce protective immunity in ducks. Live attenuated duck enteritis virus (DEV; a herpesvirus) vaccine is used routinely to control lethal DEV infections in many duck-producing areas. Here, we first established a system to generate the DEV vaccine strain by using the transfection of overlapping fosmid DNAs. Using this system, we constructed two recombinant viruses, rDEV-ul41HA and rDEV-us78HA, in which the hemagglutinin (HA) gene of the H5N1 virus A/duck/Anhui/1/06 was inserted and stably maintained within the ul41 gene or between the us7 and us8 genes of the DEV genome. Duck studies indicated that rDEV-us78HA had protective efficacy similar to that of the live DEV vaccine against lethal DEV challenge; importantly, a single dose of 10(6) PFU of rDEV-us78HA induced complete protection against a lethal H5N1 virus challenge in as little as 3 days postvaccination. The protective efficacy against both lethal DEV and H5N1 challenge provided by rDEV-ul41HA inoculation in ducks was slightly weaker than that provided by rDEV-us78HA. These results demonstrate, for the first time, that recombinant DEV is suitable for use as a bivalent live attenuated vaccine, providing rapid protection against both DEV and H5N1 virus infection in ducks.

Characteristics of a large mumps outbreak: Clinical severity, complications and association with vaccination status of mumps outbreak cases.

PubMed

Zamir, C Stein; Schroeder, H; Shoob, H; Abramson, N; Zentner, G

2015-01-01

In recent years, large mumps outbreaks, involving mainly adolescents and young adults, have re-emerged in several countries. We investigated a large mumps outbreak, evaluated the association between mumps clinical severity (complications, hospitalization) and vaccination status (number of previous measles, mumps and rubella - MMR vaccine doses), and assessed vaccine effectiveness. The first mumps cases emerged in an ultra-orthodox boys' school in Jerusalem and were epidemiologically linked to the mumps outbreak in New York. Overall, 3130 mumps cases were notified in the Jerusalem district during September 2009-August 2011 (median age 13y, 64% males). Most cases were reported from community clinics. Patients with systemic symptoms and/or complications (419, 13.4%) were either hospitalized (n = 79) or treated in an emergency medical center (n = 340). The main complications included orchitis (3.8% males> age 12y) and meningoencephalitis (0.5%). The mumps virus genotype was G5. The distribution of previous MMR vaccine doses (n = 0,1,2) was: 24.8%, 28.3% and 46.9%, respectively. The number of previous vaccine doses was inversely associated with clinical severity. Adjusted values for MMR vaccine effectiveness against complications were estimated as 52.1% (95% CI -4 -78%) for one vaccine dose and 62.7% (95% CI 25.7-81.3%) for 2 doses. The outbreak was characterized by predominance of male students; the majority of whom had been previously vaccinated. The reported complication rate was relatively low. Vaccination status was associated with age and disease severity. The combination of limited mumps vaccine effectiveness and the specific school setting (dense learning and living conditions) probably contributed to the disease spread.

Characteristics of a large mumps outbreak: Clinical severity, complications and association with vaccination status of mumps outbreak cases

PubMed Central

Zamir, C Stein; Schroeder, H; Shoob, H; Abramson, N; Zentner, G

2015-01-01

In recent years, large mumps outbreaks, involving mainly adolescents and young adults, have re-emerged in several countries. We investigated a large mumps outbreak, evaluated the association between mumps clinical severity (complications, hospitalization) and vaccination status (number of previous measles, mumps and rubella - MMR vaccine doses), and assessed vaccine effectiveness. The first mumps cases emerged in an ultra-orthodox boys' school in Jerusalem and were epidemiologically linked to the mumps outbreak in New York. Overall, 3130 mumps cases were notified in the Jerusalem district during September 2009-August 2011 (median age 13y, 64% males). Most cases were reported from community clinics. Patients with systemic symptoms and/or complications (419, 13.4%) were either hospitalized (n = 79) or treated in an emergency medical center (n = 340). The main complications included orchitis (3.8% males> age 12y) and meningoencephalitis (0.5%). The mumps virus genotype was G5. The distribution of previous MMR vaccine doses (n = 0,1,2) was: 24.8%, 28.3% and 46.9%, respectively. The number of previous vaccine doses was inversely associated with clinical severity. Adjusted values for MMR vaccine effectiveness against complications were estimated as 52.1% (95% CI −4 −78%) for one vaccine dose and 62.7% (95% CI 25.7–81.3%) for 2 doses. The outbreak was characterized by predominance of male students; the majority of whom had been previously vaccinated. The reported complication rate was relatively low. Vaccination status was associated with age and disease severity. The combination of limited mumps vaccine effectiveness and the specific school setting (dense learning and living conditions) probably contributed to the disease spread. PMID:25874726

Large-Scale Outflows in Seyfert Galaxies

NASA Astrophysics Data System (ADS)

Colbert, E. J. M.; Baum, S. A.

1995-12-01

\\catcode`\\@=11 \\ialign{m @th#1hfil ##hfil \\crcr#2\\crcr\\sim\\crcr}}} \\catcode`\\@=12 Highly collimated outflows extend out to Mpc scales in many radio-loud active galaxies. In Seyfert galaxies, which are radio-quiet, the outflows extend out to kpc scales and do not appear to be as highly collimated. In order to study the nature of large-scale (>~1 kpc) outflows in Seyferts, we have conducted optical, radio and X-ray surveys of a distance-limited sample of 22 edge-on Seyfert galaxies. Results of the optical emission-line imaging and spectroscopic survey imply that large-scale outflows are present in >~{{1} /{4}} of all Seyferts. The radio (VLA) and X-ray (ROSAT) surveys show that large-scale radio and X-ray emission is present at about the same frequency. Kinetic luminosities of the outflows in Seyferts are comparable to those in starburst-driven superwinds. Large-scale radio sources in Seyferts appear diffuse, but do not resemble radio halos found in some edge-on starburst galaxies (e.g. M82). We discuss the feasibility of the outflows being powered by the active nucleus (e.g. a jet) or a circumnuclear starburst.

Impact of 2-, 4- and 9-valent HPV vaccines on morbidity and mortality from cervical cancer

PubMed Central

Luckett, Rebecca; Feldman, Sarah

2016-01-01

ABSTRACT Cervical cancer causes significant morbidity and mortality worldwide. Most cervical cancers are associated with oncogenic human papillomavirus (HPV), and vaccination with any of 3 available HPV vaccines is anticipated to greatly reduce the burden of cervical cancer. This review provides an overview of the burden of HPV, the efficacy and clinical effectiveness of the bivalent (HPV 16, 18), quadrivalent (HPV 6, 11, 16, 18) and 9vHPV (HPV 6, 11, 16, 1831, 33, 45, 52, 58) vaccines in order to assess the anticipated impact on cervical cancer. All three vaccines show high efficacy in prevention of vaccine-specific HPV-type infection and associated high-grade cervical dysplasia in HPV-naïve women. Early clinical effectiveness data for the bivalent and quadrivalent vaccine demonstrate reduced rates of HPV 16 and 18 prevalence in vaccinated cohorts; data evaluating cervical dysplasia and cervical procedures as outcomes will shed further light on the clinical effectiveness of both vaccines. The bivalent vaccine has demonstrated cross-protection to non-vaccine HPV types, including the types in the 9vHPV vaccine. No clinical effectiveness data is yet available for the 9vHPV vaccine.  While HPV vaccination has great promise to reduce cervical cancer morbidity and mortality, estimated benefits are largely theoretical at present. Large population-based clinical effectiveness studies will provide long-term immunogenicity and effectiveness, as well as assessment of cervical cancer as an endpoint, particularly as young vaccinated women enter the appropriate age range to initiate screening for cervical cancer. Strengthening screening and treatment programs will likely have the greatest impact in the short-term on cervical cancer morbidity and mortality PMID:26588179

A Large Size Chimeric Highly Immunogenic Peptide Presents Multistage Plasmodium Antigens as a Vaccine Candidate System against Malaria.

PubMed

Lozano, José Manuel; Varela, Yahson; Silva, Yolanda; Ardila, Karen; Forero, Martha; Guasca, Laura; Guerrero, Yuly; Bermudez, Adriana; Alba, Patricia; Vanegas, Magnolia; Patarroyo, Manuel Elkin

2017-11-01

Rational strategies for obtaining malaria vaccine candidates should include not only a proper selection of target antigens for antibody stimulation, but also a versatile molecular design based on ordering the right pieces from the complex pathogen molecular puzzle towards more active and functional immunogens. Classical Plasmodium falciparum antigens regarded as vaccine candidates have been selected as model targets in this study. Among all possibilities we have chosen epitopes of Pf CSP, STARP; MSA1 and Pf 155/RESA from pre- and erythrocyte stages respectively for designing a large 82-residue chimeric immunogen. A number of options aimed at diminishing steric hindrance for synthetic procedures were assessed based on standard Fmoc chemistry such as building block orthogonal ligation; pseudo-proline and microwave-assisted procedures, therefore the large-chimeric target was produced, characterized and immunologically tested. Antigenicity and functional in vivo efficacy tests of the large-chimera formulations administered alone or as antigen mixtures have proven the stimulation of high antibody titers, showing strong correlation with protection and parasite clearance of vaccinated BALB/c mice after being lethally challenged with both P. berghei -ANKA and P. yoelii 17XL malaria strains. Besides, 3D structure features shown by the large-chimera encouraged as to propose using these rational designed large synthetic molecules as reliable vaccine candidate-presenting systems.

Succeeding in New Vaccine Introduction: Lessons Learned From the Introduction of Inactivated Poliovirus Vaccine in Cameroon, Kenya, and Nigeria

PubMed Central

Snidal, Sarah; Saidu, Yauba; Ojumu, Abiola; Ngatia, Antony; Bagana, Murtala; Mutuku, Faith; Sobngwi, Joelle; Efe-Aluta, Oniovo; Roper, Julia; LeTallec, Yann; Kang’ethe, Alice

2017-01-01

Abstract Introducing a new vaccine is a large-scale endeavor that can face many challenges, resulting in introduction delays and inefficiencies. The development of national task teams and tools, such as prelaunch trackers, for the introduction of new vaccines (hereafter, “new vaccine introductions” [NVIs]) can help countries implement robust project management systems, front-load critical preparatory activities, and ensure continuous communication around vaccine supply and financing. In addition, implementing postlaunch assessments to take rapid corrective action accelerates the uptake of the new vaccines. NVIs can provide an opportunity to strengthen routine immunization, through strengthening program management systems or by reinforcing local immunization managers’ abilities, among others. This article highlights key lessons learned during the introduction of inactivated poliovirus vaccine in 3 countries that would make future NVIs more successful. The article concludes by considering how the Immunization Systems Management Group of the Global Polio Eradication Initiative has been useful to the NVI process and how such global structures could be further enhanced. PMID:28838156

Poverty reduction and equity benefits of introducing or scaling up measles, rotavirus and pneumococcal vaccines in low-income and middle-income countries: a modelling study.

PubMed

Riumallo-Herl, Carlos; Chang, Angela Y; Clark, Samantha; Constenla, Dagna; Clark, Andrew; Brenzel, Logan; Verguet, Stéphane

2018-01-01

Beyond their impact on health, vaccines can lead to large economic benefits. While most economic evaluations of vaccines have focused on the health impact of vaccines at a national scale, it is critical to understand how their impact is distributed along population subgroups. We build a financial risk protection model to evaluate the impact of immunisation against measles, severe pneumococcal disease and severe rotavirus for birth cohorts vaccinated over 2016-2030 for three scenarios in 41 Gavi-eligible countries: no immunisation, current immunisation coverage forecasts and the current immunisation coverage enhanced with funding support. We distribute modelled disease cases per socioeconomic group and derive the number of cases of: (1) catastrophic health costs (CHCs) and (2) medical impoverishment. In the absence of any vaccine coverage, the number of CHC cases attributable to measles, severe pneumococcal disease and severe rotavirus would be approximately 18.9 million, 6.6 million and 2.2 million, respectively. Expanding vaccine coverage would reduce this number by up to 90%, 30% and 40% in each case. More importantly, we find a higher share of CHC incidence among the poorest quintiles who consequently benefit more from vaccine expansion. Our findings contribute to the understanding of how vaccines can have a broad economic impact. In particular, we find that immunisation programmes can reduce the proportion of households facing catastrophic payments from out-of-pocket health expenses, mainly in lower socioeconomic groups. Thus, vaccines could have an important role in poverty reduction.

[Vaccination for international travelers].

PubMed

Arrazola, M Pilar; Serrano, Almudena; López-Vélez, Rogelio

2016-05-01

Traveler's vaccination is one of the key strategies for the prevention of infectious diseases during international travel. The risk of acquiring an infectious disease is determined in each case by the characteristics of the traveler and the travel, so the pre-departure medical advice of the traveler must be individualized. The World Health Organization classifies travelerś vaccines into three groups. - Vaccines for routine use in national immunization programs: Haemophilus influenzae type b, hepatitis B, polio, measles-mumps-rubella, tetanus-diphtheria-whooping a cough, and chickenpox. - Vaccinations required by law in certain countries before to enter them: yellow fever, meningococcal disease and poliomyelitis. - Vaccines recommended depending on the circumstances: cholera, japanese encephalitis, tick-borne encephalitis, meningococcal disease, typhoid fever, influenza, hepatitis A, hepatitis B, rabies and BCG. This review is intended to introduce the reader to the field of international vaccination. Copyright © 2016 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Synchronization of coupled large-scale Boolean networks

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

Li, Fangfei, E-mail: li-fangfei@163.com

2014-03-15

This paper investigates the complete synchronization and partial synchronization of two large-scale Boolean networks. First, the aggregation algorithm towards large-scale Boolean network is reviewed. Second, the aggregation algorithm is applied to study the complete synchronization and partial synchronization of large-scale Boolean networks. Finally, an illustrative example is presented to show the efficiency of the proposed results.

Booster Vaccination: The Role of Reduced Antigen Content Vaccines as a Preschool Booster

PubMed Central

Conversano, Michele; Zivelonghi, Giambattista; Zoppi, Giorgio

2014-01-01

The need for boosters for tetanus, diphtheria, pertussis, and polio, starting from preschool age, is related to the waning immune protection conferred by vaccination, the elimination/reduction of natural boosters due to large-scale immunization programs, and the possibility of reintroduction of wild agents from endemic areas. Taking into account the relevance of safety/tolerability in the compliance with vaccination among the population, it have been assessed whether today enough scientific evidences are available to support the use of dTap-IPV booster in preschool age. The review of the literature was conducted using the PubMed search engine. A total of 41 works has been selected; besides, the documentation produced by the World Health Organization, the European Centre for Disease Control, and the Italian Ministry of Health has been consulted. Many recent papers confirm the opportunity to use a low antigenic dose vaccine starting from 4 to 6 years of age. There is also evidence that 10 years after immunization the rate of seroprotected subjects against diphtheria does not differ significantly between those vaccinated with paediatric dose (DTaP) or reduced dose (dTaP or dTap) product. The dTpa vaccine is highly immunogenic for diphtheria toxoids regardless of prior vaccination history (2 + 1 and 3 + 1 schedules). PMID:24678509

Toxin-neutralizing antibodies protect against Clostridium perfringens-induced necrosis in an intestinal loop model for bovine necrohemorrhagic enteritis.

PubMed

Goossens, Evy; Verherstraeten, Stefanie; Valgaeren, Bonnie R; Pardon, Bart; Timbermont, Leen; Schauvliege, Stijn; Rodrigo-Mocholí, Diego; Haesebrouck, Freddy; Ducatelle, Richard; Deprez, Piet R; Van Immerseel, Filip

2016-06-13

Bovine necrohemorrhagic enteritis is caused by Clostridium perfringens type A. Due to the rapid progress and fatal outcome of the disease, vaccination would be of high value. In this study, C. perfringens toxins, either as native toxins or after formaldehyde inactivation, were evaluated as possible vaccine antigens. We determined whether antisera raised in calves against these toxins were able to protect against C. perfringens challenge in an intestinal loop model for bovine necrohemorrhagic enteritis. Alpha toxin and perfringolysin O were identified as the most immunogenic proteins in the vaccine preparations. All vaccines evoked a high antibody response against the causative toxins, alpha toxin and perfringolysin O, as detected by ELISA. All antibodies were able to inhibit the activity of alpha toxin and perfringolysin O in vitro. However, the antibodies raised against the native toxins were more inhibitory to the C. perfringens-induced cytotoxicity (as tested on bovine endothelial cells) and only these antibodies protected against C. perfringens challenge in the intestinal loop model. Although immunization of calves with both native and formaldehyde inactivated toxins resulted in high antibody titers against alpha toxin and perfringolysin O, only antibodies raised against native toxins protect against C. perfringens challenge in an intestinal loop model for bovine necrohemorrhagic enteritis.

Dissecting the large-scale galactic conformity

NASA Astrophysics Data System (ADS)

Seo, Seongu

2018-01-01

Galactic conformity is an observed phenomenon that galaxies located in the same region have similar properties such as star formation rate, color, gas fraction, and so on. The conformity was first observed among galaxies within in the same halos (“one-halo conformity”). The one-halo conformity can be readily explained by mutual interactions among galaxies within a halo. Recent observations however further witnessed a puzzling connection among galaxies with no direct interaction. In particular, galaxies located within a sphere of ~5 Mpc radius tend to show similarities, even though the galaxies do not share common halos with each other ("two-halo conformity" or “large-scale conformity”). Using a cosmological hydrodynamic simulation, Illustris, we investigate the physical origin of the two-halo conformity and put forward two scenarios. First, back-splash galaxies are likely responsible for the large-scale conformity. They have evolved into red galaxies due to ram-pressure stripping in a given galaxy cluster and happen to reside now within a ~5 Mpc sphere. Second, galaxies in strong tidal field induced by large-scale structure also seem to give rise to the large-scale conformity. The strong tides suppress star formation in the galaxies. We discuss the importance of the large-scale conformity in the context of galaxy evolution.

Recombinant protein vaccines produced in insect cells.

PubMed

Cox, Manon M J

2012-02-27

The baculovirus-insect cell expression system is a well known tool for the production of complex proteins. The technology is also used for commercial manufacture of various veterinary and human vaccines. This review paper provides an overview of how this technology can be applied to produce a multitude of vaccine candidates. The key advantage of this recombinant protein manufacturing platform is that a universal "plug and play" process may be used for producing a broad range of protein-based prophylactic and therapeutic vaccines for both human and veterinary use while offering the potential for low manufacturing costs. Large scale mammalian cell culture facilities previously established for the manufacturing of monoclonal antibodies that have now become obsolete due to yield improvement could be deployed for the manufacturing of these vaccines. Alternatively, manufacturing capacity could be established in geographic regions that do not have any vaccine production capability. Dependent on health care priorities, different vaccines could be manufactured while maintaining the ability to rapidly convert to producing pandemic influenza vaccine when the need arises. Copyright © 2012 Elsevier Ltd. All rights reserved.

Pharmacy management of vaccines.

PubMed

Cannon, H Eric

2007-09-01

Although standard vaccines have traditionally been granted full coverage in managed care, the recent introduction of several novel vaccine products has necessitated the revision of pharmacy management strategies throughout the nation. To review pharmacy management strategies for a number of emerging vaccines, with unique plan perspectives from SelectHealth, an Intermountain Healthcare company serving approximately 500,000 members in Utah. Because several recently introduced vaccines target previously unaddressed diseases and carry higher costs than traditional vaccines, several plans have adapted a novel approach to manage vaccine coverage on an individual product basis. At SelectHealth, recently introduced vaccines for rotavirus, respiratory syncytial virus (RSV), herpes zoster, and human papillomavirus (HPV) have required special attention in terms of pharmacy management. After carefully weighing acquisition and administration costs, anticipated uptake and use, direct and indirect health care costs averted, and quality of life issues, plan leadership decided to cover many of the new vaccines (i.e., rotavirus, RSV, and herpes zoster) under a nonstandard vaccination benefit. However, because substantial cost savings and high use of the quadrivalent HPV vaccine was anticipated within SelectHealth, the plan decided to fully cover the product. Although they complicate traditional pharmacy management, novel vaccines provide clinical benefit that managed care organizations cannot ignore. One universal strategy will not suffice in managing all the different vaccines entering the market, and a tailored approach should be employed based on the individual characteristics and use of each product.

The development and manufacture of influenza vaccines

PubMed Central

Buckland, Barry C

2015-01-01

The development and manufacture of an Influenza vaccine is unlike any other product in the Vaccine industry because of the need to change composition on a yearly basis. The poor efficacy of Influenza vaccines over the past 2 y in the Northern Hemisphere invites questions on how the vaccines are manufactured and how change in vaccine composition is controlled. The opinion expressed in this commentary is that the risk of not making the correct HA protein is increased by the need to adapt the new seasonal virus for good propagation in embryonated chicken eggs. This adaptation is required because not enough doses can be made in time for the new 'flu season unless productivity is reasonable. This problem is not necessarily solved by going to a cell culture host for virus propagation and that may explain why this more advanced technology approach is not more widely used. A vaccine based on hemagglutinin (HA) protein that does not involve Influenza virus propagation (such as Flublok®) side steps this particular problem. The exact HA sequence can be used as is in the virus. The technology can be run at large scale, already at 2 × 21,000L in Japan, in contrast to eggs where scale-up is by multiplication; the HA product is highly purified and made consistently in the form of rosettes. PMID:25844949

The Large -scale Distribution of Galaxies

NASA Astrophysics Data System (ADS)

Flin, Piotr

A review of the Large-scale structure of the Universe is given. A connection is made with the titanic work by Johannes Kepler in many areas of astronomy and cosmology. A special concern is made to spatial distribution of Galaxies, voids and walls (cellular structure of the Universe). Finaly, the author is concluding that the large scale structure of the Universe can be observed in much greater scale that it was thought twenty years ago.

Sex and Vaccination

ERIC Educational Resources Information Center

Zavrel, Erik; Herreid, Clyde Freeman

2008-01-01

This case study is centered upon the recent debate concerning the decision by Texas Governor Rick Perry to mandate the compulsory vaccination of girls in the Texas public school system against the human papillomavirus (HPV) prior to entering the sixth grade. The interrupted case method is particularly appropriate for this subject with the case…

Vaccines in Shelters and Group Settings.

PubMed

Squires, Richard A

2018-03-01

Dogs and cats entering animal shelters are at high risk of acquiring 1 or more contagious infectious diseases. Such animals may be severely stressed, exhausted, and unwell, as well as malnourished and parasitized. The typically high throughput of shelter animals, many of them young and of unknown vaccination status, plays a role. Vaccines are a crucially important part of the management approach to limiting morbidity, mortality, and spread of infection. Guidelines for the use of vaccines in shelters have been published and are reviewed and discussed in this article. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

The expected emotional benefits of influenza vaccination strongly affect pre-season intentions and subsequent vaccination among healthcare personnel.

PubMed

Thompson, Mark G; Gaglani, Manjusha J; Naleway, Allison; Ball, Sarah; Henkle, Emily M; Sokolow, Leslie Z; Brennan, Beth; Zhou, Hong; Foster, Lydia; Black, Carla; Kennedy, Erin D; Bozeman, Sam; Grohskopf, Lisa A; Shay, David K

2012-05-21

The relative importance of different attitudes in predicting vaccination among healthcare personnel (HCP) is unclear. We hypothesized that HCP who feel at risk without vaccination or say they would regret not getting vaccinated would be more likely to get vaccinated than HCP who do not expect these emotional benefits. A prospective cohort of 1544 HCP with direct patient care was enrolled from September 18 to December 18, 2010 at Scott & White Healthcare in Texas and Kaiser Permanente Northwest in Oregon and Washington. An Internet-based questionnaire assessed pre-season intention to be vaccinated and included 12 questions on attitudes about vaccination: single-item measures of perceived susceptibility and vaccine effectiveness, 5 items that were summed to form a concerns about vaccine scale, and 5 items summed to form an emotional benefits of vaccination scale. Influenza vaccination status for the 2010-2011 season and for 5 prior seasons was confirmed by medical record extraction. There were significant differences between vaccinated and unvaccinated HCP on all attitude items; 72% of vaccinated HCP agreed that they "worry less about getting the flu" if vaccinated, compared to only 26% of the unvaccinated (odds ratio=7.4, 95% confidence interval=5.8-9.5). In a multivariate model, the emotional benefits scale was the strongest predictor of 2010-2011 seasonal influenza vaccination, after adjusting for other attitude measures, prior vaccination history, and pre-season intention to be vaccinated. The predictive value of the emotional benefits scale was strongest for HCP with low pre-season intention to be vaccinated, where HCP vaccine receipt was 15% versus 83% for those with low versus high scores on the emotional benefits scale. The expected emotional benefits of vaccination strongly affect seasonal influenza vaccination among HCP, even after taking into account other attitudes, pre-season intentions, and prior vaccination history. These attitudes are promising

Large scale dynamic systems

NASA Technical Reports Server (NTRS)

Doolin, B. F.

1975-01-01

Classes of large scale dynamic systems were discussed in the context of modern control theory. Specific examples discussed were in the technical fields of aeronautics, water resources and electric power.

[Vaccinations in psychiatry].

PubMed

Dols, A; van den Brink, W; Eikelenboom, P

2009-01-01

Vaccination is a well-known strategy for preventing and treating infections. The purpose of vaccinations is to render antigens harmless by the production of antibodies. In psychiatry there are also situations where antigens that have been introduced from outside or that have developed during an illness constitute a threat to the patient's health. To explore the possible applications of vaccination in psychiatry. In this article we discuss the applications of vaccination in psychiatry on the basis of two examples. In addiction research, trials are being conducted with antibodies against substances such as cocaine and nicotine in order to prevent such addictive substances from crossing the blood-brain barrier and thereby initiating their rewarding effect. The first clinical results are very promising, but vaccines have not yet been applied clinically. With regard to Alzheimer's disease it has been shown by means of animal models that specific antibodies can prevent AlphaBeta aggregation and dissolve existing aggregates. On the basis of these findings various large-scale clinical trials have begun in order to study immunotherapy for Alzheimer's disease. The first clinical results showed little neurocognitive effects. A wellknown study had to be terminated because of side-effects of the therapy, in the form of neuro-encephalitis. Our tentative conclusion is that the clinical application of immunotherapy in psychiatry still has its limitations, but is indeed promising.

mRNA Cancer Vaccines-Messages that Prevail.

PubMed

Grunwitz, Christian; Kranz, Lena M

2017-01-01

During the last decade, mRNA became increasingly recognized as a versatile tool for the development of new innovative therapeutics. Especially for vaccine development, mRNA is of outstanding interest and numerous clinical trials have been initiated. Strikingly, all of these studies have proven that large-scale GMP production of mRNA is feasible and concordantly report a favorable safety profile of mRNA vaccines. Induction of T-cell immunity is a multi-faceted process comprising antigen acquisition, antigen processing and presentation, as well as immune stimulation. The effectiveness of mRNA vaccines is critically dependent on making the antigen(s) of interest available to professional antigen-presenting cells, especially DCs. Efficient delivery of mRNA into DCs in vivo remains a major challenge in the mRNA vaccine field. This review summarizes the principles of mRNA vaccines and highlights the importance of in vivo mRNA delivery and recent advances in harnessing their therapeutic potential.

Efficacy testing of a 35 year old commercially produced Yersinia ruckeri bacterin for the control of Enteric Redmouth ERM) Disease

USDA-ARS?s Scientific Manuscript database

In 1976 the United States Department of Agriculture, Veterinary Services, granted the first veterinary product license for a biologic to be administered to fish. That license was issued for Enteric Redmouth Bacterin (Yerisina ruckeri) to the first commercial fish vaccine company, Wildlife Vaccines. ...

Human papillomavirus vaccines and vaccine implementation.

PubMed

de Sanjosé, Silvia; Alemany, Laia; Castellsagué, Xavier; Bosch, F Xavier

2008-11-01

Countries are now challenged by the rapid development of vaccines aimed at the primary prevention of infections. In the years to come, several vaccines will need to be considered as potential candidates in routine immunization programs. Recently, two new vaccines against two/four types of human papillomavirus (HPV) have been commercialized. Bivalent HPV 16 and 18 (Cervarix) and quadrivalent HPV 6, 11, 16 and 18 (Gardasil) vaccines are now extensively used in some countries. These vaccines will prevent infection and long-running complications, such as cervical cancer, other HPV-related cancers and genital warts (for the quadrivalent vaccine). The beneficial effect of these vaccines will be largely observed in women. This article summarizes the burden of HPV preventable disease worldwide and briefly describes the impact of secondary prevention and the most relevant aspects of the current available vaccines, their efficacy and safety. Finally, some major aspects that are likely to impact the introduction of these vaccines around the world are outlined, with particular emphasis on developing countries.

Transition from large-scale to small-scale dynamo.

PubMed

Ponty, Y; Plunian, F

2011-04-15

The dynamo equations are solved numerically with a helical forcing corresponding to the Roberts flow. In the fully turbulent regime the flow behaves as a Roberts flow on long time scales, plus turbulent fluctuations at short time scales. The dynamo onset is controlled by the long time scales of the flow, in agreement with the former Karlsruhe experimental results. The dynamo mechanism is governed by a generalized α effect, which includes both the usual α effect and turbulent diffusion, plus all higher order effects. Beyond the onset we find that this generalized α effect scales as O(Rm(-1)), suggesting the takeover of small-scale dynamo action. This is confirmed by simulations in which dynamo occurs even if the large-scale field is artificially suppressed.

An evaluation of the emerging vaccines against influenza in children

PubMed Central

2013-01-01

influenza-associated disease rather than specifically influenza-associated pneumonia. Conclusion Although the landscape of emerging influenza vaccines shows several promising candidates, it is unlikely that the advancements in the newer vaccine technologies will be able to progress through to large scale production in the near future. The combined effects of continued investments in researching new vaccines and improvements of available vaccines will hopefully shorten the time needed to the development of an effective seasonal and pandemic influenza vaccine suitable for large scale production. PMID:24564565

An evaluation of the emerging vaccines against influenza in children.

PubMed

Nair, Harish; Lau, Eva; Brooks, W; Seong, Ang; Theodoratou, Evropi; Zgaga, Lina; Huda, Tanvir; Jadhav, Suresh S; Rudan, Igor; Campbell, Harry

2013-01-01

rather than specifically influenza-associated pneumonia. Although the landscape of emerging influenza vaccines shows several promising candidates, it is unlikely that the advancements in the newer vaccine technologies will be able to progress through to large scale production in the near future. The combined effects of continued investments in researching new vaccines and improvements of available vaccines will hopefully shorten the time needed to the development of an effective seasonal and pandemic influenza vaccine suitable for large scale production.

Perspectives of Immunization Program Managers on 2009-10 H1N1 Vaccination in the United States: A National Survey

PubMed Central

Seib, Katherine; Wells, Katelyn; Hannan, Claire; Orenstein, Walter A.; Whitney, Ellen A. S.; Hinman, Alan R.; Berkelman, Ruth L.; Omer, Saad B.

2012-01-01

Abstract In June and July 2010, we conducted a national internet-based survey of 64 city, state, and territorial immunization program managers (IPMs) to assess their experiences in managing the 2009-10 H1N1 influenza vaccination campaign. Fifty-four (84%) of the managers or individuals responsible for an immunization program responded to the survey. To manage the campaign, 76% indicated their health department activated an incident command system (ICS) and 49% used an emergency operations center (EOC). Forty percent indicated they shared the leadership of the campaign with their state-level emergency preparedness program. The managers' perceptions of the helpfulness of the emergency preparedness staff was higher when they had collaborated with the emergency preparedness program on actual or simulated mass vaccination events within the previous 2 years. Fifty-seven percent found their pandemic influenza plan helpful, and those programs that mandated that vaccine providers enter data into their jurisdiction's immunization information system (IIS) were more likely than those who did not mandate data entry to rate their IIS as valuable for facilitating registration of nontraditional providers (42% vs. 25%, p<0.05) and tracking recalled influenza vaccine (50% vs. 38%, p<0.05). Results suggest that ICS and EOC structures, pandemic influenza plans, collaborations with emergency preparedness partners during nonemergencies, and expanded use of IIS can enhance immunization programs' ability to successfully manage a large-scale vaccination campaign. Maintaining the close working relationships developed between state-level immunization and emergency preparedness programs during the H1N1 influenza vaccination campaign will be especially important as states prepare for budget cuts in the coming years. PMID:22360580

Large-Scale Hybrid Motor Testing. Chapter 10

NASA Technical Reports Server (NTRS)

Story, George

2006-01-01

Hybrid rocket motors can be successfully demonstrated at a small scale virtually anywhere. There have been many suitcase sized portable test stands assembled for demonstration of hybrids. They show the safety of hybrid rockets to the audiences. These small show motors and small laboratory scale motors can give comparative burn rate data for development of different fuel/oxidizer combinations, however questions that are always asked when hybrids are mentioned for large scale applications are - how do they scale and has it been shown in a large motor? To answer those questions, large scale motor testing is required to verify the hybrid motor at its true size. The necessity to conduct large-scale hybrid rocket motor tests to validate the burn rate from the small motors to application size has been documented in several place^'^^.^. Comparison of small scale hybrid data to that of larger scale data indicates that the fuel burn rate goes down with increasing port size, even with the same oxidizer flux. This trend holds for conventional hybrid motors with forward oxidizer injection and HTPB based fuels. While the reason this is occurring would make a great paper or study or thesis, it is not thoroughly understood at this time. Potential causes include the fact that since hybrid combustion is boundary layer driven, the larger port sizes reduce the interaction (radiation, mixing and heat transfer) from the core region of the port. This chapter focuses on some of the large, prototype sized testing of hybrid motors. The largest motors tested have been AMROC s 250K-lbf thrust motor at Edwards Air Force Base and the Hybrid Propulsion Demonstration Program s 250K-lbf thrust motor at Stennis Space Center. Numerous smaller tests were performed to support the burn rate, stability and scaling concepts that went into the development of those large motors.

Why small-scale cannabis growers stay small: five mechanisms that prevent small-scale growers from going large scale.

PubMed

Hammersvik, Eirik; Sandberg, Sveinung; Pedersen, Willy

2012-11-01

Over the past 15-20 years, domestic cultivation of cannabis has been established in a number of European countries. New techniques have made such cultivation easier; however, the bulk of growers remain small-scale. In this study, we explore the factors that prevent small-scale growers from increasing their production. The study is based on 1 year of ethnographic fieldwork and qualitative interviews conducted with 45 Norwegian cannabis growers, 10 of whom were growing on a large-scale and 35 on a small-scale. The study identifies five mechanisms that prevent small-scale indoor growers from going large-scale. First, large-scale operations involve a number of people, large sums of money, a high work-load and a high risk of detection, and thus demand a higher level of organizational skills than for small growing operations. Second, financial assets are needed to start a large 'grow-site'. Housing rent, electricity, equipment and nutrients are expensive. Third, to be able to sell large quantities of cannabis, growers need access to an illegal distribution network and knowledge of how to act according to black market norms and structures. Fourth, large-scale operations require advanced horticultural skills to maximize yield and quality, which demands greater skills and knowledge than does small-scale cultivation. Fifth, small-scale growers are often embedded in the 'cannabis culture', which emphasizes anti-commercialism, anti-violence and ecological and community values. Hence, starting up large-scale production will imply having to renegotiate or abandon these values. Going from small- to large-scale cannabis production is a demanding task-ideologically, technically, economically and personally. The many obstacles that small-scale growers face and the lack of interest and motivation for going large-scale suggest that the risk of a 'slippery slope' from small-scale to large-scale growing is limited. Possible political implications of the findings are discussed. Copyright

Generation of Large-Scale Magnetic Fields by Small-Scale Dynamo in Shear Flows.

PubMed

Squire, J; Bhattacharjee, A

2015-10-23

We propose a new mechanism for a turbulent mean-field dynamo in which the magnetic fluctuations resulting from a small-scale dynamo drive the generation of large-scale magnetic fields. This is in stark contrast to the common idea that small-scale magnetic fields should be harmful to large-scale dynamo action. These dynamos occur in the presence of a large-scale velocity shear and do not require net helicity, resulting from off-diagonal components of the turbulent resistivity tensor as the magnetic analogue of the "shear-current" effect. Given the inevitable existence of nonhelical small-scale magnetic fields in turbulent plasmas, as well as the generic nature of velocity shear, the suggested mechanism may help explain the generation of large-scale magnetic fields across a wide range of astrophysical objects.

Self-amplifying mRNA vaccines.

PubMed

Brito, Luis A; Kommareddy, Sushma; Maione, Domenico; Uematsu, Yasushi; Giovani, Cinzia; Berlanda Scorza, Francesco; Otten, Gillis R; Yu, Dong; Mandl, Christian W; Mason, Peter W; Dormitzer, Philip R; Ulmer, Jeffrey B; Geall, Andrew J

2015-01-01

This chapter provides a brief introduction to nucleic acid-based vaccines and recent research in developing self-amplifying mRNA vaccines. These vaccines promise the flexibility of plasmid DNA vaccines with enhanced immunogenicity and safety. The key to realizing the full potential of these vaccines is efficient delivery of nucleic acid to the cytoplasm of a cell, where it can amplify and express the encoded antigenic protein. The hydrophilicity and strong net negative charge of RNA impedes cellular uptake. To overcome this limitation, electrostatic complexation with cationic lipids or polymers and physical delivery using electroporation or ballistic particles to improve cellular uptake has been evaluated. This chapter highlights the rapid progress made in using nonviral delivery systems for RNA-based vaccines. Initial preclinical testing of self-amplifying mRNA vaccines has shown nonviral delivery to be capable of producing potent and robust innate and adaptive immune responses in small animals and nonhuman primates. Historically, the prospect of developing mRNA vaccines was uncertain due to concerns of mRNA instability and the feasibility of large-scale manufacturing. Today, these issues are no longer perceived as barriers in the widespread implementation of the technology. Currently, nonamplifying mRNA vaccines are under investigation in human clinical trials and can be produced at a sufficient quantity and quality to meet regulatory requirements. If the encouraging preclinical data with self-amplifying mRNA vaccines are matched by equivalently positive immunogenicity, potency, and tolerability in human trials, this platform could establish nucleic acid vaccines as a versatile new tool for human immunization. Copyright © 2015 Elsevier Inc. All rights reserved.

Enteric Fever in Children in Western Sydney, Australia, 2003-2015.

PubMed

Khatami, Ameneh; Khan, Fouzia; Macartney, Kristine K

2017-12-01

Enteric fever is a vaccine-preventable disease with cases in Australia predominantly acquired overseas. The aim of this study was to define the burden of enteric fever in children presenting to a pediatric hospital in Western Sydney between 2003 and 2015. Cases between January 2003 and December 2013 were ascertained through medical records using International Classification of Disease-coded discharge diagnoses, cross-referenced with microbiology laboratory data for all isolates of Salmonella enterica serovar typhi and S. enterica serovar paratyphi. Prospective cases from January 2014 to April 2015 were additionally captured through records maintained by the infectious diseases team. Seventy-one cases of enteric fever were identified in 12.3 years with an average of 4 cases per year between 2003 and 2008 and 7 cases per year between 2009 and 2014. Two were visitors to Australia, 8 were recent migrants, and 59 were Australian residents returning from overseas travel. Two children had no history of overseas travel. Countries of travel predominantly included the Indian subcontinent (60/69) and Southeast Asia (7/69). Of 30 children with information available on pretravel medical consultation, 1 was offered and received typhoid vaccine. Ninety-four percent of children (67) required admission for 1-28 days (median: 5 days). Three children required readmission, with 1 case of presumed relapse. Ninety percent (64) were diagnosed by blood or stool culture with S. enterica serovar typhi the predominant organism (54/64). In Australia, hospitalizations for pediatric enteric fever appear to be increasing; predominantly occurring in Australian-resident children. Greater awareness and education are required for parents and clinicians regarding travel health risks and prevention strategies.

Pain in adolescent girls receiving human papillomavirus vaccine with concomitantly administered vaccines.

PubMed

Walter, Emmanuel B; Kemper, Alex R; Dolor, Rowena J; Dunne, Eileen F

2015-02-01

Using the Faces Pain Scale - Revised, we assessed injection site pain 10 minutes after vaccination in young females randomized to receive either quadrivalent human papillomavirus vaccine (HPV4) before or after concomitantly administered vaccines. Although pain was modestly more after HPV4 injection than after other vaccines, the pain intensity after HPV4 injection was significantly less in those who received HPV4 before receiving other concomitant vaccines.

A universal vaccine for serogroup B meningococcus

PubMed Central

Giuliani, Marzia M.; Adu-Bobie, Jeannette; Comanducci, Maurizio; Aricò, Beatrice; Savino, Silvana; Santini, Laura; Brunelli, Brunella; Bambini, Stefania; Biolchi, Alessia; Capecchi, Barbara; Cartocci, Elena; Ciucchi, Laura; Di Marcello, Federica; Ferlicca, Francesca; Galli, Barbara; Luzzi, Enrico; Masignani, Vega; Serruto, Davide; Veggi, Daniele; Contorni, Mario; Morandi, Maurizio; Bartalesi, Alessandro; Cinotti, Vanda; Mannucci, Donatella; Titta, Francesca; Ovidi, Elisa; Welsch, Jo Anne; Granoff, Dan; Rappuoli, Rino; Pizza, Mariagrazia

2006-01-01

Meningitis and sepsis caused by serogroup B meningococcus are two severe diseases that still cause significant mortality. To date there is no universal vaccine that prevents these diseases. In this work, five antigens discovered by reverse vaccinology were expressed in a form suitable for large-scale manufacturing and formulated with adjuvants suitable for human use. The vaccine adjuvanted by aluminum hydroxide induced bactericidal antibodies in mice against 78% of a panel of 85 meningococcal strains representative of the global population diversity. The strain coverage could be increased to 90% and above by the addition of CpG oligonucleotides or by using MF59 as adjuvant. The vaccine has the potential to conquer one of the most devastating diseases of childhood. PMID:16825336

A universal vaccine for serogroup B meningococcus.

PubMed

Giuliani, Marzia M; Adu-Bobie, Jeannette; Comanducci, Maurizio; Aricò, Beatrice; Savino, Silvana; Santini, Laura; Brunelli, Brunella; Bambini, Stefania; Biolchi, Alessia; Capecchi, Barbara; Cartocci, Elena; Ciucchi, Laura; Di Marcello, Federica; Ferlicca, Francesca; Galli, Barbara; Luzzi, Enrico; Masignani, Vega; Serruto, Davide; Veggi, Daniele; Contorni, Mario; Morandi, Maurizio; Bartalesi, Alessandro; Cinotti, Vanda; Mannucci, Donatella; Titta, Francesca; Ovidi, Elisa; Welsch, Jo Anne; Granoff, Dan; Rappuoli, Rino; Pizza, Mariagrazia

2006-07-18

Meningitis and sepsis caused by serogroup B meningococcus are two severe diseases that still cause significant mortality. To date there is no universal vaccine that prevents these diseases. In this work, five antigens discovered by reverse vaccinology were expressed in a form suitable for large-scale manufacturing and formulated with adjuvants suitable for human use. The vaccine adjuvanted by aluminum hydroxide induced bactericidal antibodies in mice against 78% of a panel of 85 meningococcal strains representative of the global population diversity. The strain coverage could be increased to 90% and above by the addition of CpG oligonucleotides or by using MF59 as adjuvant. The vaccine has the potential to conquer one of the most devastating diseases of childhood.

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

Enteritis with pneumatosis intestinalis following rotavirus immunisation in an infant with short bowel syndrome.

PubMed

Lopez, Robert N; Krishnan, Usha; Ooi, Chee Y

2017-04-26

Rotavirus vaccines now form part of the national immunisation schedule in many countries. Contraindications to its use are few but do not currently include infants with short bowel syndrome (SBS). We present a nearly 3-month-old boy with SBS who developed enteritis with pneumatosis intestinalis following administration of the Rotarix vaccine. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Clostridium perfringens, necrotic enteritis and its vaccination in broiler chickens

USDA-ARS?s Scientific Manuscript database

Clostridium perfringens type A strains are the main etiological factors for necrotic enteritis (NE), one of the economically important gastrointestinal diseases in poultry responsible for the annual loss of 2 billion dollars in US poultry industry. NE has gained worldwide importance during the last...

Large Scale Traffic Simulations

DOT National Transportation Integrated Search

1997-01-01

Large scale microscopic (i.e. vehicle-based) traffic simulations pose high demands on computation speed in at least two application areas: (i) real-time traffic forecasting, and (ii) long-term planning applications (where repeated "looping" between t...

Quantitative Microbial Risk Assessment and Infectious Disease Transmission Modeling of Waterborne Enteric Pathogens.

PubMed

Brouwer, Andrew F; Masters, Nina B; Eisenberg, Joseph N S

2018-04-20

Waterborne enteric pathogens remain a global health threat. Increasingly, quantitative microbial risk assessment (QMRA) and infectious disease transmission modeling (IDTM) are used to assess waterborne pathogen risks and evaluate mitigation. These modeling efforts, however, have largely been conducted independently for different purposes and in different settings. In this review, we examine the settings where each modeling strategy is employed. QMRA research has focused on food contamination and recreational water in high-income countries (HICs) and drinking water and wastewater in low- and middle-income countries (LMICs). IDTM research has focused on large outbreaks (predominately LMICs) and vaccine-preventable diseases (LMICs and HICs). Human ecology determines the niches that pathogens exploit, leading researchers to focus on different risk assessment research strategies in different settings. To enhance risk modeling, QMRA and IDTM approaches should be integrated to include dynamics of pathogens in the environment and pathogen transmission through populations.

Induction of protective immunity against Eimeria tenella, Eimeria necatrix, Eimeria maxima and Eimeria acervulina infections using multivalent epitope DNA vaccines.

PubMed

Song, Xiaokai; Ren, Zhe; Yan, Ruofeng; Xu, Lixin; Li, Xiangrui

2015-06-04

Avian coccidiosis is mostly caused by mixed infection of several Eimeria species under natural conditions and immunity to avian coccidiosis is largely dependent on T-cell immune response. In this study, 14 T-cell epitope fragments from eight antigens of Eimeria tenella (E. tenella), Eimeria necatrix (E. necatrix), Eimeria maxima (E. maxima) and Eimeria acervulina (E. acervulina) were ligated with pVAX1 producing 14 monovalent DNA vaccines, respectively. Protective immunity of the monovalent DNA vaccines was assessed by in vivo challenge experiments and then four most protective fragments of each species were chosen to construct multivalent epitope DNA vaccines with or without chicken IL-2 as genetic adjuvant. Protective efficacies of the epitope DNA vaccines on chickens against E. tenella, E. necatrix, E. maxima and E. acervulina were evaluated. The results showed that the constructed multivalent epitope DNA vaccines significantly increased body weight gain, alleviated enteric lesions and reduced oocyst output of the infected birds. Especially, the multivalent epitope DNA vaccines of pVAX1-NA4-1-TA4-1-LDH-2-EMCDPK-1 and pVAX1-NA4-1-TA4-1-LDH-2-EMCDPK-1-IL-2 not only significantly increased body weight gain, alleviated enteric lesions and reduced oocyst output of the infected birds, but also resulted in anti-coccidial index (ACI) more than 170 against E. tenella, E. necatrix, E. maxima and E. acervulina, which indicated they could induce protective immunity against E. tenella, E. necatrix, E. maxima and E. acervulina. Our findings suggest the constructed multivalent epitope DNA vaccines are the potential candidate multivalent vaccines against mixed infection of Eimeria. Copyright © 2015 Elsevier Ltd. All rights reserved.

Generation of large-scale magnetic fields by small-scale dynamo in shear flows

DOE PAGES

Squire, J.; Bhattacharjee, A.

2015-10-20

We propose a new mechanism for a turbulent mean-field dynamo in which the magnetic fluctuations resulting from a small-scale dynamo drive the generation of large-scale magnetic fields. This is in stark contrast to the common idea that small-scale magnetic fields should be harmful to large-scale dynamo action. These dynamos occur in the presence of a large-scale velocity shear and do not require net helicity, resulting from off-diagonal components of the turbulent resistivity tensor as the magnetic analogue of the "shear-current" effect. Furthermore, given the inevitable existence of nonhelical small-scale magnetic fields in turbulent plasmas, as well as the generic naturemore » of velocity shear, the suggested mechanism may help explain the generation of large-scale magnetic fields across a wide range of astrophysical objects.« less

Vaccination against typhoid fever: present status.

PubMed Central

Ivanoff, B.; Levine, M. M.; Lambert, P. H.

1994-01-01

Typhoid fever remains an underestimated important health problem in many developing countries, causing more than 600,000 deaths annually in the world. Because of the reactogenicity of the parenteral, killed whole-cell vaccine, research has been oriented towards vaccination orally using live organisms and purified antigen. Live vaccine Ty21a, given by the oral route, has been extensively tested in several studies in developing countries. Its liquid formulation was the most effective, providing more than 60% protection after 7 years of follow-up. A Vi polysaccharide vaccine has been elaborated and provided more than 65% protection; after 3 years of follow-up the Vi antibody level was still at a high level. These two vaccines are therefore candidates for use in public health control programmes. Before such use, however, they need further evaluation for safety and protective efficacy when administered to the EPI-targeted age groups. The question of whether typhoid fever vaccines interfere with the response to simultaneously administered measles vaccine must also be studied. New live vaccines, given by the oral route in one dose, have been constructed through genetic engineering. The first results are promising, but they must be improved before use in a large-scale study. These strains could be used as live vector to deliver foreign antigens to the intestinal mucosa. PMID:7867143

Toward Increasing Fairness in Score Scale Calibrations Employed in International Large-Scale Assessments

ERIC Educational Resources Information Center

Oliveri, Maria Elena; von Davier, Matthias

2014-01-01

In this article, we investigate the creation of comparable score scales across countries in international assessments. We examine potential improvements to current score scale calibration procedures used in international large-scale assessments. Our approach seeks to improve fairness in scoring international large-scale assessments, which often…

Construction of a recombinant duck enteritis virus (DEV) expressing hemagglutinin of H5N1 avian influenza virus based on an infectious clone of DEV vaccine strain and evaluation of its efficacy in ducks and chickens.

PubMed

Wang, Jichun; Ge, Aimin; Xu, Mengwei; Wang, Zhisheng; Qiao, Yongfeng; Gu, Yiqi; Liu, Chang; Liu, Yamei; Hou, Jibo

2015-08-13

Highly pathogenic avian influenza virus (AIV) subtype H5N1 remains a threat to poultry. Duck enteritis virus (DEV)-vectored vaccines expressing AIV H5N1 hemagglutinin (HA) may be viable AIV and DEV vaccine candidates. To facilitate the generation and further improvement of DEV-vectored HA(H5) vaccines, we first constructed an infectious clone of DEV Chinese vaccine strain C-KCE (DEV(C-KCE)). Then, we generated a DEV-vectored HA(H5) vaccine (DEV-H5(UL55)) based on the bacterial artificial chromosome (BAC) by inserting a synthesized HA(H5) expression cassette with a pMCMV IE promoter and a consensus HA sequence into the noncoding area between UL55 and LORF11. The immunogenicity and protective efficacy of the resulting recombinant vaccine against DEV and AIV H5N1 were evaluated in both ducks and chickens. The successful construction of DEV BAC and DEV-H5(UL55) was verified by restriction fragment length polymorphism analysis. Recovered virus from the BAC or mutants showed similar growth kinetics to their parental viruses. The robust expression of HA in chicken embryo fibroblasts infected with the DEV-vectored vaccine was confirmed by indirect immunofluorescence and western blotting analyses. A single dose of 10(6) TCID50 DEV-vectored vaccine provided 100 % protection against duck viral enteritis in ducks, and the hemagglutination inhibition (HI) antibody titer of AIV H5N1 with a peak of 8.2 log2 was detected in 3-week-old layer chickens. In contrast, only very weak HI titers were observed in ducks immunized with 10(7) TCID50 DEV-vectored vaccine. A mortality rate of 60 % (6/10) was observed in 1-week-old specific pathogen free chickens inoculated with 10(6) TCID50 DEV-vectored vaccine. We demonstrate the following in this study. (i) The constructed BAC is a whole genome clone of DEV(C-KCE). (ii) The insertion of an HA expression cassette sequence into the noncoding area between UL55 and LORF11 of DEV(C-KCE) affects neither the growth kinetics of the virus nor its

Very Large Scale Integration (VLSI).

ERIC Educational Resources Information Center

Yeaman, Andrew R. J.

Very Large Scale Integration (VLSI), the state-of-the-art production techniques for computer chips, promises such powerful, inexpensive computing that, in the future, people will be able to communicate with computer devices in natural language or even speech. However, before full-scale VLSI implementation can occur, certain salient factors must be…

Toward Novel Vaccines Against Tuberculosis: Current Hopes and Obstacles

PubMed Central

Thaiss, Christoph A.; Kaufmann, Stefan H.E.

2010-01-01

Approximately 2 million people die of tuberculosis (TB) each year. The current vaccine, Bacille Calmette-Guérin (BCG), albeit widely employed, does not protect against adult pulmonary disease, and new vaccines are urgently needed to reduce the incidence of TB worldwide. New insights into the cellular and molecular mechanisms that underlie the interactions between Mycobacterium tuberculosis and its host have been exploited to develop novel vaccine candidates that recently have entered clinical trials. This review provides a brief overview of different approaches toward a new vaccination strategy and summarizes major challenges for the next decade. PMID:21165340

Salmonella-based plague vaccines for bioterrorism.

PubMed

Calhoun, Leona Nicole; Kwon, Young-Min

2006-04-01

Yersinia pestis, the causative agent of plague, is an emerging threat as a means of bioterrorism. Accordingly, the Working Group on Civilian Biodefense, as well as the Centers for Disease Control and Prevention, has specified Y. pestis as a prime candidate for use in bioterrorism. As the threat of bioterrorism increases, so does the need for an effective vaccine against this potential agent. Experts agree that a stable, non-invasive vaccine would be necessary for the rapid large-scale immunization of a population following a bioterrorism attack. Thus far, live Salmonella-based oral vaccines show the most potential for this purpose. When delivered via a mucosal route, Salmonella-based plague vaccines show the ability to protect against the deadly pneumonic form of plague. Also, mass production, distribution, and administration are easier and less costly for attenuated Salmonella-based plague vaccines than for plague vaccines consisting of purified proteins. Most attenuated Salmonella-based plague vaccines have utilized a plasmid-based expression system to deliver plague antigen(s) to the mucosa. However, these systems are frequently associated with plasmid instability, an increased metabolic burden upon the vaccine strain, and highly undesirable antibiotic resistance genes. The future of Salmonella-based plague vaccines seems to lie in the use of chromosomally encoded plague antigens and the use of in vivo inducible promoters to drive their expression. This method of vaccine development has been proven to greatly increase the retention of foreign genes, and also eliminates the need for antibiotic resistance genes within Salmonella-based vaccines.

A Virtual Clinic Improves Pneumococcal Vaccination for Asplenic Veterans at High Risk for Pneumococcal Disease

PubMed Central

Jump, Robin L.; Banks, Richard; Wilson, Brigid; Montpetite, Michelle M.; Carter, Rebecca; Phillips, Susan; Perez, Federico

2015-01-01

We developed a “virtual clinic” to improve pneumococcal vaccination among asplenic adults. Using an electronic medical record, we identified patients, assessed their vaccination status, entered orders, and notified patients and providers. Within 180 days, 38 of 76 patients (50%) received a pneumococcal vaccination. A virtual clinic may optimize vaccinations among high-risk patients. PMID:26668815

Physicians', Nurses', and Medical Assistants' Perceptions of the Human Papillomavirus Vaccine in a Large Integrated Health Care System.

PubMed

Mills, Jordan; Van Winkle, Patrick; Shen, Macy; Hong, Christina; Hudson, Sharon

2016-01-01

Vaccination against the human papillomavirus (HPV) decreases risks of cancer and genital warts and the need for gynecologic procedures, yet nationwide vaccination rates are low. Previous surveys exploring this phenomenon have not included input from nurses and medical assistants, who play integral roles in HPV vaccine delivery. To understand perceptions of HPV vaccine delivery among physicians, nurses, and medical assistants in a large integrated health care system in Southern California. Online surveys were sent to 13 nurse administrators and 75 physicians. Physicians were instructed to forward the survey to nurses and medical assistants with whom they work. A total of 76 surveys were completed, consisting of 52 physicians, 16 clinical nurses and medical assistants, and 8 nurse administrators. Physicians' perceptions of vaccine safety or strength of recommendation did not differ by specialty department. Physicians reportedly perceived the HPV vaccine as safer than did clinical nurses and medical assistants (p < 0.001), who indicated they wanted more education on the safety and efficacy of the vaccine before being comfortable strongly recommending it. Respondents advised that all clinicians could improve in their roles as HPV vaccine advocates through patient counseling and providing informational literature and that workflow standardization was needed to minimize missed vaccination opportunities. Physicians reportedly perceive the HPV vaccine as safer compared with nurses and medical assistants. Both groups think that more education of nonphysician staff is needed. Having proper systems in place is also vital to improving vaccination compliance.

Physicians’, Nurses’, and Medical Assistants’ Perceptions of the Human Papillomavirus Vaccine in a Large Integrated Health Care System

PubMed Central

Mills, Jordan; Van Winkle, Patrick; Shen, Macy; Hong, Christina; Hudson, Sharon

2016-01-01

Context Vaccination against the human papillomavirus (HPV) decreases risks of cancer and genital warts and the need for gynecologic procedures, yet nationwide vaccination rates are low. Previous surveys exploring this phenomenon have not included input from nurses and medical assistants, who play integral roles in HPV vaccine delivery. Objective To understand perceptions of HPV vaccine delivery among physicians, nurses, and medical assistants in a large integrated health care system in Southern California. Design Online surveys were sent to 13 nurse administrators and 75 physicians. Physicians were instructed to forward the survey to nurses and medical assistants with whom they work. Results A total of 76 surveys were completed, consisting of 52 physicians, 16 clinical nurses and medical assistants, and 8 nurse administrators. Physicians’ perceptions of vaccine safety or strength of recommendation did not differ by specialty department. Physicians reportedly perceived the HPV vaccine as safer than did clinical nurses and medical assistants (p < 0.001), who indicated they wanted more education on the safety and efficacy of the vaccine before being comfortable strongly recommending it. Respondents advised that all clinicians could improve in their roles as HPV vaccine advocates through patient counseling and providing informational literature and that workflow standardization was needed to minimize missed vaccination opportunities. Conclusion Physicians reportedly perceive the HPV vaccine as safer compared with nurses and medical assistants. Both groups think that more education of nonphysician staff is needed. Having proper systems in place is also vital to improving vaccination compliance. PMID:27643974

Survey on large scale system control methods

NASA Technical Reports Server (NTRS)

Mercadal, Mathieu

1987-01-01

The problem inherent to large scale systems such as power network, communication network and economic or ecological systems were studied. The increase in size and flexibility of future spacecraft has put those dynamical systems into the category of large scale systems, and tools specific to the class of large systems are being sought to design control systems that can guarantee more stability and better performance. Among several survey papers, reference was found to a thorough investigation on decentralized control methods. Especially helpful was the classification made of the different existing approaches to deal with large scale systems. A very similar classification is used, even though the papers surveyed are somehow different from the ones reviewed in other papers. Special attention is brought to the applicability of the existing methods to controlling large mechanical systems like large space structures. Some recent developments are added to this survey.

Large-Scale 3D Printing: The Way Forward

NASA Astrophysics Data System (ADS)

Jassmi, Hamad Al; Najjar, Fady Al; Ismail Mourad, Abdel-Hamid

2018-03-01

Research on small-scale 3D printing has rapidly evolved, where numerous industrial products have been tested and successfully applied. Nonetheless, research on large-scale 3D printing, directed to large-scale applications such as construction and automotive manufacturing, yet demands a great a great deal of efforts. Large-scale 3D printing is considered an interdisciplinary topic and requires establishing a blended knowledge base from numerous research fields including structural engineering, materials science, mechatronics, software engineering, artificial intelligence and architectural engineering. This review article summarizes key topics of relevance to new research trends on large-scale 3D printing, particularly pertaining (1) technological solutions of additive construction (i.e. the 3D printers themselves), (2) materials science challenges, and (3) new design opportunities.

Novel method to construct large-scale design space in lubrication process utilizing Bayesian estimation based on a small-scale design-of-experiment and small sets of large-scale manufacturing data.

PubMed

Maeda, Jin; Suzuki, Tatsuya; Takayama, Kozo

2012-12-01

A large-scale design space was constructed using a Bayesian estimation method with a small-scale design of experiments (DoE) and small sets of large-scale manufacturing data without enforcing a large-scale DoE. The small-scale DoE was conducted using various Froude numbers (X(1)) and blending times (X(2)) in the lubricant blending process for theophylline tablets. The response surfaces, design space, and their reliability of the compression rate of the powder mixture (Y(1)), tablet hardness (Y(2)), and dissolution rate (Y(3)) on a small scale were calculated using multivariate spline interpolation, a bootstrap resampling technique, and self-organizing map clustering. The constant Froude number was applied as a scale-up rule. Three experiments under an optimal condition and two experiments under other conditions were performed on a large scale. The response surfaces on the small scale were corrected to those on a large scale by Bayesian estimation using the large-scale results. Large-scale experiments under three additional sets of conditions showed that the corrected design space was more reliable than that on the small scale, even if there was some discrepancy in the pharmaceutical quality between the manufacturing scales. This approach is useful for setting up a design space in pharmaceutical development when a DoE cannot be performed at a commercial large manufacturing scale.

Quantitative Analysis of Repertoire-Scale Immunoglobulin Properties in Vaccine-Induced B-Cell Responses

DTIC Science & Technology

2017-05-10

repertoire-wide properties. Finally, through 75 the use of appropriate statistical analyses, the repertoire profiles can be quantitatively compared and 76...cell response to eVLP and 503 quantitatively compare GC B-cell repertoires from immunization conditions. We partitioned the 504 resulting clonotype... Quantitative analysis of repertoire-scale immunoglobulin properties in vaccine-induced B-cell responses Ilja V. Khavrutskii1, Sidhartha Chaudhury*1

A Duck Enteritis Virus-Vectored Bivalent Live Vaccine Provides Fast and Complete Protection against H5N1 Avian Influenza Virus Infection in Ducks ▿ † §

PubMed Central

Liu, Jinxiong; Chen, Pucheng; Jiang, Yongping; Wu, Li; Zeng, Xianying; Tian, Guobin; Ge, Jinying; Kawaoka, Yoshihiro; Bu, Zhigao; Chen, Hualan

2011-01-01

Ducks play an important role in the maintenance of highly pathogenic H5N1 avian influenza viruses (AIVs) in nature, and the successful control of AIVs in ducks has important implications for the eradication of the disease in poultry and its prevention in humans. The inactivated influenza vaccine is expensive, labor-intensive, and usually needs 2 to 3 weeks to induce protective immunity in ducks. Live attenuated duck enteritis virus (DEV; a herpesvirus) vaccine is used routinely to control lethal DEV infections in many duck-producing areas. Here, we first established a system to generate the DEV vaccine strain by using the transfection of overlapping fosmid DNAs. Using this system, we constructed two recombinant viruses, rDEV-ul41HA and rDEV-us78HA, in which the hemagglutinin (HA) gene of the H5N1 virus A/duck/Anhui/1/06 was inserted and stably maintained within the ul41 gene or between the us7 and us8 genes of the DEV genome. Duck studies indicated that rDEV-us78HA had protective efficacy similar to that of the live DEV vaccine against lethal DEV challenge; importantly, a single dose of 106 PFU of rDEV-us78HA induced complete protection against a lethal H5N1 virus challenge in as little as 3 days postvaccination. The protective efficacy against both lethal DEV and H5N1 challenge provided by rDEV-ul41HA inoculation in ducks was slightly weaker than that provided by rDEV-us78HA. These results demonstrate, for the first time, that recombinant DEV is suitable for use as a bivalent live attenuated vaccine, providing rapid protection against both DEV and H5N1 virus infection in ducks. PMID:21865383

A large population-based association study between HLA and KIR genotypes and measles vaccine antibody responses.

PubMed

Ovsyannikova, Inna G; Schaid, Daniel J; Larrabee, Beth R; Haralambieva, Iana H; Kennedy, Richard B; Poland, Gregory A

2017-01-01

Human antibody response to measles vaccine is highly variable in the population. Host genes contribute to inter-individual antibody response variation. The killer cell immunoglobulin-like receptors (KIR) are recognized to interact with HLA molecules and possibly influence humoral immune response to viral antigens. To expand on and improve our previous work with HLA genes, and to explore the genetic contribution of KIR genes to the inter-individual variability in measles vaccine-induced antibody responses, we performed a large population-based study in 2,506 healthy immunized subjects (ages 11 to 41 years) to identify HLA and KIR associations with measles vaccine-induced neutralizing antibodies. After correcting for the large number of statistical tests of allele effects on measles-specific neutralizing antibody titers, no statistically significant associations were found for either HLA or KIR loci. However, suggestive associations worthy of follow-up in other cohorts include B*57:01, DQB1*06:02, and DRB1*15:05 alleles. Specifically, the B*57:01 allele (1,040 mIU/mL; p = 0.0002) was suggestive of an association with lower measles antibody titer. In contrast, the DQB1*06:02 (1,349 mIU/mL; p = 0.0004) and DRB1*15:05 (2,547 mIU/mL; p = 0.0004) alleles were suggestive of an association with higher measles antibodies. Notably, the associations with KIR genotypes were strongly nonsignificant, suggesting that KIR loci in terms of copy number and haplotypes are not likely to play a major role in antibody response to measles vaccination. These findings refine our knowledge of the role of HLA and KIR alleles in measles vaccine-induced immunity.

A relativistic signature in large-scale structure

NASA Astrophysics Data System (ADS)

Bartolo, Nicola; Bertacca, Daniele; Bruni, Marco; Koyama, Kazuya; Maartens, Roy; Matarrese, Sabino; Sasaki, Misao; Verde, Licia; Wands, David

2016-09-01

In General Relativity, the constraint equation relating metric and density perturbations is inherently nonlinear, leading to an effective non-Gaussianity in the dark matter density field on large scales-even if the primordial metric perturbation is Gaussian. Intrinsic non-Gaussianity in the large-scale dark matter overdensity in GR is real and physical. However, the variance smoothed on a local physical scale is not correlated with the large-scale curvature perturbation, so that there is no relativistic signature in the galaxy bias when using the simplest model of bias. It is an open question whether the observable mass proxies such as luminosity or weak lensing correspond directly to the physical mass in the simple halo bias model. If not, there may be observables that encode this relativistic signature.

Dengue vaccines: Are they safe for travelers?

PubMed

Halstead, Scott B; Aguiar, Maira

2016-01-01

The four dengue viruses (DENV) circulate among nearly one-half of the world's population in tropical and semitropical countries imposing a huge morbidity burden on travelers. Sanofipasteur has developed a tetravalent live-attenuated vaccine, Dengvaxia, recently approved by the World Health Organization and licensed in four dengue-endemic countries. An additional two dengue vaccines, developed by the National Institute of Allergy and Infectious Diseases (NIAID), USA and Takeda, are entering phase III testing. Dengvaxia is composed of four yellow fever 17D-DENV chimeras, the NIAID vaccine contains three mutagenized DENV and one DENV2/4 chimera while the Takeda vaccine contains an attenuated DENV 2 and three DENV 2-DENV chimeras. Which of these vaccines might be useful in protecting travelers against dengue infections and disease? Dengvaxia requires three doses administered over the course of one year but in addition has safety signals suggesting that susceptible individuals should not be vaccinated. The NIAID vaccine is promising as a travel vaccine as a single dose fully protected susceptible adults against live dengue 2 virus challenge. The protective efficacy and safety of the Takeda vaccine remain to be demonstrated. Copyright © 2016 Elsevier Ltd. All rights reserved.

Bovine adenovirus-3 as a vaccine delivery vehicle.

PubMed

Ayalew, Lisanework E; Kumar, Pankaj; Gaba, Amit; Makadiya, Niraj; Tikoo, Suresh K

2015-01-15

The use of vaccines is an effective and relatively inexpensive means of controlling infectious diseases, which cause heavy economic losses to the livestock industry through animal loss, decreased productivity, treatment expenses and decreased carcass quality. However, some vaccines produced by conventional means are imperfect in many respects including virulence, safety and efficacy. Moreover, there are no vaccines for some animal diseases. Although genetic engineering has provided new ways of producing effective vaccines, the cost of production for veterinary use is a critical criterion for selecting the method of production and delivery of vaccines. The cost effective production and intrinsic ability to enter cells has made adenovirus vectors a highly efficient tool for delivery of vaccine antigens. Moreover, adenoviruses induce both humoral and cellular immune responses to expressed vaccine antigens. Since nonhuman adenoviruses are species specific, the development of animal specific adenoviruses as vaccine delivery vectors is being evaluated. This review summarizes the work related to the development of bovine adenovirus-3 as a vaccine delivery vehicle in animals, particularly cattle. Copyright © 2014 Elsevier Ltd. All rights reserved.

Cost of vaccinating refugees overseas versus after arrival in the United States, 2005.

PubMed

2008-03-07

Since 2000, approximately 50,000 refugees have entered the United States each year from various regions of the world. Although persons with immigrant status are legally required to be vaccinated before entering the United States, this requirement does not extend to U.S.-bound persons with refugee status. After 1 year in the United States, refugees can apply for a change of status to that of legal permanent resident, at which time they are required to be fully vaccinated in accordance with recommendations of the Advisory Committee on Immunization Practices (ACIP). A potentially less costly alternative might be to vaccinate U.S.-bound refugees overseas routinely, before they depart from refugee camps. To compare the cost of vaccinating refugees overseas versus after their arrival in the United States, CDC analyzed 2005 data on the number of refugees, cost of vaccine, and cost of vaccine administration. This report summarizes the results of that analysis, which suggested that, in 2005, vaccinating 50,787 refugees overseas would have cost an estimated $7.7 million, less than one third of the estimated $26.0 million cost of vaccinating in the United States. Costs were calculated from the perspective of the U.S. health-care system. To achieve public health cost savings, routine overseas vaccination of U.S.-bound refugees should be considered.

Recombinant modified vaccinia virus Ankara-based malaria vaccines.

PubMed

Sebastian, Sarah; Gilbert, Sarah C

2016-01-01

A safe and effective malaria vaccine is a crucial part of the roadmap to malaria elimination/eradication by the year 2050. Viral-vectored vaccines based on adenoviruses and modified vaccinia virus Ankara (MVA) expressing malaria immunogens are currently being used in heterologous prime-boost regimes in clinical trials for induction of strong antigen-specific T-cell responses and high-titer antibodies. Recombinant MVA is a safe and well-tolerated attenuated vector that has consistently shown significant boosting potential. Advances have been made in large-scale MVA manufacture as high-yield producer cell lines and high-throughput purification processes have recently been developed. This review describes the use of MVA as malaria vaccine vector in both preclinical and clinical studies in the past 5 years.

Vaccination intervention on epidemic dynamics in networks

NASA Astrophysics Data System (ADS)

Peng, Xiao-Long; Xu, Xin-Jian; Fu, Xinchu; Zhou, Tao

2013-02-01

Vaccination is an important measure available for preventing or reducing the spread of infectious diseases. In this paper, an epidemic model including susceptible, infected, and imperfectly vaccinated compartments is studied on Watts-Strogatz small-world, Barabási-Albert scale-free, and random scale-free networks. The epidemic threshold and prevalence are analyzed. For small-world networks, the effective vaccination intervention is suggested and its influence on the threshold and prevalence is analyzed. For scale-free networks, the threshold is found to be strongly dependent both on the effective vaccination rate and on the connectivity distribution. Moreover, so long as vaccination is effective, it can linearly decrease the epidemic prevalence in small-world networks, whereas for scale-free networks it acts exponentially. These results can help in adopting pragmatic treatment upon diseases in structured populations.

Next-generation dengue vaccines: novel strategies currently under development.

PubMed

Durbin, Anna P; Whitehead, Stephen S

2011-10-01

Dengue has become the most important arboviral infection worldwide with more than 30 million cases of dengue fever estimated to occur each year. The need for a dengue vaccine is great and several live attenuated dengue candidate vaccines are proceeding through clinical evaluation. The need to induce a balanced immune response against all four DENV serotypes with a single vaccine has been a challenge for dengue vaccine developers. A live attenuated DENV chimeric vaccine produced by Sanofi Pasteur has recently entered Phase III evaluation in numerous dengue-endemic regions of the world. Viral interference between serotypes contained in live vaccines has required up to three doses of the vaccine be given over a 12-month period of time. For this reason, novel DENV candidate vaccines are being developed with the goal of achieving a protective immune response with an immunization schedule that can be given over the course of a few months. These next-generation candidates include DNA vaccines, recombinant adenovirus vectored vaccines, alphavirus replicons, and sub-unit protein vaccines. Several of these novel candidates will be discussed.

Sound production due to large-scale coherent structures

NASA Technical Reports Server (NTRS)

Gatski, T. B.

1979-01-01

The acoustic pressure fluctuations due to large-scale finite amplitude disturbances in a free turbulent shear flow are calculated. The flow is decomposed into three component scales; the mean motion, the large-scale wave-like disturbance, and the small-scale random turbulence. The effect of the large-scale structure on the flow is isolated by applying both a spatial and phase average on the governing differential equations and by initially taking the small-scale turbulence to be in energetic equilibrium with the mean flow. The subsequent temporal evolution of the flow is computed from global energetic rate equations for the different component scales. Lighthill's theory is then applied to the region with the flowfield as the source and an observer located outside the flowfield in a region of uniform velocity. Since the time history of all flow variables is known, a minimum of simplifying assumptions for the Lighthill stress tensor is required, including no far-field approximations. A phase average is used to isolate the pressure fluctuations due to the large-scale structure, and also to isolate the dynamic process responsible. Variation of mean square pressure with distance from the source is computed to determine the acoustic far-field location and decay rate, and, in addition, spectra at various acoustic field locations are computed and analyzed. Also included are the effects of varying the growth and decay of the large-scale disturbance on the sound produced.

Hydrometeorological variability on a large french catchment and its relation to large-scale circulation across temporal scales

NASA Astrophysics Data System (ADS)

Massei, Nicolas; Dieppois, Bastien; Fritier, Nicolas; Laignel, Benoit; Debret, Maxime; Lavers, David; Hannah, David

2015-04-01

In the present context of global changes, considerable efforts have been deployed by the hydrological scientific community to improve our understanding of the impacts of climate fluctuations on water resources. Both observational and modeling studies have been extensively employed to characterize hydrological changes and trends, assess the impact of climate variability or provide future scenarios of water resources. In the aim of a better understanding of hydrological changes, it is of crucial importance to determine how and to what extent trends and long-term oscillations detectable in hydrological variables are linked to global climate oscillations. In this work, we develop an approach associating large-scale/local-scale correlation, enmpirical statistical downscaling and wavelet multiresolution decomposition of monthly precipitation and streamflow over the Seine river watershed, and the North Atlantic sea level pressure (SLP) in order to gain additional insights on the atmospheric patterns associated with the regional hydrology. We hypothesized that: i) atmospheric patterns may change according to the different temporal wavelengths defining the variability of the signals; and ii) definition of those hydrological/circulation relationships for each temporal wavelength may improve the determination of large-scale predictors of local variations. The results showed that the large-scale/local-scale links were not necessarily constant according to time-scale (i.e. for the different frequencies characterizing the signals), resulting in changing spatial patterns across scales. This was then taken into account by developing an empirical statistical downscaling (ESD) modeling approach which integrated discrete wavelet multiresolution analysis for reconstructing local hydrometeorological processes (predictand : precipitation and streamflow on the Seine river catchment) based on a large-scale predictor (SLP over the Euro-Atlantic sector) on a monthly time-step. This approach

The Challenge of Large-Scale Literacy Improvement

ERIC Educational Resources Information Center

Levin, Ben

2010-01-01

This paper discusses the challenge of making large-scale improvements in literacy in schools across an entire education system. Despite growing interest and rhetoric, there are very few examples of sustained, large-scale change efforts around school-age literacy. The paper reviews 2 instances of such efforts, in England and Ontario. After…

Large-scale influences in near-wall turbulence.

PubMed

Hutchins, Nicholas; Marusic, Ivan

2007-03-15

Hot-wire data acquired in a high Reynolds number facility are used to illustrate the need for adequate scale separation when considering the coherent structure in wall-bounded turbulence. It is found that a large-scale motion in the log region becomes increasingly comparable in energy to the near-wall cycle as the Reynolds number increases. Through decomposition of fluctuating velocity signals, it is shown that this large-scale motion has a distinct modulating influence on the small-scale energy (akin to amplitude modulation). Reassessment of DNS data, in light of these results, shows similar trends, with the rate and intensity of production due to the near-wall cycle subject to a modulating influence from the largest-scale motions.

Generation of large-scale magnetic fields by small-scale dynamo in shear flows

NASA Astrophysics Data System (ADS)

Squire, Jonathan; Bhattacharjee, Amitava

2015-11-01

A new mechanism for turbulent mean-field dynamo is proposed, in which the magnetic fluctuations resulting from a small-scale dynamo drive the generation of large-scale magnetic fields. This is in stark contrast to the common idea that small-scale magnetic fields should be harmful to large-scale dynamo action. These dynamos occur in the presence of large-scale velocity shear and do not require net helicity, resulting from off-diagonal components of the turbulent resistivity tensor as the magnetic analogue of the ``shear-current'' effect. The dynamo is studied using a variety of computational and analytic techniques, both when the magnetic fluctuations arise self-consistently through the small-scale dynamo and in lower Reynolds number regimes. Given the inevitable existence of non-helical small-scale magnetic fields in turbulent plasmas, as well as the generic nature of velocity shear, the suggested mechanism may help to explain generation of large-scale magnetic fields across a wide range of astrophysical objects. This work was supported by a Procter Fellowship at Princeton University, and the US Department of Energy Grant DE-AC02-09-CH11466.

Placebo use in vaccine trials: Recommendations of a WHO expert panel

PubMed Central

Rid, Annette; Saxena, Abha; Baqui, Abdhullah H.; Bhan, Anant; Bines, Julie; Bouesseau, Marie-Charlotte; Caplan, Arthur; Colgrove, James; Dhai, Ames; Gomez-Diaz, Rita; Green, Shane K.; Kang, Gagandeep; Lagos, Rosanna; Loh, Patricia; London, Alex John; Mulholland, Kim; Neels, Pieter; Pitisuttithum, Punee; Sarr, Samba Cor; Selgelid, Michael; Sheehan, Mark; Smith, Peter G.

2014-01-01

Vaccines are among the most cost-effective interventions against infectious diseases. Many candidate vaccines targeting neglected diseases in low- and middle-income countries are now progressing to large-scale clinical testing. However, controversy surrounds the appropriate design of vaccine trials and, in particular, the use of unvaccinated controls (with or without placebo) when an efficacious vaccine already exists. This paper specifies four situations in which placebo use may be acceptable, provided that the study question cannot be answered in an active-controlled trial design; the risks of delaying or foregoing an efficacious vaccine are mitigated; the risks of using a placebo control are justified by the social and public health value of the research; and the research is responsive to local health needs. The four situations are: (1) developing a locally affordable vaccine, (2) evaluating the local safety and efficacy of an existing vaccine, (3) testing a new vaccine when an existing vaccine is considered inappropriate for local use (e.g. based on epidemiologic or demographic factors), and (4) determining the local burden of disease. PMID:24768580

What's new in tuberculosis vaccines?

PubMed Central

Ginsberg, Ann M.

2002-01-01

Over the past 10 years, tuberculosis (TB) vaccine development has resurged as an active area of investigation. The renewed interest has been stimulated by the recognition that, although BCG is delivered to approximately 90% of all neonates globally through the Expanded Programme on Immunization, Mycobacterium tuberculosis continues to cause over 8 million new cases of TB and over 2 million deaths annually. Over one hundred TB vaccine candidates have been developed, using different approaches to inducing protective immunity. Candidate vaccines are typically screened in small animal models of primary TB disease for their ability to protect against a virulent strain of M. tuberculosis. The most promising are now beginning to enter human safety trials, marking real progress in this field for the first time in 80 years. PMID:12132007

PKI security in large-scale healthcare networks.

PubMed

Mantas, Georgios; Lymberopoulos, Dimitrios; Komninos, Nikos

2012-06-01

During the past few years a lot of PKI (Public Key Infrastructures) infrastructures have been proposed for healthcare networks in order to ensure secure communication services and exchange of data among healthcare professionals. However, there is a plethora of challenges in these healthcare PKI infrastructures. Especially, there are a lot of challenges for PKI infrastructures deployed over large-scale healthcare networks. In this paper, we propose a PKI infrastructure to ensure security in a large-scale Internet-based healthcare network connecting a wide spectrum of healthcare units geographically distributed within a wide region. Furthermore, the proposed PKI infrastructure facilitates the trust issues that arise in a large-scale healthcare network including multi-domain PKI infrastructures.

SIV Infection-mediated Changes in Gastrointestinal Bacterial Microbiome and Virome are Associated With Immunodeficiency and Prevented by Vaccination

PubMed Central

Handley, Scott A.; Desai, Chandni; Zhao, Guoyan; Droit, Lindsay; Monaco, Cynthia L.; Schroeder, Andrew C.; Nkolola, Joseph P.; Norman, Megan E.; Miller, Andrew D.; Wang, David; Barouch, Dan H.; Virgin, Herbert W.

2016-01-01

SUMMARY AIDS caused by simian immunodeficiency virus (SIV) infection is associated with gastrointestinal disease, systemic immune activation and, in cross sectional studies, changes in the enteric virome. Here we performed a longitudinal study of a vaccine cohort to define the natural history of changes in the fecal metagenome in SIV-infected monkeys. Matched rhesus macaques were either uninfected or intrarectally challenged with SIV, with a subset receiving the Ad26 vaccine, an adenovirus vector expressing the viral Env/Gag/Pol antigens. Progression of SIV infection to AIDS was associated with increased detection of potentially pathogenic viruses and bacterial enteropathogens. Specifically, adenoviruses were associated with an increased incidence of gastrointestinal disease and AIDS-related mortality. Viral and bacterial enteropathogens were largely absent from animals protected by the vaccine. These data suggest that the SIV-associated gastrointestinal disease is associated with the presence of both viral and bacterial enteropathogens and protection against SIV infection by vaccination prevents enteropathogen emergence. PMID:26962943

Optimization and scale-up of cell culture and purification processes for production of an adenovirus-vectored tuberculosis vaccine candidate.

PubMed

Shen, Chun Fang; Jacob, Danielle; Zhu, Tao; Bernier, Alice; Shao, Zhongqi; Yu, Xuefeng; Patel, Mehul; Lanthier, Stephane; Kamen, Amine

2016-06-17

Tuberculosis (TB) is the second leading cause of death by infectious disease worldwide. The only available TB vaccine is the Bacille Calmette-Guerin (BCG). However, parenterally administered Mycobacterium bovis BCG vaccine confers only limited immune protection from pulmonary tuberculosis in humans. There is a need for developing effective boosting vaccination strategies. AdAg85A, an adenoviral vector expressing the mycobacterial protein Ag85A, is a new tuberculosis vaccine candidate, and has shown promising results in pre-clinical studies and phase I trial. This adenovirus vectored vaccine is produced using HEK 293 cell culture. Here we report on the optimization of cell culture conditions, scale-up of production and purification of the AdAg85A at different scales. Four commercial serum-free media were evaluated under various conditions for supporting the growth of HEK293 cell and production of AdAg85A. A culturing strategy was employed to take advantages of two culture media with respective strengths in supporting the cell growth and virus production, which enabled to maintain virus productivity at higher cell densities and resulted in more than two folds of increases in culture titer. The production of AdAg85A was successfully scaled up and validated at 60L bioreactor under the optimal conditions. The AdAg85A generated from the 3L and 60L bioreactor runs was purified through several purification steps. More than 98% of total cellular proteins was removed, over 60% of viral particles was recovered after the purification process, and purity of AdAg85A was similar to that of the ATCC VR-1516 Ad5 standard. Vaccination of mice with the purified AdAg85A demonstrated a very good level of Ag85A-specific antibody responses. The optimized production and purification conditions were transferred to a GMP facility for manufacturing of AdAg85A for generation of clinical grade material to support clinical trials. Crown Copyright © 2016. Published by Elsevier Ltd. All rights

An update on vaccines for tuberculosis - there is more to it than just waning of BCG efficacy with time.

PubMed

Romano, Marta; Huygen, Kris

2012-12-01

Apart from better diagnostics and new anti-microbial drugs, an effective vaccine for tuberculosis is urgently needed to halt this poverty-related disease, afflicting millions of people worldwide. After a general introduction on the global threat of tuberculosis, the pros and cons of the existing M. bovis BCG vaccine are discussed. As the correlates of protection against tuberculosis remain largely unknown, new findings in biomarker research are described. Next, an update on the ongoing Phase I and Phase II clinical trials is given. Finally, some of the most promising novel pre-clinical developments using live attenuated vaccines, sub-unit vaccines, prime-boost strategies, and new vaccination routes are discussed. The field has made considerable progress and 12 vaccine candidates have now actually entered Phase I or Phase IIa and IIb clinical trials. It is argued that the variable protection conferred by the existing BCG vaccine against reactivation of latent TB is caused not only by waning of its efficacy with time but also by its weak induction of MHC class I restricted responses. Prime-boost strategies based on the actual BCG vaccine may not be sufficient to overcome this hurdle. The use of plasmid DNA vaccination might offer a solution.

Large-scale velocities and primordial non-Gaussianity

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

Schmidt, Fabian

2010-09-15

We study the peculiar velocities of density peaks in the presence of primordial non-Gaussianity. Rare, high-density peaks in the initial density field can be identified with tracers such as galaxies and clusters in the evolved matter distribution. The distribution of relative velocities of peaks is derived in the large-scale limit using two different approaches based on a local biasing scheme. Both approaches agree, and show that halos still stream with the dark matter locally as well as statistically, i.e. they do not acquire a velocity bias. Nonetheless, even a moderate degree of (not necessarily local) non-Gaussianity induces a significant skewnessmore » ({approx}0.1-0.2) in the relative velocity distribution, making it a potentially interesting probe of non-Gaussianity on intermediate to large scales. We also study two-point correlations in redshift space. The well-known Kaiser formula is still a good approximation on large scales, if the Gaussian halo bias is replaced with its (scale-dependent) non-Gaussian generalization. However, there are additional terms not encompassed by this simple formula which become relevant on smaller scales (k > or approx. 0.01h/Mpc). Depending on the allowed level of non-Gaussianity, these could be of relevance for future large spectroscopic surveys.« less

Oral Vaccination with a DNA Vaccine Encoding Capsid Protein of Duck Tembusu Virus Induces Protection Immunity

PubMed Central

Shen, Haoyue; Jia, Renyong; Wang, Mingshu; Chen, Shun; Zhu, Dekang; Liu, Mafeng; Zhao, Xinxin; Yang, Qiao; Wu, Ying; Liu, Yunya; Zhang, Ling; Yin, Zhongqiong; Jing, Bo

2018-01-01

The emergence of duck tembusu virus (DTMUV), a new member of the Flavivirus genus, has caused great economical loss in the poultry industry in China. Since the outbreak and spread of DTMUV is hard to control in a clinical setting, an efficient and low-cost oral delivery DNA vaccine SL7207 (pVAX1-C) based on the capsid protein of DTMUV was developed and evaluated in this study. The antigen capsid protein was expressed from the DNA vaccine SL7207 (pVAX1-C), both in vitro and in vivo. The humoral and cellular immune responses in vivo were observed after oral immunization with the SL7207 (pVAX1-C) DNA vaccine. High titers of the specific antibody against the capsid protein and the neutralizing antibody against the DTMUV virus were both detected after inoculation. The ducks were efficiently protected from lethal DTMUV exposure by the SL7207 (pVAX1-C) vaccine in this experiment. Taken together, we demonstrated that the capsid protein of DTMUV possesses a strong immunogenicity against the DTMUV infection. Moreover, an oral delivery of the DNA vaccine SL7207 (pVAX1-C) utilizing Salmonella SL7207 was an efficient way to protect the ducks against DTMUV infection and provides an economic and fast vaccine delivery strategy for a large scale clinical use. PMID:29642401

Delivering vaccines to the people who need them most

PubMed Central

Barocchi, Michèle Anne; Rappuoli, Rino

2015-01-01

Thanks to the Global Alliance for Vaccines and Immunization (GAVI), the Vaccine Fund and the Bill & Melinda Gates Foundation, the global health community has made enormous progress in providing already existing vaccines to developing countries. However, there still exists a gap to develop vaccines for which there is no market in the Western world, owing to low economic incentives for the private sector to justify the investments necessary for vaccine development. In many cases, industry has the technologies, but lacks the impetus to direct resources to develop these vaccine products. The present emergency with the Ebola vaccine provides us an excellent example where a vaccine was feasible several years ago, but the global health community waited for a humanitarian disaster to direct efforts and resources to develop this vaccine. In the beginning of 2015, the first large-scale trials of two experimental vaccines against Ebola virus disease have begun in West Africa. During the past few years, several institutions have dedicated efforts to the development of vaccines against diseases present only in low-income countries. These include the International Vaccine Institute, the Novartis Vaccines Institute for Global Health, the Hilleman Institute, the Sabin Vaccine Institute and the Infectious Disease Research Institute. Nevertheless, solving this problem requires a more significant global effort than that currently invested. These efforts include a clear policy, global coordination of funds dedicated to the development of neglected disease and an agreement on regulatory strategies and incentives for the private sector. PMID:25964460

Synthetic peptide vaccine against Taenia solium pig cysticercosis: successful vaccination in a controlled field trial in rural Mexico.

PubMed

Huerta, M; de Aluja, A S; Fragoso, G; Toledo, A; Villalobos, N; Hernández, M; Gevorkian, G; Acero, G; Díaz, A; Alvarez, I; Avila, R; Beltrán, C; Garcia, G; Martinez, J J; Larralde, C; Sciutto, E

2001-10-12

Taenia solium cysticercosis seriously affects human health when localised in the central nervous system (CNS) and causes great economic loss in pig husbandry in rural areas of endemic countries. Increasing the resistance to the parasite in the obligatory host pig may help in curbing transmission. Three synthetic peptides based on protein sequences of the murine parasite Taenia crassiceps, which had previously been shown to induce protection in mice against homologous challenge, were tested as a vaccine against T. solium cysticercosis in pigs. Vaccinated and unvaccinated piglets (240 in all) were distributed in pairs among the peasants' households of two rural villages in Mexico in which 14% of the native pigs were cysticercotic. Ten to twelve months later, the effect of vaccination was evaluated at necropsy. Vaccination decreased the total number of T. solium cysticerci (98.7%) and reduced the prevalence (52.6%). The natural challenge conditions used in this field trial strengthen the likelihood of successful transmission control to both pig and human through a large-scale pig vaccination program. We believe this is a major contribution in anticysticercosis vaccine development as these rather simple yet protective peptides are potentially more cost-effective to produce and less variable in results than antigens that are more complex.

Paradox of vaccination: is vaccination really effective against avian flu epidemics?

PubMed

Iwami, Shingo; Suzuki, Takafumi; Takeuchi, Yasuhiro

2009-01-01

Although vaccination can be a useful tool for control of avian influenza epidemics, it might engender emergence of a vaccine-resistant strain. Field and experimental studies show that some avian influenza strains acquire resistance ability against vaccination. We investigated, in the context of the emergence of a vaccine-resistant strain, whether a vaccination program can prevent the spread of infectious disease. We also investigated how losses from immunization by vaccination imposed by the resistant strain affect the spread of the disease. We designed and analyzed a deterministic compartment model illustrating transmission of vaccine-sensitive and vaccine-resistant strains during a vaccination program. We investigated how the loss of protection effectiveness impacts the program. Results show that a vaccination to prevent the spread of disease can instead spread the disease when the resistant strain is less virulent than the sensitive strain. If the loss is high, the program does not prevent the spread of the resistant strain despite a large prevalence rate of the program. The epidemic's final size can be larger than that before the vaccination program. We propose how to use poor vaccines, which have a large loss, to maximize program effects and describe various program risks, which can be estimated using available epidemiological data. We presented clear and simple concepts to elucidate vaccination program guidelines to avoid negative program effects. Using our theory, monitoring the virulence of the resistant strain and investigating the loss caused by the resistant strain better development of vaccination strategies is possible.

Enteritis

MedlinePlus

... enteritis E coli enteritis Food poisoning Radiation enteritis Salmonella enteritis Shigella enteritis Staph aureus food poisoning Symptoms ... store food that needs to stay chilled. Images Salmonella typhi organism Yersinia enterocolitica organism Campylobacter jejuni organism ...

Large-scale regions of antimatter

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

Grobov, A. V., E-mail: alexey.grobov@gmail.com; Rubin, S. G., E-mail: sgrubin@mephi.ru

2015-07-15

Amodified mechanism of the formation of large-scale antimatter regions is proposed. Antimatter appears owing to fluctuations of a complex scalar field that carries a baryon charge in the inflation era.

Vaccination status and prevalence of enteric viruses in internationally adopted children. The case of Parma, Italy.

PubMed

Veronesi, Licia; Virdis, Raffaele; Bizzoco, Sabrina; Colucci, Maria Eugenia; Affanni, Paola; Paganuzzi, Francesca; Riccò, Matteo; Capobianco, Emanuela; Tanzi, Maria Luisa

2011-12-01

On age basis, internationally adopted children may have begun or fully completed all required vaccinations, but official documentation from original Countries is frequently insufficient. Aims of this study were to evaluate the seroprotection rate for tuberculosis, hepatitis B, poliomyelitis and tetanus according to immunization cards in 67 children recently adopted and to test the prevalence of enterovirus on faecal specimens. Seroprotection and vaccination status were frequently inconsistent and these results confirm that immunitary surveillance is a cornerstone for the prevention of diseases for which a vaccination is available. (www.actabiomedica.it).

Virus-like particle (VLP)-based vaccines for pandemic influenza

PubMed Central

López-Macías, Constantino

2012-01-01

The influenza pandemic of 2009 demonstrated the inability of the established global capacity for egg-based vaccine production technology to provide sufficient vaccine for the population in a timely fashion. Several alternative technologies for developing influenza vaccines have been proposed, among which non-replicating virus-like particles (VLPs) represent an attractive option because of their safety and immunogenic characteristics. VLP vaccines against pandemic influenza have been developed in tobacco plant cells and in Sf9 insect cells infected with baculovirus that expresses protein genes from pandemic influenza strains. These technologies allow rapid and large-scale production of vaccines (3–12 weeks). The 2009 influenza outbreak provided an opportunity for clinical testing of a pandemic influenza VLP vaccine in the midst of the outbreak at its epicenter in Mexico. An influenza A(H1N1)2009 VLP pandemic vaccine (produced in insect cells) was tested in a phase II clinical trial involving 4,563 healthy adults. Results showed that the vaccine is safe and immunogenic despite high preexisting anti-A(H1N1)2009 antibody titers present in the population. The safety and immunogenicity profile presented by this pandemic VLP vaccine during the outbreak in Mexico suggests that VLP technology is a suitable alternative to current influenza vaccine technologies for producing pandemic and seasonal vaccines. PMID:22330956

Epidemiological Surveillance as a Basis for Vaccine Trials. Establishment of a Vaccine Evaluation Unit

DTIC Science & Technology

1993-05-01

hepatitis (A, B and non-A non-B), infectious mononucleosis and cytomegalovirus infection. IMMUNOGENICITY STUDIES A randomized, partly blinded...Klebsiella, Pseudomonas). Enterics, Foreign, Hepatitis A, Hepatitis B, Infectious Diseases, Vaccines, Biotechnology, ID, RA I Unclassified Unclassified...INTRODUCTION MILITARY IMPORTANCE OF THE STUDY AND MEDICAL APPLICATIONS A number of infectious diseases are of particular importance in military

Towards large scale multi-target tracking

NASA Astrophysics Data System (ADS)

Vo, Ba-Ngu; Vo, Ba-Tuong; Reuter, Stephan; Lam, Quang; Dietmayer, Klaus

2014-06-01

Multi-target tracking is intrinsically an NP-hard problem and the complexity of multi-target tracking solutions usually do not scale gracefully with problem size. Multi-target tracking for on-line applications involving a large number of targets is extremely challenging. This article demonstrates the capability of the random finite set approach to provide large scale multi-target tracking algorithms. In particular it is shown that an approximate filter known as the labeled multi-Bernoulli filter can simultaneously track one thousand five hundred targets in clutter on a standard laptop computer.

The Expanded Large Scale Gap Test

DTIC Science & Technology

1987-03-01

NSWC TR 86-32 DTIC THE EXPANDED LARGE SCALE GAP TEST BY T. P. LIDDIARD D. PRICE RESEARCH AND TECHNOLOGY DEPARTMENT ’ ~MARCH 1987 Ap~proved for public...arises, to reduce the spread in the LSGT 50% gap value.) The worst charges, such as those with the highest or lowest densities, the largest re-pressed...Arlington, VA 22217 PE 62314N INS3A 1 RJ14E31 7R4TBK 11 TITLE (Include Security CIlmsilficatiorn The Expanded Large Scale Gap Test . 12. PEIRSONAL AUTHOR() T

An informal paper on large-scale dynamic systems

NASA Technical Reports Server (NTRS)

Ho, Y. C.

1975-01-01

Large scale systems are defined as systems requiring more than one decision maker to control the system. Decentralized control and decomposition are discussed for large scale dynamic systems. Information and many-person decision problems are analyzed.

The burden and characteristics of enteric fever at a healthcare facility in a densely populated area of Kathmandu.

PubMed

Karkey, Abhilasha; Arjyal, Amit; Anders, Katherine L; Boni, Maciej F; Dongol, Sabina; Koirala, Samir; My, Phan Vu Tra; Nga, Tran Vu Thieu; Clements, Archie C A; Holt, Kathryn E; Duy, Pham Thanh; Day, Jeremy N; Campbell, James I; Dougan, Gordon; Dolecek, Christiane; Farrar, Jeremy; Basnyat, Buddha; Baker, Stephen

2010-11-15

Enteric fever, caused by Salmonella enterica serovars Typhi and Paratyphi A (S. Typhi and S. Paratyphi A) remains a major public health problem in many settings. The disease is limited to locations with poor sanitation which facilitates the transmission of the infecting organisms. Efficacious and inexpensive vaccines are available for S. Typhi, yet are not commonly deployed to control the disease. Lack of vaccination is due partly to uncertainty of the disease burden arising from a paucity of epidemiological information in key locations. We have collected and analyzed data from 3,898 cases of blood culture-confirmed enteric fever from Patan Hospital in Lalitpur Sub-Metropolitan City (LSMC), between June 2005 and May 2009. Demographic data was available for a subset of these patients (n = 527) that were resident in LSMC and who were enrolled in trials. We show a considerable burden of enteric fever caused by S. Typhi (2,672; 68.5%) and S. Paratyphi A (1,226; 31.5%) at this Hospital over a four year period, which correlate with seasonal fluctuations in rainfall. We found that local population density was not related to incidence and we identified a focus of infections in the east of LSMC. With data from patients resident in LSMC we found that the median age of those with S. Typhi (16 years) was significantly less than S. Paratyphi A (20 years) and that males aged 15 to 25 were disproportionately infected. Our findings provide a snapshot into the epidemiological patterns of enteric fever in Kathmandu. The uneven distribution of enteric fever patients within the population suggests local variation in risk factors, such as contaminated drinking water. These findings are important for initiating a vaccination scheme and improvements in sanitation. We suggest any such intervention should be implemented throughout the LSMC area.

On large-scale dynamo action at high magnetic Reynolds number

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

Cattaneo, F.; Tobias, S. M., E-mail: smt@maths.leeds.ac.uk

2014-07-01

We consider the generation of magnetic activity—dynamo waves—in the astrophysical limit of very large magnetic Reynolds number. We consider kinematic dynamo action for a system consisting of helical flow and large-scale shear. We demonstrate that large-scale dynamo waves persist at high Rm if the helical flow is characterized by a narrow band of spatial scales and the shear is large enough. However, for a wide band of scales the dynamo becomes small scale with a further increase of Rm, with dynamo waves re-emerging only if the shear is then increased. We show that at high Rm, the key effect ofmore » the shear is to suppress small-scale dynamo action, allowing large-scale dynamo action to be observed. We conjecture that this supports a general 'suppression principle'—large-scale dynamo action can only be observed if there is a mechanism that suppresses the small-scale fluctuations.« less

Large-scale dynamos in rapidly rotating plane layer convection

NASA Astrophysics Data System (ADS)

Bushby, P. J.; Käpylä, P. J.; Masada, Y.; Brandenburg, A.; Favier, B.; Guervilly, C.; Käpylä, M. J.

2018-05-01

Context. Convectively driven flows play a crucial role in the dynamo processes that are responsible for producing magnetic activity in stars and planets. It is still not fully understood why many astrophysical magnetic fields have a significant large-scale component. Aims: Our aim is to investigate the dynamo properties of compressible convection in a rapidly rotating Cartesian domain, focusing upon a parameter regime in which the underlying hydrodynamic flow is known to be unstable to a large-scale vortex instability. Methods: The governing equations of three-dimensional non-linear magnetohydrodynamics (MHD) are solved numerically. Different numerical schemes are compared and we propose a possible benchmark case for other similar codes. Results: In keeping with previous related studies, we find that convection in this parameter regime can drive a large-scale dynamo. The components of the mean horizontal magnetic field oscillate, leading to a continuous overall rotation of the mean field. Whilst the large-scale vortex instability dominates the early evolution of the system, the large-scale vortex is suppressed by the magnetic field and makes a negligible contribution to the mean electromotive force that is responsible for driving the large-scale dynamo. The cycle period of the dynamo is comparable to the ohmic decay time, with longer cycles for dynamos in convective systems that are closer to onset. In these particular simulations, large-scale dynamo action is found only when vertical magnetic field boundary conditions are adopted at the upper and lower boundaries. Strongly modulated large-scale dynamos are found at higher Rayleigh numbers, with periods of reduced activity (grand minima-like events) occurring during transient phases in which the large-scale vortex temporarily re-establishes itself, before being suppressed again by the magnetic field.

Vaccine production, distribution, access, and uptake.

PubMed

Smith, Jon; Lipsitch, Marc; Almond, Jeffrey W

2011-07-30

For human vaccines to be available on a global scale, complex production methods, meticulous quality control, and reliable distribution channels are needed to ensure that the products are potent and effective at the point of use. The technologies used to manufacture different types of vaccines can strongly affect vaccine cost, ease of industrial scale-up, stability, and, ultimately, worldwide availability. The complexity of manufacturing is compounded by the need for different formulations in different countries and age-groups. Reliable vaccine production in appropriate quantities and at affordable prices is the cornerstone of developing global vaccination policies. However, to ensure optimum access and uptake, strong partnerships are needed between private manufacturers, regulatory authorities, and national and international public health services. For vaccines whose supply is insufficient to meet demand, prioritisation of target groups can increase the effect of these vaccines. In this report, we draw from our experience of vaccine development and focus on influenza vaccines as an example to consider production, distribution, access, and other factors that affect vaccine uptake and population-level effectiveness. Copyright © 2011 Elsevier Ltd. All rights reserved.

Quantitative assessment of the risk of rabies entering Japan through the importation of dogs and cats from the USA.

PubMed

Kamakawa, H; Koiwai, M; Satomura, S; Eto, M; Sugiura, K

2009-08-01

Up to October 2004, dogs and cats imported into Japan were subjected to a quarantine regimen which consisted of vaccination and a 30- to 365-day waiting period in the country of origin and a 14-day quarantine period upon arrival in Japan. This regimen was replaced by a new one, consisting of vaccination, antibody level titration and a 180-day waiting period in the country of origin, in November 2004. To evaluate the effect of this policy change, a quantitative risk assessment was undertaken. The risk of rabies entering Japan through the importation of dogs and cats from the USA under the old - and new - regimens was quantitatively assessed and compared. Under the new regimen, rabies will enter Japan once every 4932 years (90% confidence interval 1812-13 412 years) through the importation of dogs and cats from the USA. Under the old regimen, rabies would enter Japan once every 70 years (39-205 years), 83 years (45-267 years) or 190 years (104-609 years) assuming that the animal departs the country of origin 30 days, 180 days or 365 days after vaccination, respectively. This indicates the policy change would reduce the risk by a factor of 1/25-1/70.

African Swine Fever Virus Biology and Vaccine Approaches.

PubMed

Revilla, Yolanda; Pérez-Núñez, Daniel; Richt, Juergen A

2018-01-01

African swine fever (ASF) is an acute and often fatal disease affecting domestic pigs and wild boar, with severe economic consequences for affected countries. ASF is endemic in sub-Saharan Africa and the island of Sardinia, Italy. Since 2007, the virus emerged in the republic of Georgia, and since then spread throughout the Caucasus region and Russia. Outbreaks have also been reported in Belarus, Ukraine, Lithuania, Latvia, Estonia, Romania, Moldova, Czech Republic, and Poland, threatening neighboring West European countries. The causative agent, the African swine fever virus (ASFV), is a large, enveloped, double-stranded DNA virus that enters the cell by macropinocytosis and a clathrin-dependent mechanism. African Swine Fever Virus is able to interfere with various cellular signaling pathways resulting in immunomodulation, thus making the development of an efficacious vaccine very challenging. Inactivated preparations of African Swine Fever Virus do not confer protection, and the role of antibodies in protection remains unclear. The use of live-attenuated vaccines, although rendering suitable levels of protection, presents difficulties due to safety and side effects in the vaccinated animals. Several African Swine Fever Virus proteins have been reported to induce neutralizing antibodies in immunized pigs, and vaccination strategies based on DNA vaccines and recombinant proteins have also been explored, however, without being very successful. The complexity of the virus particle and the ability of the virus to modulate host immune responses are most likely the reason for this failure. Furthermore, no permanent cell lines able to sustain productive virus infection by both virulent and naturally attenuated African Swine Fever Virus strains exist so far, thus impairing basic research and the commercial production of attenuated vaccine candidates. © 2018 Elsevier Inc. All rights reserved.

Large-scale anisotropy of the cosmic microwave background radiation

NASA Technical Reports Server (NTRS)

Silk, J.; Wilson, M. L.

1981-01-01

Inhomogeneities in the large-scale distribution of matter inevitably lead to the generation of large-scale anisotropy in the cosmic background radiation. The dipole, quadrupole, and higher order fluctuations expected in an Einstein-de Sitter cosmological model have been computed. The dipole and quadrupole anisotropies are comparable to the measured values, and impose important constraints on the allowable spectrum of large-scale matter density fluctuations. A significant dipole anisotropy is generated by the matter distribution on scales greater than approximately 100 Mpc. The large-scale anisotropy is insensitive to the ionization history of the universe since decoupling, and cannot easily be reconciled with a galaxy formation theory that is based on primordial adiabatic density fluctuations.

Economically viable large-scale hydrogen liquefaction

NASA Astrophysics Data System (ADS)

Cardella, U.; Decker, L.; Klein, H.

2017-02-01

The liquid hydrogen demand, particularly driven by clean energy applications, will rise in the near future. As industrial large scale liquefiers will play a major role within the hydrogen supply chain, production capacity will have to increase by a multiple of today’s typical sizes. The main goal is to reduce the total cost of ownership for these plants by increasing energy efficiency with innovative and simple process designs, optimized in capital expenditure. New concepts must ensure a manageable plant complexity and flexible operability. In the phase of process development and selection, a dimensioning of key equipment for large scale liquefiers, such as turbines and compressors as well as heat exchangers, must be performed iteratively to ensure technological feasibility and maturity. Further critical aspects related to hydrogen liquefaction, e.g. fluid properties, ortho-para hydrogen conversion, and coldbox configuration, must be analysed in detail. This paper provides an overview on the approach, challenges and preliminary results in the development of efficient as well as economically viable concepts for large-scale hydrogen liquefaction.

Large-Scale Coronal Heating from the Solar Magnetic Network

NASA Technical Reports Server (NTRS)

Falconer, David A.; Moore, Ronald L.; Porter, Jason G.; Hathaway, David H.

1999-01-01

In Fe 12 images from SOHO/EIT, the quiet solar corona shows structure on scales ranging from sub-supergranular (i.e., bright points and coronal network) to multi- supergranular. In Falconer et al 1998 (Ap.J., 501, 386) we suppressed the large-scale background and found that the network-scale features are predominantly rooted in the magnetic network lanes at the boundaries of the supergranules. The emission of the coronal network and bright points contribute only about 5% of the entire quiet solar coronal Fe MI emission. Here we investigate the large-scale corona, the supergranular and larger-scale structure that we had previously treated as a background, and that emits 95% of the total Fe XII emission. We compare the dim and bright halves of the large- scale corona and find that the bright half is 1.5 times brighter than the dim half, has an order of magnitude greater area of bright point coverage, has three times brighter coronal network, and has about 1.5 times more magnetic flux than the dim half These results suggest that the brightness of the large-scale corona is more closely related to the large- scale total magnetic flux than to bright point activity. We conclude that in the quiet sun: (1) Magnetic flux is modulated (concentrated/diluted) on size scales larger than supergranules. (2) The large-scale enhanced magnetic flux gives an enhanced, more active, magnetic network and an increased incidence of network bright point formation. (3) The heating of the large-scale corona is dominated by more widespread, but weaker, network activity than that which heats the bright points. This work was funded by the Solar Physics Branch of NASA's office of Space Science through the SR&T Program and the SEC Guest Investigator Program.

Improving rotavirus vaccine coverage: Can newer-generation and locally produced vaccines help?

PubMed Central

Kanungo, Suman; Anh, Dang Duc; Grais, Rebecca F.

2018-01-01

ABSTRACT There are two internationally available WHO-prequalified oral rotavirus vaccines (Rotarix and RotaTeq), two rotavirus vaccines licensed in India (Rotavac and Rotasiil), one in China (Lanzhou lamb rotavirus vaccine) and one in Vietnam (Rotavin-M1), and several candidates in development. Rotavirus vaccination has been rolled out in Latin American countries and is beginning to be deployed in sub-Saharan African countries but middle- and low-income Asian countries have lagged behind in rotavirus vaccine introduction. We provide a mini-review of the leading newer-generation rotavirus vaccines and compare them with Rotarix and RotaTeq. We discuss how the development and future availability of newer-generation rotavirus vaccines that address the programmatic needs of poorer countries may help scale-up rotavirus vaccination where it is needed. PMID:29135339

Large- and Very-Large-Scale Motions in Katabatic Flows Over Steep Slopes

NASA Astrophysics Data System (ADS)

Giometto, M. G.; Fang, J.; Salesky, S.; Parlange, M. B.

2016-12-01

Evidence of large- and very-large-scale motions populating the boundary layer in katabatic flows over steep slopes is presented via direct numerical simulations (DNSs). DNSs are performed at a modified Reynolds number (Rem = 967), considering four sloping angles (α = 60°, 70°, 80° and 90°). Large coherent structures prove to be strongly dependent on the inclination of the underlying surface. Spectra and co-spectra consistently show signatures of large-scale motions (LSMs), with streamwise extension on the order of the boundary layer thickness. A second low-wavenumber mode characterizes pre-multiplied spectra and co-spectra when the slope angle is below 70°, indicative of very-large-scale motions (VLSMs). In addition, conditional sampling and averaging shows how LSMs and VLSMs are induced by counter-rotating roll modes, in agreement with findings from canonical wall-bounded flows. VLSMs contribute to the stream-wise velocity variance and shear stress in the above-jet regions up to 30% and 45% respectively, whereas both LSMs and VLSMs are inactive in the near-wall regions.

Mucosal Vaccination against Tuberculosis Using Inert Bioparticles

PubMed Central

Reljic, Rajko; Sibley, Laura; Huang, Jen-Min; Pepponi, Ilaria; Hoppe, Andreas; Hong, Huynh A.

2013-01-01

Needle-free, mucosal immunization is a highly desirable strategy for vaccination against many pathogens, especially those entering through the respiratory mucosa, such as Mycobacterium tuberculosis. Unfortunately, mucosal vaccination against tuberculosis (TB) is impeded by a lack of suitable adjuvants and/or delivery platforms that could induce a protective immune response in humans. Here, we report on a novel biotechnological approach for mucosal vaccination against TB that overcomes some of the current limitations. This is achieved by coating protective TB antigens onto the surface of inert bacterial spores, which are then delivered to the respiratory tract. Our data showed that mice immunized nasally with coated spores developed humoral and cellular immune responses and multifunctional T cells and, most importantly, presented significantly reduced bacterial loads in their lungs and spleens following pathogenic challenge. We conclude that this new vaccine delivery platform merits further development as a mucosal vaccine for TB and possibly also other respiratory pathogens. PMID:23959722

Considerations around the introduction of a cholera vaccine in Bangladesh.

PubMed

Nelson, Christopher B; Mogasale, Vittal; Bari, Tajul Islam A; Clemens, John D

2014-12-12

Cholera is an endemic and epidemic disease in Bangladesh. On 3 March 2013, a meeting on cholera and cholera vaccination in Bangladesh was convened by the Foundation Mérieux jointly with the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR, B). The purpose of the meeting was to discuss the investment case for cholera vaccination as a complimentary control and prevention strategy. The performance of a new low cost oral cholera vaccine, Shanchol™, used in recent trials in Bangladesh, was also reviewed in the context of a potential large-scale public-sector vaccination program. Findings showed the oral vaccine to be highly cost-effective when targeting ages 1-14 y, and cost-effective when targeting ages 1+y, in high-burden/high-risk districts. Other vaccination strategies targeting urban slums and rural areas without improved water were found to be cost-effective. Regardless of cost-effectiveness (value), the budget impact (affordability) will be an important determinant of which target population and vaccination strategy is selected. Most importantly, adequate vaccine supply for the proposed vaccination programs must be addressed in the context of global efforts to establish a cholera vaccine stockpile and supply other control and prevention efforts. Copyright © 2014. Published by Elsevier Ltd.. All rights reserved.

Dengue vaccine: WHO position paper, July 2016 - recommendations.

PubMed

World Health Organization

2017-03-01

This article presents the World Health Organization's (WHO) recommendations on the use of dengue vaccine excerpted from the WHO position paper on dengue vaccine published in the Weekly epidemiological Record in July 2016 (Dengue vaccine: WHO position paper, 2016) [1]. The current document is the first WHO position paper on dengue vaccination and focuses primarily on the available evidence concerning the only dengue vaccine to have been registered by National Regulatory Authorities. The position paper gives consideration to the epidemiological features of the disease and assesses the potential use of the vaccine for public health benefits. Footnotes to this paper provide a number of core references including references to grading tables that assess the quality of the scientific evidence, and to the evidence-to-recommendation table. In accordance with its mandate to provide guidance to Member States on health policy matters, WHO issues a series of regularly updated position papers on vaccines and combinations of vaccines against diseases that have an international public health impact. These papers are concerned primarily with the use of vaccines in large-scale immunization programmes; they summarize essential background information on diseases and vaccines, and conclude with WHO's current position on the use of vaccines in the global context. This paper reflects the recommendations of the WHO's Strategic Advisory Group of Experts (SAGE) on immunization. Recommendations on the use of this dengue vaccine were discussed by SAGE in April 2016; evidence presented at that SAGE meeting can be accessed at: http://www.who.int/immunization/sage/previous/en/index.html. Copyright © 2016 Elsevier Ltd. All rights reserved.

Large Scale Processes and Extreme Floods in Brazil

NASA Astrophysics Data System (ADS)

Ribeiro Lima, C. H.; AghaKouchak, A.; Lall, U.

2016-12-01

Persistent large scale anomalies in the atmospheric circulation and ocean state have been associated with heavy rainfall and extreme floods in water basins of different sizes across the world. Such studies have emerged in the last years as a new tool to improve the traditional, stationary based approach in flood frequency analysis and flood prediction. Here we seek to advance previous studies by evaluating the dominance of large scale processes (e.g. atmospheric rivers/moisture transport) over local processes (e.g. local convection) in producing floods. We consider flood-prone regions in Brazil as case studies and the role of large scale climate processes in generating extreme floods in such regions is explored by means of observed streamflow, reanalysis data and machine learning methods. The dynamics of the large scale atmospheric circulation in the days prior to the flood events are evaluated based on the vertically integrated moisture flux and its divergence field, which are interpreted in a low-dimensional space as obtained by machine learning techniques, particularly supervised kernel principal component analysis. In such reduced dimensional space, clusters are obtained in order to better understand the role of regional moisture recycling or teleconnected moisture in producing floods of a given magnitude. The convective available potential energy (CAPE) is also used as a measure of local convection activities. We investigate for individual sites the exceedance probability in which large scale atmospheric fluxes dominate the flood process. Finally, we analyze regional patterns of floods and how the scaling law of floods with drainage area responds to changes in the climate forcing mechanisms (e.g. local vs large scale).

Reasons for measles cases not being vaccinated with MMR: investigation into parents' and carers' views following a large measles outbreak.

PubMed

McHale, P; Keenan, A; Ghebrehewet, S

2016-03-01

Uptake rates for the combined measles, mumps and rubella (MMR) vaccine have been below the required 95% in the UK since a retracted and discredited article linking the MMR vaccine with autism and inflammatory bowel disease was released in 1998. This study undertook semi-structured telephone interviews among parents or carers of 47 unvaccinated measles cases who were aged between 13 months and 9 years, during a large measles outbreak in Merseyside. Results showed that concerns over the specific links with autism remain an important cause of refusal to vaccinate, with over half of respondents stating this as a reason. A quarter stated child illness during scheduled vaccination time, while other reasons included general safety concerns and access issues. Over half of respondents felt that more information or a discussion with a health professional would help the decision-making process, while a third stated improved access. There was clear support for vaccination among respondents when asked about current opinions regarding MMR vaccine. The findings support the hypothesis that safety concerns remain a major barrier to MMR vaccination, and also support previous evidence that experience of measles is an important determinant in the decision to vaccinate.

Generation of large-scale density fluctuations by buoyancy

NASA Technical Reports Server (NTRS)

Chasnov, J. R.; Rogallo, R. S.

1990-01-01

The generation of fluid motion from a state of rest by buoyancy forces acting on a homogeneous isotropic small-scale density field is considered. Nonlinear interactions between the generated fluid motion and the initial isotropic small-scale density field are found to create an anisotropic large-scale density field with spectrum proportional to kappa(exp 4). This large-scale density field is observed to result in an increasing Reynolds number of the fluid turbulence in its final period of decay.

Scaling up cervical cancer screening in the midst of human papillomavirus vaccination advocacy in Thailand.

PubMed

Yothasamut, Jomkwan; Putchong, Choenkwan; Sirisamutr, Teera; Teerawattananon, Yot; Tantivess, Sripen

2010-07-02

Screening tests for cervical cancer are effective in reducing the disease burden. In Thailand, a Pap smear program has been implemented throughout the country for 40 years. In 2008 the Ministry of Public Health (MoPH) unexpectedly decided to scale up the coverage of free cervical cancer screening services, to meet an ambitious target. This study analyzes the processes and factors that drove this policy innovation in the area of cervical cancer control in Thailand. In-depth interviews with key policy actors and review of relevant documents were conducted in 2009. Data analysis was guided by a framework, developed on public policy models and existing literature on scaling-up health care interventions. Between 2006 and 2008 international organizations and the vaccine industry advocated the introduction of Human Papillomavirus (HPV) vaccine for the primary prevention of cervical cancer. Meanwhile, a local study suggested that the vaccine was considerably less cost-effective than cervical cancer screening in the Thai context. Then, from August to December 2008, the MoPH carried out a campaign to expand the coverage of its cervical cancer screening program, targeting one million women. The study reveals that several factors were influential in focusing the attention of policymakers on strengthening the screening services. These included the high burden of cervical cancer in Thailand, the launch of the HPV vaccine onto the global and domestic markets, the country's political instability, and the dissemination of scientific evidence regarding the appropriateness of different options for cervical cancer prevention. Influenced by the country's political crisis, the MoPH's campaign was devised in a very short time. In the view of the responsible health officials, the campaign was not successful and indeed, did not achieve its ambitious target. The Thai case study suggests that the political crisis was a crucial factor that drew the attention of policymakers to the cervical

Scaling up cervical cancer screening in the midst of human papillomavirus vaccination advocacy in Thailand

PubMed Central

2010-01-01

Background Screening tests for cervical cancer are effective in reducing the disease burden. In Thailand, a Pap smear program has been implemented throughout the country for 40 years. In 2008 the Ministry of Public Health (MoPH) unexpectedly decided to scale up the coverage of free cervical cancer screening services, to meet an ambitious target. This study analyzes the processes and factors that drove this policy innovation in the area of cervical cancer control in Thailand. Methods In-depth interviews with key policy actors and review of relevant documents were conducted in 2009. Data analysis was guided by a framework, developed on public policy models and existing literature on scaling-up health care interventions. Results Between 2006 and 2008 international organizations and the vaccine industry advocated the introduction of Human Papillomavirus (HPV) vaccine for the primary prevention of cervical cancer. Meanwhile, a local study suggested that the vaccine was considerably less cost-effective than cervical cancer screening in the Thai context. Then, from August to December 2008, the MoPH carried out a campaign to expand the coverage of its cervical cancer screening program, targeting one million women. The study reveals that several factors were influential in focusing the attention of policymakers on strengthening the screening services. These included the high burden of cervical cancer in Thailand, the launch of the HPV vaccine onto the global and domestic markets, the country’s political instability, and the dissemination of scientific evidence regarding the appropriateness of different options for cervical cancer prevention. Influenced by the country’s political crisis, the MoPH’s campaign was devised in a very short time. In the view of the responsible health officials, the campaign was not successful and indeed, did not achieve its ambitious target. Conclusion The Thai case study suggests that the political crisis was a crucial factor that drew the

Large-Scale Aerosol Modeling and Analysis

DTIC Science & Technology

2009-09-30

Modeling of Burning Emissions ( FLAMBE ) project, and other related parameters. Our plans to embed NAAPS inside NOGAPS may need to be put on hold...AOD, FLAMBE and FAROP at FNMOC are supported by 6.4 funding from PMW-120 for “Large-scale Atmospheric Models”, “Small-scale Atmospheric Models

Information Tailoring Enhancements for Large-Scale Social Data

DTIC Science & Technology

2016-06-15

Intelligent Automation Incorporated Information Tailoring Enhancements for Large-Scale... Automation Incorporated Progress Report No. 3 Information Tailoring Enhancements for Large-Scale Social Data Submitted in accordance with...1 Work Performed within This Reporting Period .................................................... 2 1.1 Enhanced Named Entity Recognition (NER

Development of a database system for mapping insertional mutations onto the mouse genome with large-scale experimental data

PubMed Central

2009-01-01

Background Insertional mutagenesis is an effective method for functional genomic studies in various organisms. It can rapidly generate easily tractable mutations. A large-scale insertional mutagenesis with the piggyBac (PB) transposon is currently performed in mice at the Institute of Developmental Biology and Molecular Medicine (IDM), Fudan University in Shanghai, China. This project is carried out via collaborations among multiple groups overseeing interconnected experimental steps and generates a large volume of experimental data continuously. Therefore, the project calls for an efficient database system for recording, management, statistical analysis, and information exchange. Results This paper presents a database application called MP-PBmice (insertional mutation mapping system of PB Mutagenesis Information Center), which is developed to serve the on-going large-scale PB insertional mutagenesis project. A lightweight enterprise-level development framework Struts-Spring-Hibernate is used here to ensure constructive and flexible support to the application. The MP-PBmice database system has three major features: strict access-control, efficient workflow control, and good expandability. It supports the collaboration among different groups that enter data and exchange information on daily basis, and is capable of providing real time progress reports for the whole project. MP-PBmice can be easily adapted for other large-scale insertional mutation mapping projects and the source code of this software is freely available at http://www.idmshanghai.cn/PBmice. Conclusion MP-PBmice is a web-based application for large-scale insertional mutation mapping onto the mouse genome, implemented with the widely used framework Struts-Spring-Hibernate. This system is already in use by the on-going genome-wide PB insertional mutation mapping project at IDM, Fudan University. PMID:19958505

The present situation of prophylactic vaccination in Japan for travel abroad.

PubMed

Nakano, Takashi

2008-11-01

The current situation of vaccination in Japan is reviewed from a viewpoint of overseas travelers. Vaccinations before travel to developing countries, where the risk of infection is high, are recommended for two reasons: "individual protection" and "prevention of communicable disease importation". However, there are problems in Japan; some vaccines available commonly in foreign nations are not approved in Japan and the vaccination schedule is not convenient for travelers. Vaccination is sometimes needed also for travel to Europe and North America. This is because certain vaccinations are required for entering school or studying abroad. In Japan, there is no regulation which recommends vaccination as an entrance requirement. Compared with other nations, Japanese children receive fewer vaccines routinely. On the other hand, there are different features from other industrialized nations, such as routine childhood BCG vaccination and immunization against Japanese encephalitis in Japan. Compared with foreign nations, awareness as regards "travel medicine" is lower in Japan. Recognizing this situation will lead to improvement of vaccination of travelers.

Vaccine production, distribution, access and uptake

PubMed Central

Smith, Jon; Lipsitch, Marc; Almond, Jeffrey W.

2011-01-01

Making human vaccines available on a global scale requires the use of complex production methods, meticulous quality control and reliable distribution channels that ensure the products are potent and effective at their point of use. The technologies involved in manufacturing different types of vaccines may strongly influence vaccine cost, ease of industrial scale-up, stability and ultimately world-wide availability. Manufacturing complexity is compounded by the need for different formulations for different countries and age groups. Reliable vaccine production in appropriate quantities and at affordable prices is the cornerstone of developing global vaccination policies. However, ensuring optimal access and uptake also requires strong partnerships between private manufacturers, regulatory authorities and national and international public health services. For vaccines whose supplies are limited, either due to rapidly emerging diseases or longer-term mismatch of supply and demand, prioritizing target groups can increase vaccine impact. Focusing on influenza vaccines as an example that well illustrates many of the relevant points, this article considers current production, distribution, access and other factors that ultimately impact on vaccine uptake and population-level effectiveness. PMID:21664680

Case study for a vaccine against leishmaniasis.

PubMed

Alvar, Jorge; Croft, Simon L; Kaye, Paul; Khamesipour, Ali; Sundar, Shyam; Reed, Steven G

2013-04-18

Leishmaniasis in many ways offers a unique vaccine case study. Two reasons for this are that leishmaniasis is a disease complex caused by several different species of parasite that are highly related, thus raising the possibility of developing a single vaccine to protect against multiple diseases. Another reason is the demonstration that a leishmaniasis vaccine may be used therapeutically as well as prophylactically. Although there is no registered human leishmaniasis vaccine today, immunization approaches using live or killed organisms, as well as defined vaccine candidates, have demonstrated at least some degree of efficacy in humans to prevent and to treat some forms of leishmaniasis, and there is a vigorous pipeline of candidates in development. Current approaches include using individual or combined antigens of the parasite or of salivary gland extract of the parasites' insect vector, administered with or without formulation in adjuvant. Animal data obtained with several vaccine candidates are promising and some have been or will be entered into clinical testing in the near future. There is sufficient scientific and epidemiological justification to continue to invest in the development of vaccines against leishmaniasis. Copyright © 2012 Elsevier Ltd. All rights reserved.

A bibliographical surveys of large-scale systems

NASA Technical Reports Server (NTRS)

Corliss, W. R.

1970-01-01

A limited, partly annotated bibliography was prepared on the subject of large-scale system control. Approximately 400 references are divided into thirteen application areas, such as large societal systems and large communication systems. A first-author index is provided.

Dengvaxia sensitizes seronegatives to vaccine enhanced disease regardless of age.

PubMed

Halstead, Scott B

2017-11-07

During a large scale clinical efficacy trial of the Sanofipasteur live-attenuated tetravalent dengue vaccine (Dengvaxia), features of hospitalized disease accompanying dengue infections in placebo recipients were closely similar to those in vaccinated children. However, the age specific hospitalization curves for these two populations differed. The curve for children vaccinated at ages 2-16 years closely resembled the 1981 age specific hospitalization rate curve for Cuban children infected with DENV 2 who were sensitized by a prior DENV 1 infection. The corresponding age specific hospitalization curve for placebos experiencing heterotypic secondary dengue infections peaked at age, 9-11 years. These differing epidemiological features support the conclusion that antibody dependent enhanced (ADE) dengue disease occurred in seronegatives who were sensitized by vaccine. As hospitalizations continue to occur in all age groups Dengvaxia consumers should be warned that sensitized vaccinated seronegatives will experience enhanced dengue disease into the forseeable future. Copyright © 2017 Elsevier Ltd. All rights reserved.

Delivering vaccines to the people who need them most.

PubMed

Barocchi, Michèle Anne; Rappuoli, Rino

2015-06-19

Thanks to the Global Alliance for Vaccines and Immunization (GAVI), the Vaccine Fund and the Bill & Melinda Gates Foundation, the global health community has made enormous progress in providing already existing vaccines to developing countries. However, there still exists a gap to develop vaccines for which there is no market in the Western world, owing to low economic incentives for the private sector to justify the investments necessary for vaccine development. In many cases, industry has the technologies, but lacks the impetus to direct resources to develop these vaccine products. The present emergency with the Ebola vaccine provides us an excellent example where a vaccine was feasible several years ago, but the global health community waited for a humanitarian disaster to direct efforts and resources to develop this vaccine. In the beginning of 2015, the first large-scale trials of two experimental vaccines against Ebola virus disease have begun in West Africa. During the past few years, several institutions have dedicated efforts to the development of vaccines against diseases present only in low-income countries. These include the International Vaccine Institute, the Novartis Vaccines Institute for Global Health, the Hilleman Institute, the Sabin Vaccine Institute and the Infectious Disease Research Institute. Nevertheless, solving this problem requires a more significant global effort than that currently invested. These efforts include a clear policy, global coordination of funds dedicated to the development of neglected disease and an agreement on regulatory strategies and incentives for the private sector. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Cost Effectiveness of a Shingles Vaccine Booster for Currently Vaccinated Adults in the U.S.

PubMed

Le, Phuc; Rothberg, Michael B

2017-12-01

The Advisory Committee on Immunization Practices recommends a single dose of the live attenuated herpes zoster vaccine in people aged ≥60 years. Because vaccine-induced protection decreases to zero after 10 years, many vaccinated people will soon be subject to an increased risk of the disease. The study objective was to determine the cost effectiveness of a herpes zoster vaccine booster and its optimal timing among immunocompetent adults first vaccinated at aged ≥60 years. A Markov model was built to follow vaccinated individuals for a lifetime. From the societal perspective, costs and quality-adjusted life years were compared between no booster versus booster options. A booster was given any time between 1 and 20 years after the first dose, and for those who had the first dose at different ages: 60, 70, and 80 years. Because people entered the model already vaccinated, costs and side effects of the first dose were not included. The booster was assumed to have the same efficacy and waning rate as the initial vaccination. Model inputs were based on published literature. A cost effectiveness threshold of $100,000/quality-adjusted life year was used. The analysis was conducted in 2016. Cost effectiveness of a booster varied by age and time since vaccination. The booster cost <$100,000/quality-adjusted life year if given >5 years after the initial dose, but was most cost effective at around 10 years. The finding was robust to wide variations in model inputs. Under current assumptions, a booster dose of herpes zoster vaccine would be cost effective for all vaccinated people 10 years after initial vaccination. Copyright © 2017 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Systematic Review and Meta-analysis of Indirect Protection Afforded by Vaccinating Children Against Seasonal Influenza: Implications for Policy.

PubMed

Yin, J Kevin; Heywood, Anita E; Georgousakis, Melina; King, Catherine; Chiu, Clayton; Isaacs, David; Macartney, Kristine K

2017-09-01

Universal childhood vaccination is a potential solution to reduce seasonal influenza burden. We reviewed systematically the literature on "herd"/indirect protection from vaccinating children aged 6 months to 17 years against influenza. Of 30 studies included, 14 (including 1 cluster randomized controlled trial [cRCT]) used live attenuated influenza vaccine, 11 (7 cRCTs) used inactivated influenza vaccine, and 5 (1 cRCT) compared both vaccine types. Twenty of 30 studies reported statistically significant indirect protection effectiveness (IPE) with point estimates ranging from 4% to 66%. Meta-regression suggests that studies with high quality and/or sufficiently large sample size are more likely to report significant IPE. In meta-analyses of 6 cRCTs with full randomization (rated as moderate quality overall), significant IPE was found in 1 cRCT in closely connected communities where school-aged children were vaccinated: 60% (95% confidence interval [CI], 41%-72%; I2 = 0%; N = 2326) against laboratory-confirmed influenza, and 3 household cRCTs in which preschool-aged children were vaccinated: 22% (95% CI, 1%-38%; I2 = 0%; N = 1903) against acute respiratory infections or influenza-like illness. Significant IPE was also reported in a large-scale cRCT (N = 8510) that was not fully randomized, and 3 ecological studies (N > 10000) of moderate quality including 36% reduction in influenza-related mortality among the elderly in a Japanese school-based program. Data on IPE in other settings are heterogeneous and lacked power to draw a firm conclusion. The available evidence suggests that influenza vaccination of children confers indirect protection in some but not all settings. Robust, large-scaled studies are required to better quantify the indirect protection from vaccinating children for different settings/endpoints. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e

Plant-made vaccine antigens and biopharmaceuticals

PubMed Central

Daniell, Henry; Singh, Nameirakpam D.; Mason, Hugh; Streatfield, Stephen J.

2009-01-01

Plant cells are ideal bioreactors for the production and oral delivery of vaccines and biopharmaceuticals, eliminating the need for expensive fermentation, purification, cold storage, transportation and sterile delivery. Plant-made vaccines have been developed for two decades but none has advanced beyond Phase I. However, two plant-made biopharmaceuticals are now advancing through Phase II and Phase III human clinical trials. In this review, we evaluate the advantages and disadvantages of different plant expression systems (stable nuclear and chloroplast or transient viral) and their current limitations or challenges. We provide suggestions for advancing this valuable concept for clinical applications and conclude that greater research emphasis is needed on large scale production, purification, functional characterization, oral delivery and preclinical evaluation. PMID:19836291

Evolution of scaling emergence in large-scale spatial epidemic spreading.

PubMed

Wang, Lin; Li, Xiang; Zhang, Yi-Qing; Zhang, Yan; Zhang, Kan

2011-01-01

Zipf's law and Heaps' law are two representatives of the scaling concepts, which play a significant role in the study of complexity science. The coexistence of the Zipf's law and the Heaps' law motivates different understandings on the dependence between these two scalings, which has still hardly been clarified. In this article, we observe an evolution process of the scalings: the Zipf's law and the Heaps' law are naturally shaped to coexist at the initial time, while the crossover comes with the emergence of their inconsistency at the larger time before reaching a stable state, where the Heaps' law still exists with the disappearance of strict Zipf's law. Such findings are illustrated with a scenario of large-scale spatial epidemic spreading, and the empirical results of pandemic disease support a universal analysis of the relation between the two laws regardless of the biological details of disease. Employing the United States domestic air transportation and demographic data to construct a metapopulation model for simulating the pandemic spread at the U.S. country level, we uncover that the broad heterogeneity of the infrastructure plays a key role in the evolution of scaling emergence. The analyses of large-scale spatial epidemic spreading help understand the temporal evolution of scalings, indicating the coexistence of the Zipf's law and the Heaps' law depends on the collective dynamics of epidemic processes, and the heterogeneity of epidemic spread indicates the significance of performing targeted containment strategies at the early time of a pandemic disease.

Serologic response in eight alpacas vaccinated by extralabel use of a large animal rabies vaccine during a public health response to a rabid alpaca in South Carolina.

PubMed

Wallace, Ryan M; Niezgoda, Michael; Waggoner, Emily A; Blanton, Jesse Dean; Radcliffe, Rachel A

2016-09-15

CASE DESCRIPTION A female alpaca, kept at pasture with 12 other female alpacas, 2 crias, and 5 goats, was evaluated because of clinical signs of aggression. CLINICAL FINDINGS The clinical signs of aggression progressed to include biting at other animals as well as disorientation. Three days later, the alpaca was euthanized because of suspicion of rabies virus infection. TREATMENT AND OUTCOME No physical injuries were found at necropsy. Brain tissue specimens were confirmed positive for rabies on the basis of direct fluorescent antibody test results. Molecular typing identified the rabies virus variant as one that is enzootic in raccoons. The farm was placed under quarantine, restricting movement of animals on and off the property for 6 months. To prevent further rabies cases, 14 alpacas (12 adults and 2 crias) were vaccinated by extralabel use of a large animal rabies vaccine. Of the 14 vaccinated alpacas, 8 had paired serum samples obtained immediately before and 21 days after vaccination; all 8 alpacas had adequate serum antirabies antibody production in response to rabies vaccination. As a result of an adequate serologic response, the quarantine was reduced to 3 months. In the year after the index rabies case, no other animals on the farm developed rabies. CLINICAL RELEVANCE Extralabel use of rabies vaccines in camelids was used in the face of a public health investigation. This report provides an example of handling of a rabies case for future public health investigations, which will undoubtedly need to develop ad-hoc rabies vaccination recommendations on the basis of the unique characteristics of the event.

Efficacy of a live attenuated Edwardsiella ictaluri oral vaccine in channel and hybrid catfish

USDA-ARS?s Scientific Manuscript database

This study evaluated the efficacy of an oral live-attenuated Edwardsiella ictaluri vaccine against enteric septicemia of catfish (ESC) in channel and hybrid catfish. The vaccine was delivered orally by feeding fish a diet coated with an attenuated E. ictaluri isolate at four doses to deliver betwee...

Moon-based Earth Observation for Large Scale Geoscience Phenomena

NASA Astrophysics Data System (ADS)

Guo, Huadong; Liu, Guang; Ding, Yixing

2016-07-01

The capability of Earth observation for large-global-scale natural phenomena needs to be improved and new observing platform are expected. We have studied the concept of Moon as an Earth observation in these years. Comparing with manmade satellite platform, Moon-based Earth observation can obtain multi-spherical, full-band, active and passive information,which is of following advantages: large observation range, variable view angle, long-term continuous observation, extra-long life cycle, with the characteristics of longevity ,consistency, integrity, stability and uniqueness. Moon-based Earth observation is suitable for monitoring the large scale geoscience phenomena including large scale atmosphere change, large scale ocean change,large scale land surface dynamic change,solid earth dynamic change,etc. For the purpose of establishing a Moon-based Earth observation platform, we already have a plan to study the five aspects as follows: mechanism and models of moon-based observing earth sciences macroscopic phenomena; sensors' parameters optimization and methods of moon-based Earth observation; site selection and environment of moon-based Earth observation; Moon-based Earth observation platform; and Moon-based Earth observation fundamental scientific framework.

Large-Scale Structure and Hyperuniformity of Amorphous Ices

NASA Astrophysics Data System (ADS)

Martelli, Fausto; Torquato, Salvatore; Giovambattista, Nicolas; Car, Roberto

2017-09-01

We investigate the large-scale structure of amorphous ices and transitions between their different forms by quantifying their large-scale density fluctuations. Specifically, we simulate the isothermal compression of low-density amorphous ice (LDA) and hexagonal ice to produce high-density amorphous ice (HDA). Both HDA and LDA are nearly hyperuniform; i.e., they are characterized by an anomalous suppression of large-scale density fluctuations. By contrast, in correspondence with the nonequilibrium phase transitions to HDA, the presence of structural heterogeneities strongly suppresses the hyperuniformity and the system becomes hyposurficial (devoid of "surface-area fluctuations"). Our investigation challenges the largely accepted "frozen-liquid" picture, which views glasses as structurally arrested liquids. Beyond implications for water, our findings enrich our understanding of pressure-induced structural transformations in glasses.

Developments in rabies vaccines.

PubMed

Hicks, D J; Fooks, A R; Johnson, N

2012-09-01

The development of vaccines that prevent rabies has a long and distinguished history, with the earliest preceding modern understanding of viruses and the mechanisms of immune protection against disease. The correct application of inactivated tissue culture-derived vaccines is highly effective at preventing the development of rabies, and very few failures are recorded. Furthermore, oral and parenteral vaccination is possible for wildlife, companion animals and livestock, again using inactivated tissue culture-derived virus. However, rabies remains endemic in many regions of the world and causes thousands of human deaths annually. There also remain no means of prophylaxis for rabies once the virus enters the central nervous system (CNS). One reason for this is the poor immune response within the CNS to infection with rabies virus (RABV). New approaches to vaccination using modified rabies viruses that express components of the innate immune system are being applied to this problem. Preliminary reports suggest that direct inoculation of such viruses could trigger an effective anti-viral response and prevent a fatal outcome from RABV infection. © 2012 Crown copyright. Clinical and Experimental Immunology © 2012 British Society for Immunology.

Scale-up of recombinant Opc protein production in Escherichia coli for a meningococcal vaccine.

PubMed

Pérez, Raúl Espinosa; Lasa, Alexis Musacchio; Rodríguez, Ricardo Silva; Menéndez, Evelin Caballero; Suárez, José García; Balaguer, Héctor Díaz

2006-12-15

Opc is an outer membrane protein from Neisseria meningitidis present in meningococcal vaccine preparations. The opc gene, codifying for this protein, was cloned in to Escherichia coli and the Opc protein was expressed under the control of a tryptophan promoter. The recombinant strain was grown in batch cultures. Opc was expressed as inclusion bodies at about 32% of the total cellular protein. We examined the scale-up culture conditions for the production of the recombinant Opc. The scale-up process was performed from 1.5 l to 50 l culture, using first, the constant power per unit of volume (P/V) as main scaling criteria, and then the oxygen mass transfer coefficient (K(L)a) scaling criteria to adjust the optimal aeration conditions. A final productivity of 52 mgl(-1)h(-1) was obtained at the 50l culture scale compared with the 49 mgl(-1)h(-1) productivity at 1.5l laboratory scale.

The delicate balance in genetically engineering live vaccines

PubMed Central

Galen, James E.; Curtiss, Roy

2014-01-01

Contemporary vaccine development relies less on empirical methods of vaccine construction, and now employs a powerful array of precise engineering strategies to construct immunogenic live vaccines. In this review, we will survey various engineering techniques used to create attenuated vaccines, with an emphasis on recent advances and insights. We will further explore the adaptation of attenuated strains to create multivalent vaccine platforms for immunization against multiple unrelated pathogens. These carrier vaccines are engineered to deliver sufficient levels of protective antigens to appropriate lymphoid inductive sites to elicit both carrier-specific and foreign antigen-specific immunity. Although many of these technologies were originally developed for use in Salmonella vaccines, application of the essential logic of these approaches will be extended to development of other enteric vaccines where possible. A central theme driving our discussion will stress that the ultimate success of an engineered vaccine rests on achieving the proper balance between attenuation and immunogenicity. Achieving this balance will avoid over-activation of inflammatory responses, which results in unacceptable reactogenicity, but will retain sufficient metabolic fitness to enable the live vaccine to reach deep tissue inductive sites and trigger protective immunity. The breadth of examples presented herein will clearly demonstrate that genetic engineering offers the potential for rapidly propelling vaccine development forward into novel applications and therapies which will significantly expand the role of vaccines in public health. PMID:24370705

Health Belief Model Scale for Human Papilloma Virus and its Vaccination: Adaptation and Psychometric Testing.

PubMed

Guvenc, Gulten; Seven, Memnun; Akyuz, Aygul

2016-06-01

To adapt and psychometrically test the Health Belief Model Scale for Human Papilloma Virus (HPV) and Its Vaccination (HBMS-HPVV) for use in a Turkish population and to assess the Human Papilloma Virus Knowledge score (HPV-KS) among female college students. Instrument adaptation and psychometric testing study. The sample consisted of 302 nursing students at a nursing school in Turkey between April and May 2013. Questionnaire-based data were collected from the participants. Information regarding HBMS-HPVV and HPV knowledge and descriptive characteristic of participants was collected using translated HBMS-HPVV and HPV-KS. Test-retest reliability was evaluated and Cronbach α was used to assess internal consistency reliability, and exploratory factor analysis was used to assess construct validity of the HBMS-HPVV. The scale consists of 4 subscales that measure 4 constructs of the Health Belief Model covering the perceived susceptibility and severity of HPV and the benefits and barriers. The final 14-item scale had satisfactory validity and internal consistency. Cronbach α values for the 4 subscales ranged from 0.71 to 0.78. Total HPV-KS ranged from 0 to 8 (scale range, 0-10; 3.80 ± 2.12). The HBMS-HPVV is a valid and reliable instrument for measuring young Turkish women's beliefs and attitudes about HPV and its vaccination. Copyright © 2015 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Large Scale Cross Drive Correlation Of Digital Media

DTIC Science & Technology

2016-03-01

NAVAL POSTGRADUATE SCHOOL MONTEREY, CALIFORNIA THESIS LARGE SCALE CROSS-DRIVE CORRELATION OF DIGITAL MEDIA by Joseph Van Bruaene March 2016 Thesis Co...CROSS-DRIVE CORRELATION OF DIGITAL MEDIA 5. FUNDING NUMBERS 6. AUTHOR(S) Joseph Van Bruaene 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Naval...the ability to make large scale cross-drive correlations among a large corpus of digital media becomes increasingly important. We propose a

Fact and fiction in tuberculosis vaccine research: 10 years later.

PubMed

Kaufmann, Stefan H E

2011-08-01

Tuberculosis is one of the most deadly infectious diseases. The situation is worsening because of co-infection with HIV and increased occurrence of drug resistance. Although the BCG vaccine has been in use for 90 years, protection is insufficient; new vaccine candidates are therefore needed. 12 potential vaccines have gone into clinical trials. Ten are aimed at prevention of tuberculosis and, of these, seven are subunit vaccines either as adjuvanted or viral-vectored antigens. These vaccines would be boosters of BCG-prime vaccination. Three vaccines are recombinant BCG constructs-possible replacements for BCG. Additional vaccine candidates will enter clinical trials in the near future, including postexposure vaccines for individuals with latent infection. In the long term, vaccines that prevent or eradicate infection with Mycobacterium tuberculosis would be the best possible option. Improved knowledge of immunology, molecular microbiology, cell biology, biomics, and biotechnology has paved the way towards an effective and safe vaccine against tuberculosis. The pipeline of new vaccine candidates from preclinical to clinical testing could be accelerated by development of biomarkers that can predict the clinical outcome of tuberculosis. Copyright © 2011 Elsevier Ltd. All rights reserved.

The large-scale distribution of galaxies

NASA Technical Reports Server (NTRS)

Geller, Margaret J.

1989-01-01

The spatial distribution of galaxies in the universe is characterized on the basis of the six completed strips of the Harvard-Smithsonian Center for Astrophysics redshift-survey extension. The design of the survey is briefly reviewed, and the results are presented graphically. Vast low-density voids similar to the void in Bootes are found, almost completely surrounded by thin sheets of galaxies. Also discussed are the implications of the results for the survey sampling problem, the two-point correlation function of the galaxy distribution, the possibility of detecting large-scale coherent flows, theoretical models of large-scale structure, and the identification of groups and clusters of galaxies.

A large-scale clinical validation of an integrated monitoring system in the emergency department.

PubMed

Clifton, David A; Wong, David; Clifton, Lei; Wilson, Sarah; Way, Rob; Pullinger, Richard; Tarassenko, Lionel

2013-07-01

We consider an integrated patient monitoring system, combining electronic patient records with high-rate acquisition of patient physiological data. There remain many challenges in increasing the robustness of "e-health" applications to a level at which they are clinically useful, particularly in the use of automated algorithms used to detect and cope with artifact in data contained within the electronic patient record, and in analyzing and communicating the resultant data for reporting to clinicians. There is a consequential "plague of pilots," in which engineering prototype systems do not enter into clinical use. This paper describes an approach in which, for the first time, the Emergency Department (ED) of a major research hospital has adopted such systems for use during a large clinical trial. We describe the disadvantages of existing evaluation metrics when applied to such large trials, and propose a solution suitable for large-scale validation. We demonstrate that machine learning technologies embedded within healthcare information systems can provide clinical benefit, with the potential to improve patient outcomes in the busy environment of a major ED and other high-dependence areas of patient care.

Development of the PANVAC-VF vaccine for pancreatic cancer.

PubMed

Petrulio, Christian A; Kaufman, Howard L

2006-02-01

PANVAC-VF is a vaccine regimen composed of a priming dose of recombinant vaccinia virus and booster doses of recombinant fowlpox virus expressing carcinoembryonic antigen, mucin-1 and a triad of costimulatory molecules (TRICOM), which include B7.1, intercellular adhesion molecule-1 and leukocyte function-associated antigen-3. Vaccination is administered by subcutaneous injection followed by 4 days of local recombinant adjuvant granulocyte-macrophage colony-stimulating factor at the vaccination site. The vaccine has been developed for patients with advanced pancreatic cancer and has now entered a randomized Phase III clinical trial. This review will describe the background of recombinant poxvirus technology for tumor vaccine development, detail the key preclinical studies supporting the regimen, review the clinical trials supporting the current Phase III study, and highlight the key challenges and future obstacles to successful implementation of PANVAC-VF for pancreatic cancer.

Large-scale environments of narrow-line Seyfert 1 galaxies

NASA Astrophysics Data System (ADS)

Järvelä, E.; Lähteenmäki, A.; Lietzen, H.; Poudel, A.; Heinämäki, P.; Einasto, M.

2017-09-01

Studying large-scale environments of narrow-line Seyfert 1 (NLS1) galaxies gives a new perspective on their properties, particularly their radio loudness. The large-scale environment is believed to have an impact on the evolution and intrinsic properties of galaxies, however, NLS1 sources have not been studied in this context before. We have a large and diverse sample of 1341 NLS1 galaxies and three separate environment data sets constructed using Sloan Digital Sky Survey. We use various statistical methods to investigate how the properties of NLS1 galaxies are connected to the large-scale environment, and compare the large-scale environments of NLS1 galaxies with other active galactic nuclei (AGN) classes, for example, other jetted AGN and broad-line Seyfert 1 (BLS1) galaxies, to study how they are related. NLS1 galaxies reside in less dense environments than any of the comparison samples, thus confirming their young age. The average large-scale environment density and environmental distribution of NLS1 sources is clearly different compared to BLS1 galaxies, thus it is improbable that they could be the parent population of NLS1 galaxies and unified by orientation. Within the NLS1 class there is a trend of increasing radio loudness with increasing large-scale environment density, indicating that the large-scale environment affects their intrinsic properties. Our results suggest that the NLS1 class of sources is not homogeneous, and furthermore, that a considerable fraction of them are misclassified. We further support a published proposal to replace the traditional classification to radio-loud, and radio-quiet or radio-silent sources with a division into jetted and non-jetted sources.

Double inflation - A possible resolution of the large-scale structure problem

NASA Technical Reports Server (NTRS)

Turner, Michael S.; Villumsen, Jens V.; Vittorio, Nicola; Silk, Joseph; Juszkiewicz, Roman

1987-01-01

A model is presented for the large-scale structure of the universe in which two successive inflationary phases resulted in large small-scale and small large-scale density fluctuations. This bimodal density fluctuation spectrum in an Omega = 1 universe dominated by hot dark matter leads to large-scale structure of the galaxy distribution that is consistent with recent observational results. In particular, large, nearly empty voids and significant large-scale peculiar velocity fields are produced over scales of about 100 Mpc, while the small-scale structure over less than about 10 Mpc resembles that in a low-density universe, as observed. Detailed analytical calculations and numerical simulations are given of the spatial and velocity correlations.

Measuring the Large-scale Solar Magnetic Field

NASA Astrophysics Data System (ADS)

Hoeksema, J. T.; Scherrer, P. H.; Peterson, E.; Svalgaard, L.

2017-12-01

The Sun's large-scale magnetic field is important for determining global structure of the corona and for quantifying the evolution of the polar field, which is sometimes used for predicting the strength of the next solar cycle. Having confidence in the determination of the large-scale magnetic field of the Sun is difficult because the field is often near the detection limit, various observing methods all measure something a little different, and various systematic effects can be very important. We compare resolved and unresolved observations of the large-scale magnetic field from the Wilcox Solar Observatory, Heliseismic and Magnetic Imager (HMI), Michelson Doppler Imager (MDI), and Solis. Cross comparison does not enable us to establish an absolute calibration, but it does allow us to discover and compensate for instrument problems, such as the sensitivity decrease seen in the WSO measurements in late 2016 and early 2017.

Issues in pediatric vaccine-preventable diseases in low- to middle-income countries

PubMed Central

Dbaibo, Ghassan; Tatochenko, Vladimir; Wutzler, Peter

2016-01-01

ABSTRACT The highest burden of pediatric vaccine-preventable disease is found in developing nations where resource constraints pose the greatest challenge, impacting disease diagnosis and surveillance as well as the implementation of large scale vaccination programmes. In November 2012, a Working Group Meeting convened in Casablanca to describe and discuss the status with respect to 8 vaccine-preventable diseases (pertussis, pneumococcal disease, measles-mumps-rubella-varicella (MMRV), rotavirus and meningococcal meningitis) to identify and consider ways of overcoming obstacles to pediatric vaccine implementation. Experts from Europe, Russia, the Commonwealth of Independent States, the Middle East, Africa and South East Asia participated in the meeting. A range of region-specific needs and barriers to uptake were discussed. The aim of this article is to provide a summary of the ongoing status with respect to pediatric vaccine preventable disease in the countries represented, and the experts' opinions and recommendations with respect to pediatric vaccine implementation. PMID:27322436

Lessons from HIV-1 vaccine efficacy trials.

PubMed

Excler, Jean-Louis; Michael, Nelson L

2016-11-01

Only four HIV-1 vaccine concepts have been tested in six efficacy trials with no product licensed to date. Several scientific and programmatic lessons can be learned from these studies generating new hypotheses and guiding future steps. RV144 [ALVAC-HIV (canarypox vector) and AIDSVAX B/E (bivalent gp120 HIV-1 subtype B and CRF01_AE)] remains the only efficacy trial that demonstrated a modest vaccine efficacy, which led to the identification of immune correlates of risk. Progress on subtype-specific, ALVAC (canarypox vector) and gp120 vaccine prime-boost approaches has been slow, but we are finally close to the launch of an efficacy study in Africa in 2016. The quest of a globally effective HIV-1 vaccine has led to the development of new approaches. Efficacy studies of combinations of Adenovirus type 26 (Ad26)/Modified Vaccinia Ankara (MVA)/gp140 vaccines with mosaic designs will enter efficacy studies mid-2017 and cytomegalovirus (CMV)-vectored vaccines begin Phase I studies at the same time. Future HIV-1 vaccine efficacy trials face practical challenges as effective nonvaccine prevention programs are projected to decrease HIV-1 incidence. An HIV-1 vaccine is urgently needed. Increased industry involvement, mobilization of resources, expansion of a robust pipeline of new concepts, and robust preclinical challenge studies will be essential to accelerate efficacy testing of next generation HIV-1 vaccine candidates.

Plastid Molecular Pharming I. Production of Oral Vaccines via Plastid Transformation.

PubMed

Berecz, Bernadett; Zelenyánszki, Helga; Pólya, Sára; Tamás-Nyitrai, Cecília; Oszvald, Mária

2017-01-01

Vaccines produced in plants have opened up new opportunities in vaccination. Among the various categories of vaccines, the recombinant vaccine is generally regarded as the most economical and safest type because it cannot cause disease and does not require large-scale cultivation of pathogens. Due to the low cost of their cultivation, plants may represent viable alternative platforms for producing subunit vaccines. Genetic engineering of plastids is the innovation of the last three decades and has numerous benefits when compared to nuclear transformation. Due to the high level of expression, oral vaccines produced in transplastomic plants do not have to be purified as they can be consumed raw, which, therefore, reduces the cost of preparation, transportation and handling of the vaccines. Oral vaccination also excludes the risk of other infections or contaminations, while compartmentation of the plant cell provides an excellent encapsulation to the antigen within the plastid. Herein we review the main biotechnological and immunological aspects of the progress achieved in the field of plastid derived edible vaccines during the last decade. As there is a public debate against genetically modified crops, the advantages and limitations of oral vaccines are also discussed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Influence of oral polio vaccines on performance of the monovalent and pentavalent rotavirus vaccines.

PubMed

Patel, Manish; Steele, A Duncan; Parashar, Umesh D

2012-04-27

In recent years, two live, oral rotavirus vaccines have been successfully tested in developing and industrialized countries, and both vaccines are now recommended by the World Health Organization for all children worldwide. Both immunogenicity and efficacy of these rotavirus vaccines has been lower in developing compared to industrialized settings. We reviewed the data on the effect of trivalent OPV on the immunogenicity and efficacy of two rotavirus vaccines currently recommended by the WHO. While rotavirus vaccines have not affected immune responses to OPV, in general, the immune responses (i.e., antibody levels) to rotavirus vaccination were lower when rotavirus vaccines were co-administered with OPV. Limited data suggests that the interference is greater after the first dose of OPV, presumably because the first dose is associated with greatest intestinal replication of vaccine polio virus strains, and this interference is largely overcome with subsequent rotavirus vaccine doses. Despite the lower immunogenicity, one large efficacy study in middle income Latin American countries showed no decrease in protective efficacy of rotavirus vaccine in infants receiving concurrent OPV. While these data are encouraging and support simultaneous administration of rotavirus vaccines and OPV, additional evidence should be gathered as rotavirus vaccines are used more widely in developing country settings, where OPV is routinely used, rather than inactivated polio vaccine. Published by Elsevier Ltd.

Spectral fingerprints of large-scale neuronal interactions.

PubMed

Siegel, Markus; Donner, Tobias H; Engel, Andreas K

2012-01-11

Cognition results from interactions among functionally specialized but widely distributed brain regions; however, neuroscience has so far largely focused on characterizing the function of individual brain regions and neurons therein. Here we discuss recent studies that have instead investigated the interactions between brain regions during cognitive processes by assessing correlations between neuronal oscillations in different regions of the primate cerebral cortex. These studies have opened a new window onto the large-scale circuit mechanisms underlying sensorimotor decision-making and top-down attention. We propose that frequency-specific neuronal correlations in large-scale cortical networks may be 'fingerprints' of canonical neuronal computations underlying cognitive processes.

Polio vaccines: WHO position paper, January 2014--recommendations.

PubMed

2014-07-16

This article presents the World Health Organizations (WHO) evidence and recommendations for the use of polio vaccination from the WHO position paper on polio vaccines - January 2014 recently published in the Weekly Epidemiological Record [1]. This position paper summarizes the WHO position on the introduction of at least one dose of inactivated polio vaccine (IPV) into routine immunization schedules as a strategy to mitigate the potential risk of re-emergence of type 2 polio following the withdrawal of Sabin type 2 strains from oral polio vaccine (OPV). The current document replaces the position paper on the use of polio vaccines published in 2010 [2]. Footnotes to this paper provide a number of core references. In accordance with its mandate to provide guidance to Member States on health policy matters, WHO issues a series of regularly updated position papers on vaccines and combinations of vaccines against diseases that have an international public health impact. These papers are concerned primarily with the use of vaccines in large-scale immunization programmes; they summarize essential background information on diseases and vaccines, and conclude with WHO's current position on the use of vaccines in the global context. This paper reflects the recommendations of WHO's Strategic Advisory Group of Experts (SAGE) on immunization. These recommendations were discussed by SAGE at its November 2013 meeting. Evidence presented at the meeting can be accessed at http://www.who.int/immunization/sage/previous/en/index.html. Copyright © 2014 World Health Organization. Published by Elsevier Ltd.. All rights reserved.

A unified large/small-scale dynamo in helical turbulence

NASA Astrophysics Data System (ADS)

Bhat, Pallavi; Subramanian, Kandaswamy; Brandenburg, Axel

2016-09-01

We use high resolution direct numerical simulations (DNS) to show that helical turbulence can generate significant large-scale fields even in the presence of strong small-scale dynamo action. During the kinematic stage, the unified large/small-scale dynamo grows fields with a shape-invariant eigenfunction, with most power peaked at small scales or large k, as in Subramanian & Brandenburg. Nevertheless, the large-scale field can be clearly detected as an excess power at small k in the negatively polarized component of the energy spectrum for a forcing with positively polarized waves. Its strength overline{B}, relative to the total rms field Brms, decreases with increasing magnetic Reynolds number, ReM. However, as the Lorentz force becomes important, the field generated by the unified dynamo orders itself by saturating on successively larger scales. The magnetic integral scale for the positively polarized waves, characterizing the small-scale field, increases significantly from the kinematic stage to saturation. This implies that the small-scale field becomes as coherent as possible for a given forcing scale, which averts the ReM-dependent quenching of overline{B}/B_rms. These results are obtained for 10243 DNS with magnetic Prandtl numbers of PrM = 0.1 and 10. For PrM = 0.1, overline{B}/B_rms grows from about 0.04 to about 0.4 at saturation, aided in the final stages by helicity dissipation. For PrM = 10, overline{B}/B_rms grows from much less than 0.01 to values of the order the 0.2. Our results confirm that there is a unified large/small-scale dynamo in helical turbulence.

Modulation of Small-scale Turbulence Structure by Large-scale Motions in the Absence of Direct Energy Transfer.

NASA Astrophysics Data System (ADS)

Brasseur, James G.; Juneja, Anurag

1996-11-01

Previous DNS studies indicate that small-scale structure can be directly altered through ``distant'' dynamical interactions by energetic forcing of the large scales. To remove the possibility of stimulating energy transfer between the large- and small-scale motions in these long-range interactions, we here perturb the large scale structure without altering its energy content by suddenly altering only the phases of large-scale Fourier modes. Scale-dependent changes in turbulence structure appear as a non zero difference field between two simulations from identical initial conditions of isotropic decaying turbulence, one perturbed and one unperturbed. We find that the large-scale phase perturbations leave the evolution of the energy spectrum virtually unchanged relative to the unperturbed turbulence. The difference field, on the other hand, is strongly affected by the perturbation. Most importantly, the time scale τ characterizing the change in in turbulence structure at spatial scale r shortly after initiating a change in large-scale structure decreases with decreasing turbulence scale r. Thus, structural information is transferred directly from the large- to the smallest-scale motions in the absence of direct energy transfer---a long-range effect which cannot be explained by a linear mechanism such as rapid distortion theory. * Supported by ARO grant DAAL03-92-G-0117

Evolution of Scaling Emergence in Large-Scale Spatial Epidemic Spreading

PubMed Central

Wang, Lin; Li, Xiang; Zhang, Yi-Qing; Zhang, Yan; Zhang, Kan

2011-01-01

Background Zipf's law and Heaps' law are two representatives of the scaling concepts, which play a significant role in the study of complexity science. The coexistence of the Zipf's law and the Heaps' law motivates different understandings on the dependence between these two scalings, which has still hardly been clarified. Methodology/Principal Findings In this article, we observe an evolution process of the scalings: the Zipf's law and the Heaps' law are naturally shaped to coexist at the initial time, while the crossover comes with the emergence of their inconsistency at the larger time before reaching a stable state, where the Heaps' law still exists with the disappearance of strict Zipf's law. Such findings are illustrated with a scenario of large-scale spatial epidemic spreading, and the empirical results of pandemic disease support a universal analysis of the relation between the two laws regardless of the biological details of disease. Employing the United States domestic air transportation and demographic data to construct a metapopulation model for simulating the pandemic spread at the U.S. country level, we uncover that the broad heterogeneity of the infrastructure plays a key role in the evolution of scaling emergence. Conclusions/Significance The analyses of large-scale spatial epidemic spreading help understand the temporal evolution of scalings, indicating the coexistence of the Zipf's law and the Heaps' law depends on the collective dynamics of epidemic processes, and the heterogeneity of epidemic spread indicates the significance of performing targeted containment strategies at the early time of a pandemic disease. PMID:21747932

A Functional Model for Management of Large Scale Assessments.

ERIC Educational Resources Information Center

Banta, Trudy W.; And Others

This functional model for managing large-scale program evaluations was developed and validated in connection with the assessment of Tennessee's Nutrition Education and Training Program. Management of such a large-scale assessment requires the development of a structure for the organization; distribution and recovery of large quantities of…

Current Scientific Issues in Large Scale Atmospheric Dynamics

NASA Technical Reports Server (NTRS)

Miller, T. L. (Compiler)

1986-01-01

Topics in large scale atmospheric dynamics are discussed. Aspects of atmospheric blocking, the influence of transient baroclinic eddies on planetary-scale waves, cyclogenesis, the effects of orography on planetary scale flow, small scale frontal structure, and simulations of gravity waves in frontal zones are discussed.

Inactivated Enterovirus 71 Vaccine Produced by 200-L Scale Serum-Free Microcarrier Bioreactor System Provides Cross-Protective Efficacy in Human SCARB2 Transgenic Mouse.

PubMed

Wu, Chia-Ying; Lin, Yi-Wen; Kuo, Chia-Ho; Liu, Wan-Hsin; Tai, Hsiu-Fen; Pan, Chien-Hung; Chen, Yung-Tsung; Hsiao, Pei-Wen; Chan, Chi-Hsien; Chang, Ching-Chuan; Liu, Chung-Cheng; Chow, Yen-Hung; Chen, Juine-Ruey

2015-01-01

Epidemics and outbreaks caused by infections of several subgenotypes of EV71 and other serotypes of coxsackie A viruses have raised serious public health concerns in the Asia-Pacific region. These concerns highlight the urgent need to develop a scalable manufacturing platform for producing an effective and sufficient quantity of vaccines against deadly enteroviruses. In this report, we present a platform for the large-scale production of a vaccine based on the inactivated EV71(E59-B4) virus. The viruses were produced in Vero cells in a 200 L bioreactor with serum-free medium, and the viral titer reached 10(7) TCID50/mL 10 days after infection when using an MOI of 10(-4). The EV71 virus particles were harvested and purified by sucrose density gradient centrifugation. Fractions containing viral particles were pooled based on ELISA and SDS-PAGE. TEM was used to characterize the morphologies of the viral particles. To evaluate the cross-protective efficacy of the EV71 vaccine, the pooled antigens were combined with squalene-based adjuvant (AddaVAX) or aluminum phosphate (AlPO4) and tested in human SCARB2 transgenic (Tg) mice. The Tg mice immunized with either the AddaVAX- or AlPO4-adjuvanted EV71 vaccine were fully protected from challenges by the subgenotype C2 and C4 viruses, and surviving animals did not show any degree of neurological paralysis symptoms or muscle damage. Vaccine treatments significantly reduced virus antigen presented in the central nervous system of Tg mice and alleviated the virus-associated inflammatory response. These results strongly suggest that this preparation results in an efficacious vaccine and that the microcarrier/bioreactor platform offers a superior alternative to the previously described roller-bottle system.

Intellectual property rights and challenges for development of affordable human papillomavirus, rotavirus and pneumococcal vaccines: Patent landscaping and perspectives of developing country vaccine manufacturers.

PubMed

Chandrasekharan, Subhashini; Amin, Tahir; Kim, Joyce; Furrer, Eliane; Matterson, Anna-Carin; Schwalbe, Nina; Nguyen, Aurélia

2015-11-17

The success of Gavi, the Vaccine Alliance depends on the vaccine markets providing appropriate, affordable vaccines at sufficient and reliable quantities. Gavi's current supplier base for new and underutilized vaccines, such as the human papillomavirus (HPV), rotavirus, and the pneumococcal conjugate vaccine is very small. There is growing concern that following globalization of laws on intellectual property rights (IPRs) through trade agreements, IPRs are impeding new manufacturers from entering the market with competing vaccines. This article examines the extent to which IPRs, specifically patents, can create such obstacles, in particular for developing country vaccine manufacturers (DCVMs). Through building patent landscapes in Brazil, China, and India and interviews with manufacturers and experts in the field, we found intense patenting activity for the HPV and pneumococcal vaccines that could potentially delay the entry of new manufacturers. Increased transparency around patenting of vaccine technologies, stricter patentability criteria suited for local development needs and strengthening of IPRs management capabilities where relevant, may help reduce impediments to market entry for new manufacturers and ensure a competitive supplier base for quality vaccines at sustainably low prices. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Differential Epidemiology of Salmonella Typhi and Paratyphi A in Kathmandu, Nepal: A Matched Case Control Investigation in a Highly Endemic Enteric Fever Setting

PubMed Central

Tran Vu Thieu, Nga; Dongol, Sabina; Le Thi Phuong, Tu; Voong Vinh, Phat; Arjyal, Amit; Martin, Laura B.; Rondini, Simona; Farrar, Jeremy J.; Dolecek, Christiane; Basnyat, Buddha; Baker, Stephen

2013-01-01

Background Enteric fever, a systemic infection caused by the bacteria Salmonella Typhi and Salmonella Paratyphi A, is endemic in Kathmandu, Nepal. Previous work identified proximity to poor quality water sources as a community-level risk for infection. Here, we sought to examine individual-level risk factors related to hygiene and sanitation to improve our understanding of the epidemiology of enteric fever in this setting. Methodology and principal findings A matched case-control analysis was performed through enrollment of 103 blood culture positive enteric fever patients and 294 afebrile community-based age and gender-matched controls. A detailed questionnaire was administered to both cases and controls and the association between enteric fever infection and potential exposures were examined through conditional logistic regression. Several behavioral practices were identified as protective against infection with enteric fever, including water storage and hygienic habits. Additionally, we found that exposures related to poor water and socioeconomic status are more influential in the risk of infection with S. Typhi, whereas food consumption habits and migration play more of a role in risk of S. Paratyphi A infection. Conclusions and significance Our work suggests that S. Typhi and S. Paratyphi A follow different routes of infection in this highly endemic setting and that sustained exposure to both serovars probably leads to the development of passive immunity. In the absence of a polyvalent vaccine against S. Typhi and S. Paratyphi A, we advocate better systems for water treatment and storage, improvements in the quality of street food, and vaccination with currently available S. Typhi vaccines. PMID:23991240

Condition Monitoring of Large-Scale Facilities

NASA Technical Reports Server (NTRS)

Hall, David L.

1999-01-01

This document provides a summary of the research conducted for the NASA Ames Research Center under grant NAG2-1182 (Condition-Based Monitoring of Large-Scale Facilities). The information includes copies of view graphs presented at NASA Ames in the final Workshop (held during December of 1998), as well as a copy of a technical report provided to the COTR (Dr. Anne Patterson-Hine) subsequent to the workshop. The material describes the experimental design, collection of data, and analysis results associated with monitoring the health of large-scale facilities. In addition to this material, a copy of the Pennsylvania State University Applied Research Laboratory data fusion visual programming tool kit was also provided to NASA Ames researchers.

WHO position on the use of fractional doses - June 2017, addendum to vaccines and vaccination against yellow fever WHO: Position paper - June 2013.

PubMed

World Health Organization

2017-10-13

This article presents the World Health Organization's (WHO) recommendations on the use of fractional doses of yellow fever vaccines excerpted from the "Yellow fever vaccine: WHO position on the use of fractional doses - June 2017, Addendum to Vaccines and vaccination against yellow fever WHO: Position Paper - June 2013″, published in the Weekly Epidemiological Record [1,2]. This addendum to the 2013 position paper pertains specifically to use of fractional dose YF (fYF) vaccination (fractional dose yellow fever vaccination refers to administration of a reduced volume of vaccine dose, which has been reconstituted as usual per manufacturer recommendations) in the context of YF vaccine supply shortages beyond the capacity of the global stockpile. The current WHO position on the use of yellow fever (YF) vaccine is set out in the 2013 WHO position paper on vaccines and vaccination against YF and those recommendations are unchanged. Footnotes to this paper provide a number of core references including references to grading tables that assess the quality of the scientific evidence, and to the evidence-to-recommendation table. In accordance with its mandate to provide guidance to Member States on health policy matters, WHO issues a series of regularly updated position papers on vaccines and combinations of vaccines against diseases that have an international public health impact. These papers are concerned primarily with the use of vaccines in large-scale immunization programmes; they summarize essential background information on diseases and vaccines, and conclude with WHO's current position on the use of vaccines in the global context. Recommendations on the use of Yellow Fever vaccines were discussed by SAGE in October 2016; evidence presented at these meetings can be accessed at: www.who.int/immunization/sage/meetings/2016/October/presentations_background_docs/en/. Copyright © 2017. Published by Elsevier Ltd.

Seismic safety in conducting large-scale blasts

NASA Astrophysics Data System (ADS)

Mashukov, I. V.; Chaplygin, V. V.; Domanov, V. P.; Semin, A. A.; Klimkin, M. A.

2017-09-01

In mining enterprises to prepare hard rocks for excavation a drilling and blasting method is used. With the approach of mining operations to settlements the negative effect of large-scale blasts increases. To assess the level of seismic impact of large-scale blasts the scientific staff of Siberian State Industrial University carried out expertise for coal mines and iron ore enterprises. Determination of the magnitude of surface seismic vibrations caused by mass explosions was performed using seismic receivers, an analog-digital converter with recording on a laptop. The registration results of surface seismic vibrations during production of more than 280 large-scale blasts at 17 mining enterprises in 22 settlements are presented. The maximum velocity values of the Earth’s surface vibrations are determined. The safety evaluation of seismic effect was carried out according to the permissible value of vibration velocity. For cases with exceedance of permissible values recommendations were developed to reduce the level of seismic impact.

Humoral Immunity to Primary Smallpox Vaccination: Impact of Childhood versus Adult Immunization on Vaccinia Vector Vaccine Development in Military Populations.

PubMed

Slike, Bonnie M; Creegan, Matthew; Marovich, Mary; Ngauy, Viseth

2017-01-01

Modified Vaccinia virus has been shown to be a safe and immunogenic vector platform for delivery of HIV vaccines. Use of this vector is of particular importance to the military, with the implementation of a large scale smallpox vaccination campaign in 2002 in active duty and key civilian personnel in response to potential bioterrorist activities. Humoral immunity to smallpox vaccination was previously shown to be long lasting (up to 75 years) and protective. However, using vaccinia-vectored vaccine delivery for other diseases on a background of anti-vector antibodies (i.e. pre-existing immunity) may limit their use as a vaccine platform, especially in the military. In this pilot study, we examined the durability of vaccinia antibody responses in adult primary vaccinees in a healthy military population using a standard ELISA assay and a novel dendritic cell neutralization assay. We found binding and neutralizing antibody (NAb) responses to vaccinia waned after 5-10 years in a group of 475 active duty military, born after 1972, who were vaccinated as adults with Dryvax®. These responses decreased from a geometric mean titer (GMT) of 250 to baseline (<20) after 10-20 years post vaccination. This contrasted with a comparator group of adults, ages 35-49, who were vaccinated with Dryvax® as children. In the childhood vaccinees, titers persisted for >30 years with a GMT of 210 (range 112-3234). This data suggests limited durability of antibody responses in adult vaccinees compared to those vaccinated in childhood and further that adult vaccinia recipients may benefit similarly from receipt of a vaccinia based vaccine as those who are vaccinia naïve. Our findings may have implications for the smallpox vaccination schedule and support the ongoing development of this promising viral vector in a military vaccination program.

Humoral Immunity to Primary Smallpox Vaccination: Impact of Childhood versus Adult Immunization on Vaccinia Vector Vaccine Development in Military Populations

PubMed Central

Slike, Bonnie M.; Creegan, Matthew

2017-01-01

Modified Vaccinia virus has been shown to be a safe and immunogenic vector platform for delivery of HIV vaccines. Use of this vector is of particular importance to the military, with the implementation of a large scale smallpox vaccination campaign in 2002 in active duty and key civilian personnel in response to potential bioterrorist activities. Humoral immunity to smallpox vaccination was previously shown to be long lasting (up to 75 years) and protective. However, using vaccinia-vectored vaccine delivery for other diseases on a background of anti-vector antibodies (i.e. pre-existing immunity) may limit their use as a vaccine platform, especially in the military. In this pilot study, we examined the durability of vaccinia antibody responses in adult primary vaccinees in a healthy military population using a standard ELISA assay and a novel dendritic cell neutralization assay. We found binding and neutralizing antibody (NAb) responses to vaccinia waned after 5–10 years in a group of 475 active duty military, born after 1972, who were vaccinated as adults with Dryvax®. These responses decreased from a geometric mean titer (GMT) of 250 to baseline (<20) after 10–20 years post vaccination. This contrasted with a comparator group of adults, ages 35–49, who were vaccinated with Dryvax® as children. In the childhood vaccinees, titers persisted for >30 years with a GMT of 210 (range 112–3234). This data suggests limited durability of antibody responses in adult vaccinees compared to those vaccinated in childhood and further that adult vaccinia recipients may benefit similarly from receipt of a vaccinia based vaccine as those who are vaccinia naïve. Our findings may have implications for the smallpox vaccination schedule and support the ongoing development of this promising viral vector in a military vaccination program. PMID:28046039

Potential for geophysical experiments in large scale tests.

USGS Publications Warehouse

Dieterich, J.H.

1981-01-01

Potential research applications for large-specimen geophysical experiments include measurements of scale dependence of physical parameters and examination of interactions with heterogeneities, especially flaws such as cracks. In addition, increased specimen size provides opportunities for improved recording resolution and greater control of experimental variables. Large-scale experiments using a special purpose low stress (100MPa).-Author

Idiotype vaccines for lymphoma: Potential factors predicting the induction of immune responses

PubMed Central

Inoges, Susana; de Cerio, Ascension Lopez-Diaz; Villanueva, Helena; Pastor, Fernando; Soria, Elena; Bendandi, Maurizio

2011-01-01

Over the last two decades, lymphoma idiotype vaccines have been the first human cancer vaccines to show striking evidence of biological and clinical efficacy on the one hand, as well as clinical benefit on the other. More recently, however, three large-scale, independent, randomized clinical trials on idiotypic vaccination have failed to achieve their main clinical endpoints for reasons likely to depend more on flaws in each clinical trial’s study design than on each vaccination strategy per se. Independently of these considerations, a major hurdle for the development of this substantially innocuous and yet potentially very effective type of treatment has been the fact that, even to date, no factors ascertainable before vaccination have been prospectively singled out as predictors of subsequently vaccine-induced, idiotype-specific immune as well as clinical responses. The aim of this review article is precisely to analyze what has been and what could be done in this respect in order to give a greater chance of success to future trials aimed at regulatory approval of idiotype vaccines. PMID:21773074

Polio vaccines: WHO position paper, March 2016-recommendations.

PubMed

World Health Organization

2017-03-01

This article presents the World Health Organization's (WHO) recommendations on the use of polio vaccine excerpted from the WHO position paper on polio vaccines - March 2016, published in the Weekly Epidemiological Record [1]. This position paper on polio vaccines replaces the 2014 WHO position paper [2]. The position paper summarizes the WHO position on the introduction of at least one dose of inactivated polio vaccine (IPV) into routine immunization schedules as a strategy to mitigate the potential risk of re-emergence of type 2 polio following the withdrawal of Sabin type 2 strains from oral polio vaccine (OPV) [3]. Footnotes to this paper provide a number of core references including references to grading tables that assess the quality of the scientific evidence, and to the evidence-to-recommendation table. In accordance with its mandate to provide guidance to Member States on health policy matters, WHO issues a series of regularly updated position papers on vaccines and combinations of vaccines against diseases that have an international public health impact. These papers are concerned primarily with the use of vaccines in large-scale immunization programmes; they summarize essential background information on diseases and vaccines, and conclude with WHO's current position on the use of vaccines in the global context. This position paper reflects the global switch from trivalent to bivalent OPV which took place in April 2016. Recommendations on the use of polio vaccines have been discussed on multiple occasions by SAGE, most recently in October 2016; evidence presented at these meetings can be accessed at: http://www.who.int/immunization/sage/previous/en/index.html. Copyright © 2016 Elsevier Ltd. All rights reserved.

An effective strategy for influenza vaccination of healthcare workers in Australia: experience at a large health service without a mandatory policy.

PubMed

Heinrich-Morrison, Kristina; McLellan, Sue; McGinnes, Ursula; Carroll, Brendan; Watson, Kerrie; Bass, Pauline; Worth, Leon J; Cheng, Allen C

2015-02-06

Annual influenza vaccination of healthcare workers (HCWs) is recommended in Australia, but uptake in healthcare facilities has historically been low (approximately 50%). The objective of this study was to develop and implement a dedicated campaign to improve uptake of staff influenza annual vaccination at a large Australian health service. A quality improvement program was developed at Alfred Health, a tertiary metropolitan health service spanning 3 campuses. Pre-campaign evaluation was performed by questionnaire in 2013 to plan a multimodal vaccination strategy. Reasons for and against vaccination were captured. A campaign targeting clinical and non-clinical healthcare workers was then implemented between March 31 and July 31 2014. Proportional uptake of influenza vaccination was determined by campus and staff category. Pre-campaign questionnaire responses were received from 1328/6879 HCWs (response rate 20.4%), of which 76% were vaccinated. Common beliefs held by unvaccinated staff included vaccine ineffectiveness (37.1%), that vaccination makes staff unwell (21.0%), or that vaccination is not required because staff are at low risk for acquiring influenza (20.2%). In 2014, 6009/7480 (80.3%) staff were vaccinated, with significant improvement in uptake across all campuses and amongst nursing, medical and allied health staff categories from 2013 to 2014 (p < 0.0001). A non-mandatory multimodal strategy utilising social marketing and a customised staff database was successful in increasing influenza vaccination uptake by all staff categories. The sustainability of dedicated campaigns must be evaluated.

Hepatitis E virus: Current epidemiology and vaccine.

PubMed

Wu, Xing; Chen, Pan; Lin, Huijuan; Hao, Xiaotian; Liang, Zhenglun

2016-10-02

Hepatitis E virus infections have been continuously reported in Indian subcontinent, Africa, southeast and central Asia, posing great health threats to the public, especially to pregnant women. Hecolin® is the only licensed HEV vaccine developed by Xiamen Innovax Biotech Co., Ltd. Extensive characterizations on antigenicity, physicochemical properties, efficacy in clinical trials, and manufacturing capability have made Hecolin® a promising vaccine for HEV control. However, there are many obstacles in large scale application of Hecolin®. Efforts are needed to further evaluate safety and efficacy in HEV risk populations, and to complement HEV standards for quality control. Passing World Health Organization prequalification and licensing outside China are priorities as these are also hindering Hecolin® promotion. Multilateral cooperation among Chinese vaccine manufacturers, Chinese National Regulatory Authorization (NRA) and WHO will expedite the entrance of Hecolin® into international market, so that Hecolin® could play its due role in global hepatitis E control.

Are vaccine strain, type or administration protocol risk factors for canine parvovirus vaccine failure?

PubMed

Altman, K D; Kelman, M; Ward, M P

2017-10-01

Canine parvovirus (CPV) is a highly contagious and worldwide cause of serious and often fatal disease in dogs, despite the widespread availability of vaccines. Which vaccine-related factors are associated with vaccination failure is largely unknown, and there are no reports from Australia. In this study - the first national population-level CPV study of its kind ever conducted - we analysed data on 594 cases of apparent CPV vaccination failure reported from an Australian national surveillance system to determine whether vaccine strain, type or administration protocol are risk factors for vaccination failures. The strain of CPV used in vaccine manufacture was not significantly associated with vaccination failure in clinical practice. The vaccine type (killed versus attenuated vaccine) for puppies diagnosed with CPV was associated with a lower mean age at time of vaccination (P=0.0495). The age at administration of the last CPV vaccination a puppy received prior to presenting with disease was a significant (P=0.0334) risk factor for vaccination failure, irrespective of whether the vaccine was marketed for a 10-week or 12-week or greater vaccination finish protocol. There was also a strong negative correlation between age at last vaccination prior to disease and vaccination failure (P<0.0001): the later a puppy received this last vaccination, the lower the risk of vaccination failure. This supports the hypothesis that the use of final vaccination in puppies at less than 16 weeks of age predisposes to vaccination failure and warrants a final age for vaccination recommendation to be at least 16 weeks for all canine parvovirus vaccines, especially in outbreak situations. The large number of cases identified in this study confirms that CPV vaccination failure is occurring in Australia. Veterinarians should consider CPV as a differential diagnosis in cases with appropriate clinical presentation, regardless of the reported vaccination status of the dog. Copyright © 2017

[The participation of hospital pharmacy services in enteral nutrition].

PubMed

Hidalgo, F J; Bermejo, T; de Juana, P; Delgado, E; García, D

1995-01-01

We present the results of a study done in the departments of hospital pharmacy of our country with the aim of knowing their participation in the use and clinical follow up of patients with enteral nutrition. 293 questionnaires were sent out, and 121 were filled out and returned (41.3%). The responses were classified into three groups, according to the number of hospital beds, considering > or = 1000 (large), 500-1000 (medium), and < or = 500 (small). The data were analyzed by means of a statistical program (R-Sigma Horus). 79% (68) of the small hospitals have a unitary dose drug dispensation system, and the Enteral Nutrition was distributed through this system in 53% (50) of them; only 29% (27) of them have a stock of these preparations on the wards. 93% (14) and 65% (54) of the large and small hospitals respectively, prefer the use of enteral nutrition as opposed to parenteral nutrition. 85% (11) of the large hospitals have protocols for the use of enteral nutrition, this being 62% (10) and 59% (47) in medium and small hospitals. The committees for artificial nutrition are present in 75% of the large hospitals, in addition to which, in 66% of these there is a nutritional support team. A pharmacist from the department of pharmacy participates in both multidisciplinary groups. If it is necessary to manipulate the enteral nutrition preparations, in 30% of the departments of pharmacy of the smaller hospitals, this is centralized, being done by personnel of the department itself; in 59% of them (19) there is a specific area for the elaboration, which is not the case in large hospitals. Drugs are mixed with the enteral nutrition in 25% (1), 12% (1), and 9% (4) of the large, medium and small hospitals respectively. There is great, active participation of the hospital pharmacists in the activities of the multidisciplinary nutritional support systems, although at the present time, the involvement of the departments of pharmacy in the centralization of the manipulation of

Vero cell technology for rapid development of inactivated whole virus vaccines for emerging viral diseases.

PubMed

Barrett, P Noel; Terpening, Sara J; Snow, Doris; Cobb, Ronald R; Kistner, Otfried

2017-09-01

Rapid development and production of vaccines against emerging diseases requires well established, validated, robust technologies to allow industrial scale production and accelerated licensure of products. Areas covered: A versatile Vero cell platform has been developed and utilized to deliver a wide range of candidate and licensed vaccines against emerging viral diseases. This platform builds on the 35 years' experience and safety record with inactivated whole virus vaccines such as polio vaccine. The current platform has been optimized to include a novel double inactivation procedure in order to ensure a highly robust inactivation procedure for novel emerging viruses. The utility of this platform in rapidly developing inactivated whole virus vaccines against pandemic (-like) influenza viruses and other emerging viruses such as West Nile, Chikungunya, Ross River and SARS is reviewed. The potential of the platform for development of vaccines against other emerging viruses such as Zika virus is described. Expert commentary: Use of this platform can substantially accelerate process development and facilitate licensure because of the substantial existing data set available for the cell matrix. However, programs to provide vaccines against emerging diseases must allow alternative clinical development paths to licensure, without the requirement to carry out large scale field efficacy studies.

Homogenization of Large-Scale Movement Models in Ecology

USGS Publications Warehouse

Garlick, M.J.; Powell, J.A.; Hooten, M.B.; McFarlane, L.R.

2011-01-01

A difficulty in using diffusion models to predict large scale animal population dispersal is that individuals move differently based on local information (as opposed to gradients) in differing habitat types. This can be accommodated by using ecological diffusion. However, real environments are often spatially complex, limiting application of a direct approach. Homogenization for partial differential equations has long been applied to Fickian diffusion (in which average individual movement is organized along gradients of habitat and population density). We derive a homogenization procedure for ecological diffusion and apply it to a simple model for chronic wasting disease in mule deer. Homogenization allows us to determine the impact of small scale (10-100 m) habitat variability on large scale (10-100 km) movement. The procedure generates asymptotic equations for solutions on the large scale with parameters defined by small-scale variation. The simplicity of this homogenization procedure is striking when compared to the multi-dimensional homogenization procedure for Fickian diffusion,and the method will be equally straightforward for more complex models. ?? 2010 Society for Mathematical Biology.

The large-scale organization of metabolic networks

NASA Astrophysics Data System (ADS)

Jeong, H.; Tombor, B.; Albert, R.; Oltvai, Z. N.; Barabási, A.-L.

2000-10-01

In a cell or microorganism, the processes that generate mass, energy, information transfer and cell-fate specification are seamlessly integrated through a complex network of cellular constituents and reactions. However, despite the key role of these networks in sustaining cellular functions, their large-scale structure is essentially unknown. Here we present a systematic comparative mathematical analysis of the metabolic networks of 43 organisms representing all three domains of life. We show that, despite significant variation in their individual constituents and pathways, these metabolic networks have the same topological scaling properties and show striking similarities to the inherent organization of complex non-biological systems. This may indicate that metabolic organization is not only identical for all living organisms, but also complies with the design principles of robust and error-tolerant scale-free networks, and may represent a common blueprint for the large-scale organization of interactions among all cellular constituents.

Large-scale weakly supervised object localization via latent category learning.

PubMed

Chong Wang; Kaiqi Huang; Weiqiang Ren; Junge Zhang; Maybank, Steve

2015-04-01

Localizing objects in cluttered backgrounds is challenging under large-scale weakly supervised conditions. Due to the cluttered image condition, objects usually have large ambiguity with backgrounds. Besides, there is also a lack of effective algorithm for large-scale weakly supervised localization in cluttered backgrounds. However, backgrounds contain useful latent information, e.g., the sky in the aeroplane class. If this latent information can be learned, object-background ambiguity can be largely reduced and background can be suppressed effectively. In this paper, we propose the latent category learning (LCL) in large-scale cluttered conditions. LCL is an unsupervised learning method which requires only image-level class labels. First, we use the latent semantic analysis with semantic object representation to learn the latent categories, which represent objects, object parts or backgrounds. Second, to determine which category contains the target object, we propose a category selection strategy by evaluating each category's discrimination. Finally, we propose the online LCL for use in large-scale conditions. Evaluation on the challenging PASCAL Visual Object Class (VOC) 2007 and the large-scale imagenet large-scale visual recognition challenge 2013 detection data sets shows that the method can improve the annotation precision by 10% over previous methods. More importantly, we achieve the detection precision which outperforms previous results by a large margin and can be competitive to the supervised deformable part model 5.0 baseline on both data sets.

Maternal antibody, vaccination and reproductive failure in dogs with parvovirus infection.

PubMed

Gooding, G E; Robinson, W F

1982-12-01

The maternal antibody (MAb) titre to canine parvovirus (CPV) was determined on consecutive serums from 39 puppies in 7 litters. Vaccination with inactivated CPV was performed at a variety of ages and the response of the puppies determined. Transfer of MAb was demonstrated in 71% (5/7) of the litters and persisted for up to 10 weeks in some litters. MAb titres of greater than 20 precluded a vaccination response by puppies. Sixty- one per cent (8/13) of puppies responded to vaccination when the MAb titre was less than 20. However, no anamestic response occurred and in some cases a decrease in antibody titre was observed following a second vaccination. During an outbreak of canine parvovirus enteritis (CPE) in the kennel, 33 puppies developed clinical signs of enteritis. Of these puppies 85% (28) had MAb titres of less than 80 at the onset of clinical signs. Fifty per cent (4/8) of the puppies which responded to vaccination developed CPE, whereas 100% (5/5) of those that did not respond to vaccination developed CPE. The results indicate that MAb may persist for up to 10 weeks and puppies with MAb in the titre range greater than 20 to less than 80 do not respond to vaccination but are still susceptible to infection. It is also apparent that a significant minority of puppies with MAb less than 20 do not respond to vaccination. An examination of the breeding records of the kennel for the 7 year period 1973-1981 demonstrated a sudden decrease in reproductive efficiency during and subsequent to 1978. This coincided with the recognition of cases of CPV infection in the kennel. It is suggested that further investigation is required into the possible role of CPV in reproductive failure.

Yeast Surface-Displayed H5N1 Avian Influenza Vaccines

PubMed Central

Lei, Han; Jin, Sha; Karlsson, Erik; Schultz-Cherry, Stacey

2016-01-01

Highly pathogenic H5N1 avian influenza viruses pose a pandemic threat to human health. A rapid vaccine production against fast outbreak is desired. We report, herein, a paradigm-shift influenza vaccine technology by presenting H5N1 hemagglutinin (HA) to the surface of yeast. We demonstrated, for the first time, that the HA surface-presented yeast can be used as influenza vaccines to elicit both humoral and cell-mediated immunity in mice. The HI titer of antisera reached up to 128 in vaccinated mice. A high level of H5N1 HA-specific IgG1 and IgG2a antibody production was detected after boost immunization. Furthermore, we demonstrated that the yeast surface-displayed HA preserves its antigenic sites. It preferentially binds to both avian- and human-type receptors. In addition, the vaccine exhibited high cross-reactivity to both homologous and heterologous H5N1 viruses. A high level production of anti-HA antibodies was detected in the mice five months after vaccination. Finally, our animal experimental results indicated that the yeast vaccine offered complete protection of mice from lethal H5N1 virus challenge. No severe side effect of yeast vaccines was noted in animal studies. This new technology allows for rapid and large-scale production of influenza vaccines for prepandemic preparation. PMID:28078309

Development of a recombinant toxin fragment vaccine for Clostridium difficile infection.

PubMed

Karczewski, Jerzy; Zorman, Julie; Wang, Su; Miezeiewski, Matthew; Xie, Jinfu; Soring, Keri; Petrescu, Ioan; Rogers, Irene; Thiriot, David S; Cook, James C; Chamberlin, Mihaela; Xoconostle, Rachel F; Nahas, Debbie D; Joyce, Joseph G; Bodmer, Jean-Luc; Heinrichs, Jon H; Secore, Susan

2014-05-19

Clostridium difficile infection (CDI) is the major cause of antibiotic-associated diarrhea and pseudomembranous colitis, a disease associated with significant morbidity and mortality. The disease is mostly of nosocomial origin, with elderly patients undergoing anti-microbial therapy being particularly at risk. C. difficile produces two large toxins: Toxin A (TcdA) and Toxin B (TcdB). The two toxins act synergistically to damage and impair the colonic epithelium, and are primarily responsible for the pathogenesis associated with CDI. The feasibility of toxin-based vaccination against C. difficile is being vigorously investigated. A vaccine based on formaldehyde-inactivated Toxin A and Toxin B (toxoids) was reported to be safe and immunogenic in healthy volunteers and is now undergoing evaluation in clinical efficacy trials. In order to eliminate cytotoxic effects, a chemical inactivation step must be included in the manufacturing process of this toxin-based vaccine. In addition, the large-scale production of highly toxic antigens could be a challenging and costly process. Vaccines based on non-toxic fragments of genetically engineered versions of the toxins alleviate most of these limitations. We have evaluated a vaccine assembled from two recombinant fragments of TcdB and explored their potential as components of a novel experimental vaccine against CDI. Golden Syrian hamsters vaccinated with recombinant fragments of TcdB combined with full length TcdA (Toxoid A) developed high titer IgG responses and potent neutralizing antibody titers. We also show here that the recombinant vaccine protected animals against lethal challenge with C. difficile spores, with efficacy equivalent to the toxoid vaccine. The development of a two-segment recombinant vaccine could provide several advantages over toxoid TcdA/TcdB such as improvements in manufacturability. Copyright © 2014 Elsevier Ltd. All rights reserved.

Parasite Carbohydrate Vaccines.

PubMed

Jaurigue, Jonnel A; Seeberger, Peter H

2017-01-01

Vaccination is an efficient means of combating infectious disease burden globally. However, routine vaccines for the world's major human parasitic diseases do not yet exist. Vaccines based on carbohydrate antigens are a viable option for parasite vaccine development, given the proven success of carbohydrate vaccines to combat bacterial infections. We will review the key components of carbohydrate vaccines that have remained largely consistent since their inception, and the success of bacterial carbohydrate vaccines. We will then explore the latest developments for both traditional and non-traditional carbohydrate vaccine approaches for three of the world's major protozoan parasitic diseases-malaria, toxoplasmosis, and leishmaniasis. The traditional prophylactic carbohydrate vaccine strategy is being explored for malaria. However, given that parasite disease biology is complex and often arises from host immune responses to parasite antigens, carbohydrate vaccines against deleterious immune responses in host-parasite interactions are also being explored. In particular, the highly abundant glycosylphosphatidylinositol molecules specific for Plasmodium, Toxoplasma , and Leishmania spp. are considered exploitable antigens for this non-traditional vaccine approach. Discussion will revolve around the application of these protozoan carbohydrate antigens for vaccines currently in preclinical development.

Parasite Carbohydrate Vaccines

PubMed Central

Jaurigue, Jonnel A.; Seeberger, Peter H.

2017-01-01

Vaccination is an efficient means of combating infectious disease burden globally. However, routine vaccines for the world's major human parasitic diseases do not yet exist. Vaccines based on carbohydrate antigens are a viable option for parasite vaccine development, given the proven success of carbohydrate vaccines to combat bacterial infections. We will review the key components of carbohydrate vaccines that have remained largely consistent since their inception, and the success of bacterial carbohydrate vaccines. We will then explore the latest developments for both traditional and non-traditional carbohydrate vaccine approaches for three of the world's major protozoan parasitic diseases—malaria, toxoplasmosis, and leishmaniasis. The traditional prophylactic carbohydrate vaccine strategy is being explored for malaria. However, given that parasite disease biology is complex and often arises from host immune responses to parasite antigens, carbohydrate vaccines against deleterious immune responses in host-parasite interactions are also being explored. In particular, the highly abundant glycosylphosphatidylinositol molecules specific for Plasmodium, Toxoplasma, and Leishmania spp. are considered exploitable antigens for this non-traditional vaccine approach. Discussion will revolve around the application of these protozoan carbohydrate antigens for vaccines currently in preclinical development. PMID:28660174

Vaccination-induced distemper in kinkajous.

PubMed

Kazacos, K R; Thacker, H L; Shivaprasad, H L; Burger, P P

1981-12-01

Following vaccination for distemper, using a modified live-virus vaccine developed for dogs, 2 young kinkajous (Potos flavus) developed diarrhea, then central nervous system disease. Clinical signs included myoclonus, head trembling, loss of muscular coordination, and convulsions. One kinkajou gradually recovered; the other seemed to recover, then relapsed and was euthanatized. Microscopic lesions included those of interstitial pneumonia and enteritis and multifocal lymphocytic inflammation, gliosis, spongiosis, and swollen and degenerating axons in the cerebral, cerebellar, and brain stem white matter. Similar lesions were found at all caudally, as exemplified by complete destruction of the dorsal funiculi and dorsal horns of the gray matter of the upper sacral cord segments. Eosinophilic intranuclear inclusions were seen histologically in the glia in the spinal cord, midbrain, and cerebellum, and were confirmed as canine distemper viral inclusions by the fluorescent antibody method. It was concluded that modified live canine distemper virus vaccines should be used with caution or not at all in kinkajous.

Large-scale structure of randomly jammed spheres

NASA Astrophysics Data System (ADS)

Ikeda, Atsushi; Berthier, Ludovic; Parisi, Giorgio

2017-05-01

We numerically analyze the density field of three-dimensional randomly jammed packings of monodisperse soft frictionless spherical particles, paying special attention to fluctuations occurring at large length scales. We study in detail the two-point static structure factor at low wave vectors in Fourier space. We also analyze the nature of the density field in real space by studying the large-distance behavior of the two-point pair correlation function, of density fluctuations in subsystems of increasing sizes, and of the direct correlation function. We show that such real space analysis can be greatly improved by introducing a coarse-grained density field to disentangle genuine large-scale correlations from purely local effects. Our results confirm that both Fourier and real space signatures of vanishing density fluctuations at large scale are absent, indicating that randomly jammed packings are not hyperuniform. In addition, we establish that the pair correlation function displays a surprisingly complex structure at large distances, which is however not compatible with the long-range negative correlation of hyperuniform systems but fully compatible with an analytic form for the structure factor. This implies that the direct correlation function is short ranged, as we also demonstrate directly. Our results reveal that density fluctuations in jammed packings do not follow the behavior expected for random hyperuniform materials, but display instead a more complex behavior.

Genetic diversity of G1P[8] rotavirus VP7 and VP8* antigens in Finland over a 20-year period: No evidence for selection pressure by universal mass vaccination with RotaTeq® vaccine.

PubMed

Hemming, Maria; Vesikari, Timo

2013-10-01

Two live-attenuated oral vaccines (Rotarix™ and Rotateq®) against rotavirus gastroenteritis were licensed in 2006 and have been introduced into National Immunization Programs (NIPs) of several countries. Large scale use of rotavirus vaccines might cause antigenic pressure on circulating rotavirus types or lead to selection of new rotaviruses thus decreasing vaccine efficacy. We examined the nucleotide and amino acid sequences of the surface proteins VP7 and VP4 (cleaved to VP8(*) and VP5(*)) of a total of 108 G1P[8] rotavirus strains collected over a 20-year period from 1992, including the years 2006-2009 when rotavirus vaccine (mainly Rotarix™) was available, and the years 2009-2012 after implementation of RotaTeq® vaccine into the NIP of Finland. In G1 VP7 no changes at amino acid level were observed. In VP8(*) periodical fluctuation of the sublineage over the study period was found with multiple changes both at nucleotide and amino acid levels. Most amino acid changes were in the dominant antigenic epitopes of VP8(*). A change in VP8(*) sublineage occurred between 2008 and 2009, with a temporal correlation to the use of Rotarix™ up to 30% coverage in the period. In contrast, no antigenic changes in the VP8(*) protein appeared to be correlated to the exclusive use of RotaTeq® vaccine after 2009. Nevertheless, long-term surveillance of antigenic changes in VP4 and also VP7 proteins in wild-type rotavirus strains is warranted in countries with large scale use of the currently licensed live oral rotavirus vaccines. Copyright © 2013 Elsevier B.V. All rights reserved.

An Novel Architecture of Large-scale Communication in IOT

NASA Astrophysics Data System (ADS)

Ma, Wubin; Deng, Su; Huang, Hongbin

2018-03-01

In recent years, many scholars have done a great deal of research on the development of Internet of Things and networked physical systems. However, few people have made the detailed visualization of the large-scale communications architecture in the IOT. In fact, the non-uniform technology between IPv6 and access points has led to a lack of broad principles of large-scale communications architectures. Therefore, this paper presents the Uni-IPv6 Access and Information Exchange Method (UAIEM), a new architecture and algorithm that addresses large-scale communications in the IOT.

Gravitational lenses and large scale structure

NASA Technical Reports Server (NTRS)

Turner, Edwin L.

1987-01-01

Four possible statistical tests of the large scale distribution of cosmic material are described. Each is based on gravitational lensing effects. The current observational status of these tests is also summarized.

Large-Scale 1:1 Computing Initiatives: An Open Access Database

ERIC Educational Resources Information Center

Richardson, Jayson W.; McLeod, Scott; Flora, Kevin; Sauers, Nick J.; Kannan, Sathiamoorthy; Sincar, Mehmet

2013-01-01

This article details the spread and scope of large-scale 1:1 computing initiatives around the world. What follows is a review of the existing literature around 1:1 programs followed by a description of the large-scale 1:1 database. Main findings include: 1) the XO and the Classmate PC dominate large-scale 1:1 initiatives; 2) if professional…

Influenza Vaccinations, Fall 2009: Model School-Located Vaccination Clinics

ERIC Educational Resources Information Center

Herl Jenlink, Carolyn; Kuehnert, Paul; Mazyck, Donna

2010-01-01

The 2009 H1N1 influenza virus presented a major challenge to health departments, schools, and other community partners to effectively vaccinate large numbers of Americans, primarily children. The use of school-located vaccination (SLV) programs to address this challenge led health departments and schools to become creative in developing models for…

Anthrax prevention and treatment: utility of therapy combining antibiotic plus vaccine.

PubMed

Klinman, Dennis M; Yamamoto, Masaki; Tross, Debra; Tomaru, Koji

2009-12-01

The intentional release of anthrax spores in 2001 confirmed this pathogen's ability to cause widespread panic, morbidity and mortality. While individuals exposed to anthrax can be successfully treated with antibiotics, pre-exposure vaccination can reduce susceptibility to infection-induced illness. Concern over the safety and immunogenicity of the licensed US vaccine (Anthrax Vaccine Adsorbed (AVA)) has fueled research into alternatives. Second-generation anthrax vaccines based on purified recombinant protective antigen (rPA) have entered clinical trials. These rPA vaccines induce neutralizing antibodies that prevent illness, but the magnitude and duration of the resultant protective response is modest. Efforts are underway to bolster the immunogenicity of rPA by combining it with adjuvants and other immunostimulatory agents. Third generation vaccines are under development that utilize a wide variety of immunization platforms, antigens, adjuvants, delivery methods and routes of delivery to optimize the induction of a protective immunity. For the foreseeable future, vaccination will rely on first and second generation vaccines co-administered with immune adjuvants. Optimal post-exposure treatment of immunologically naive individuals should include a combination of vaccine plus antibiotic therapy.

Malaria vaccine: WHO position paper, January 2016 - Recommendations.

PubMed

2018-06-14

This article presents the World Health Organization's (WHO) recommendations on the use of malaria vaccine excerpted from the WHO position paper on malaria vaccine published in the Weekly epidemiological Record in January 2016 [1]. The current document is the first WHO position paper on malaria vaccination and focuses primarily on the available evidence concerning the only malaria vaccine having received a positive regulation assessment from the European Medicines Agency (EMA) [2]. The position paper gives consideration to the epidemiological features of the disease and assesses the potential use of the vaccine for public health benefits. Footnotes to this paper provide a number of core references including references to grading tables that assess the quality of the scientific evidence, and to the evidence to recommendation table. In accordance with its mandate to provide guidance to Member States on health policy matters, WHO issues a series of regularly updated position papers on vaccines and combinations of vaccines against diseases that have an international public health impact. These papers are concerned primarily with the use of vaccines in large-scale immunization programmes; they summarize essential background information on diseases and vaccines, and conclude with WHO's current position on the use of vaccines in the global context. This paper reflects the joint recommendation of the WHO's Strategic Advisory Group of Experts (SAGE) on immunization and the Malaria Policy Advisory Committee (MPAC). These recommendations were discussed by SAGE and MPAC at the October 2015 SAGE meeting. Evidence presented at the meeting can be accessed at http://www.who.int/immunization/sage/previous/en/index.html. Copyright © 2016 Elsevier Ltd. All rights reserved.

Development of a therapeutic vaccine for the treatment of cocaine addiction.

PubMed

Fox, B S

1997-12-15

No pharmacotherapies have yet been approved for the treatment of cocaine addiction. One new approach is to block the effects of cocaine with anti-cocaine antibodies induced by a therapeutic cocaine vaccine. A cocaine vaccine has been developed which induces a cocaine-specific antibody response in rodents. The antibody binds to cocaine in the circulation and can be shown to inhibit the ability of cocaine to enter the brain. Furthermore, anti-cocaine antibody can inhibit cocaine self-administration in rats. These data suggest that a cocaine vaccine may be a powerful therapeutic tool. The intent is to immunized motivated patients with the vaccine as part of a comprehensive treatment program. If the patient uses cocaine after being vaccinated, the antibody will inhibit the reinforcing activity of cocaine and decrease the likelihood of relapse.

Oral vaccination through voluntary consumption of the convict grouper Epinephelus septemfasciatus with yeast producing the capsid protein of red-spotted grouper nervous necrosis virus.

PubMed

Cho, Seo Young; Kim, Hyoung Jin; Lan, Nguyen Thi; Han, Hyun-Ja; Lee, Deok-Chan; Hwang, Jee Youn; Kwon, Mun-Gyeong; Kang, Bo Kyu; Han, Sang Yoon; Moon, Hyoungjoon; Kang, Hyun Ah; Kim, Hong-Jin

2017-05-01

Nervous necrosis viruses (NNV) cause serious economic losses in marine fish cultivation. The red-spotted grouper NNV (RGNNV) is the most common species of NNV worldwide. There have been many efforts to develop prophylactic NNV vaccines, and various types of vaccine candidate have been suggested. However, most were designed as injectable vaccines, which are not suitable for large-scale vaccination and cause too much stress to the fish. Oral vaccination through voluntary feeding is an ideal way to provide protective immunity to fish. In the present study, recombinant Saccharomyces cerevisiae producing RGNNV capsid protein was used as oral vaccine. The recombinant yeast was prepared in freeze-dried form after disruption. Convict groupers were divided into three groups, control, and oral and parenteral vaccination groups, each consisting of 700 fishes. The control group received no treatment, the parenteral group received one intraperitoneal injection of RGNNV virus-like particles, and the oral vaccination group consumed feed containing the lysed recombinant yeast; voluntary intake was allowed four times at one-week intervals. Both vaccination groups produced serum RGNNV neutralizing antibody titers of >10 3 (log 2, 9.96), sustained for at least 95days post-immunization. In addition, in response to challenge with RGNNV both groups suffered significantly reduced mortality and had reduced brain RGNNV titers. These results indicate that recombinant yeast-based oral fish vaccines have great potential for large-scale vaccination. Copyright © 2017 Elsevier B.V. All rights reserved.

Progress and challenges in TB vaccine development

PubMed Central

Voss, Gerald; Casimiro, Danilo; Neyrolles, Olivier; Williams, Ann; Kaufmann, Stefan H.E.; McShane, Helen; Hatherill, Mark; Fletcher, Helen A

2018-01-01

The Bacille Calmette Guerin (BCG) vaccine can provide decades of protection against tuberculosis (TB) disease, and although imperfect, BCG is proof that vaccine mediated protection against TB is a possibility. A new TB vaccine is, therefore, an inevitability; the question is how long will it take us to get there? We have made substantial progress in the development of vaccine platforms, in the identification of antigens and of immune correlates of risk of TB disease. We have also standardized animal models to enable head-to-head comparison and selection of candidate TB vaccines for further development.  To extend our understanding of the safety and immunogenicity of TB vaccines we have performed experimental medicine studies to explore route of administration and have begun to develop controlled human infection models. Driven by a desire to reduce the length and cost of human efficacy trials we have applied novel approaches to later stage clinical development, exploring alternative clinical endpoints to prevention of disease outcomes. Here, global leaders in TB vaccine development discuss the progress made and the challenges that remain. What emerges is that, despite scientific progress, few vaccine candidates have entered clinical trials in the last 5 years and few vaccines in clinical trials have progressed to efficacy trials. Crucially, we have undervalued the knowledge gained from our “failed” trials and fostered a culture of risk aversion that has limited new funding for clinical TB vaccine development. The unintended consequence of this abundance of caution is lack of diversity of new TB vaccine candidates and stagnation of the clinical pipeline. We have a variety of new vaccine platform technologies, mycobacterial antigens and animal and human models.  However, we will not encourage progression of vaccine candidates into clinical trials unless we evaluate and embrace risk in pursuit of vaccine development. PMID:29568497

Progress and challenges in TB vaccine development.

PubMed

Voss, Gerald; Casimiro, Danilo; Neyrolles, Olivier; Williams, Ann; Kaufmann, Stefan H E; McShane, Helen; Hatherill, Mark; Fletcher, Helen A

2018-01-01

The Bacille Calmette Guerin (BCG) vaccine can provide decades of protection against tuberculosis (TB) disease, and although imperfect, BCG is proof that vaccine mediated protection against TB is a possibility. A new TB vaccine is, therefore, an inevitability; the question is how long will it take us to get there? We have made substantial progress in the development of vaccine platforms, in the identification of antigens and of immune correlates of risk of TB disease. We have also standardized animal models to enable head-to-head comparison and selection of candidate TB vaccines for further development.  To extend our understanding of the safety and immunogenicity of TB vaccines we have performed experimental medicine studies to explore route of administration and have begun to develop controlled human infection models. Driven by a desire to reduce the length and cost of human efficacy trials we have applied novel approaches to later stage clinical development, exploring alternative clinical endpoints to prevention of disease outcomes. Here, global leaders in TB vaccine development discuss the progress made and the challenges that remain. What emerges is that, despite scientific progress, few vaccine candidates have entered clinical trials in the last 5 years and few vaccines in clinical trials have progressed to efficacy trials. Crucially, we have undervalued the knowledge gained from our "failed" trials and fostered a culture of risk aversion that has limited new funding for clinical TB vaccine development. The unintended consequence of this abundance of caution is lack of diversity of new TB vaccine candidates and stagnation of the clinical pipeline. We have a variety of new vaccine platform technologies, mycobacterial antigens and animal and human models.  However, we will not encourage progression of vaccine candidates into clinical trials unless we evaluate and embrace risk in pursuit of vaccine development.

Spatiotemporal property and predictability of large-scale human mobility

NASA Astrophysics Data System (ADS)

Zhang, Hai-Tao; Zhu, Tao; Fu, Dongfei; Xu, Bowen; Han, Xiao-Pu; Chen, Duxin

2018-04-01

Spatiotemporal characteristics of human mobility emerging from complexity on individual scale have been extensively studied due to the application potential on human behavior prediction and recommendation, and control of epidemic spreading. We collect and investigate a comprehensive data set of human activities on large geographical scales, including both websites browse and mobile towers visit. Numerical results show that the degree of activity decays as a power law, indicating that human behaviors are reminiscent of scale-free random walks known as Lévy flight. More significantly, this study suggests that human activities on large geographical scales have specific non-Markovian characteristics, such as a two-segment power-law distribution of dwelling time and a high possibility for prediction. Furthermore, a scale-free featured mobility model with two essential ingredients, i.e., preferential return and exploration, and a Gaussian distribution assumption on the exploration tendency parameter is proposed, which outperforms existing human mobility models under scenarios of large geographical scales.

[Vaccines against hepatitis A and B in Chile].

PubMed

Valenzuela, M Teresa

2009-06-01

The mode of transmission and epidemiological approach for hepatitis A and B are different. However, both are preventable with vaccines whose efficacy and long lasting protection has been demonstrated. This review describes the secular tendency of both infections in Chile, their risk factors that have contributed to their persistence in the country and the interventions that have been carried out to reduce the disease burden. Although the vaccine for hepatitis B was incorporated to the immunization program in 2005, the vaccine for hepatitis A persists in the list of interventions that must be assumed with priority by the Ministry of Health. If Chilean health authorities pretend to reach the enteric disease indicators of developed countries, they must accelerate the epidemiological transition towards the elimination of hepatitis A.

Wedge measures parallax separations...on large-scale 70-mm

Treesearch

Steven L. Wert; Richard J. Myhre

1967-01-01

A new parallax wedge (range: 1.5 to 2 inches) has been designed for use with large-scaled 70-mm. aerial photographs. The narrow separation of the wedge allows the user to measure small parallax separations that are characteristic of large-scale photographs.

Cervical screening in HPV-vaccinated populations.

PubMed

Canfell, K

2018-06-01

Cervical screening with cytology has been the basis for substantial reductions in cervical cancer incidence and mortality in most high-income countries over the last few decades. More recently, there have been two key, parallel developments which have prompted a major re-consideration of cervical screening. The first is the emergence of evidence on the improved sensitivity of human papillomavirus (HPV) DNA testing compared to cytology, and the second is the large-scale deployment of prophylactic vaccination against HPV. A key challenge to be overcome before HPV screening could be introduced into national cervical screening programs was the specificity of an infection, for detection of precancerous lesions. This has been done in three ways: (1) by considering the appropriate age for starting HPV screening (30 years in unvaccinated populations and 25 years in populations with mature vaccination programs and high vaccine uptake) and the appropriate screening interval; (2) via development of clinical HPV tests, which are (by design) not as sensitive to low viral loads; and (3) by introducing effective triaging for HPV-positive women, which further risk-stratifies women before referral for diagnostic evaluation. This review discusses these major developments and describes how the benefits of HPV screening are being optimized in both unvaccinated and vaccinated populations.

The Sabin live poliovirus vaccination trials in the USSR, 1959.

PubMed Central

Horstmann, D. M.

1991-01-01

Widespread use of the Sabin live attenuated poliovirus vaccine has had tremendous impact on the disease worldwide, virtually eliminating it from a number of countries, including the United States. Early proof of its safety and effectiveness was presented in 1959 by Russian investigators, who had staged massive trials in the USSR, involving millions of children. Their positive results were at first viewed in the United States and elsewhere with some skepticism, but the World Health Organization favored proceeding with large-scale trials, and responded to the claims made by Russian scientists by sending a representative to the USSR to review in detail the design and execution of the vaccine programs and the reliability of their results. The report that followed was a positive endorsement of the findings and contributed to the acceptance of the Sabin vaccine in the United States, where it has been the polio vaccine of choice since the mid-1960s. PMID:1814062

Environmental Enteric Dysfunction in Children.

PubMed

Syed, Sana; Ali, Asad; Duggan, Christopher

2016-07-01

Diarrheal diseases are a major cause of childhood death in resource-poor countries, killing approximately 760,000 children younger than 5 years each year. Although deaths due to diarrhea have declined dramatically, high rates of stunting and malnutrition have persisted. Environmental enteric dysfunction (EED) is a subclinical condition caused by constant fecal-oral contamination with resultant intestinal inflammation and villous blunting. These histological changes were first described in the 1960s, but the clinical effect of EED is only just being recognized in the context of failure of nutritional interventions and oral vaccines in resource-poor countries. We review the existing literature regarding the underlying causes of and potential interventions for EED in children, highlighting the epidemiology, clinical and histologic classification of the entity, and discussing novel biomarkers and possible therapies. Future research priorities are also discussed.

Vaccines Against Malaria

PubMed Central

Ouattara, Amed; Laurens, Matthew B.

2015-01-01

Despite global efforts to control malaria, the illness remains a significant public health threat. Currently, there is no licensed vaccine against malaria, but an efficacious vaccine would represent an important public health tool for successful malaria elimination. Malaria vaccine development continues to be hindered by a poor understanding of antimalarial immunity, a lack of an immune correlate of protection, and the genetic diversity of malaria parasites. Current vaccine development efforts largely target Plasmodium falciparum parasites in the pre-erythrocytic and erythrocytic stages, with some research on transmission-blocking vaccines against asexual stages and vaccines against pregnancy-associated malaria. The leading pre-erythrocytic vaccine candidate is RTS,S, and early results of ongoing Phase 3 testing show overall efficacy of 46% against clinical malaria. The next steps for malaria vaccine development will focus on the design of a product that is efficacious against the highly diverse strains of malaria and the identification of a correlate of protection against disease. PMID:25452593

The global effect of maternal education on complete childhood vaccination: a systematic review and meta-analysis.

PubMed

Forshaw, Jennifer; Gerver, Sarah M; Gill, Moneet; Cooper, Emily; Manikam, Logan; Ward, Helen

2017-12-28

There is an established correlation between maternal education and reduction in childhood mortality. One proposed link is that an increase in maternal education will lead to an increase in health care access and vaccine uptake. Vaccinations are a central preventative child health tool, therefore demonstrating the importance of understanding factors that can improve coverage. This review aims to establish if there is a correlation between increasing maternal education and vaccine uptake and if this varies between continents, setting and time. An electronic database search was conducted using Medline Ovid, Embase and The Cochrane Library using a combination of keywords and appropriate MeSH terms for maternal education and child vaccination. Bibliographies were also hand searched. Data was extracted and entered onto a Microsoft Excel spreadsheet and analysed using STATA 13.0 software. The primary outcome of effect size of maternal education on completion of childhood vaccinations was analysed at different levels. Secondary outcomes were explored using subgroup analyses of differences between continents, rural or urban settings, and dates. The online search yielded 3430 papers, 37 were included in this study. The analysis showed increasing child vaccination uptake with increasing maternal education. Overall, analysis showed that the odds of full childhood vaccination were 2.3 times greater in children whose mother received secondary or higher education when compared to children whose mother had no education. There was large variability in the effect size between the studies included. Improving maternal education is important for increasing childhood vaccination uptake and coverage. Further research is needed in higher income countries. PROSPERO Registration No: CRD42016042409 .

Evaluation of Hepatitis B Vaccination among Lichen Planus Patients.

PubMed

Balighi, K; Daneshpazhooh, M; Nasimi, M; Loloee, S; Asadi, A; Azizpour, A

2016-07-01

Lichen planus (LP) is an idiopathic chronic inflammatory mucocutaneous disease. Many reports in the literature have described hepatitis B vaccine as a predisposing factor for LP. This study was performed to determine the rate of previous vaccination against hepatitis B in LP patients. This was a cross sectional study on LP patients. Diagnosis of LP was confirmed by histological examination. Data were gathered by dermatology residents based on a checklist designed to guide their interview. Blood samples were tested for HBsAB titer, HBsAg, HCV Ab and liver function tests. One hundred & twenty four (124) patients entered the study. Females were 2.72 times more affected. The mean age of patients was 45.63 years (age range; 18-88). Forty-four (35.5%) patients had been vaccinated against hepatitis B. Lichen planus during the first six months of vaccination occurred in only one patient. Our findings bring into question the causative role of HBV vaccine in LP incidence in our population.

Formulation and Stabilization of Francisella tularensis Live Vaccine Strain

PubMed Central

OHTAKE, SATOSHI; MARTIN, RUSSELL A.; SAXENA, ATUL; LECHUGA-BALLESTEROS, DAVID; SANTIAGO, ARACELI E; BARRY, EILEEN M.; TRUONG-LE, VU

2012-01-01

Francisella tularensis live vaccine strain (F. tularensis LVS), a promising vaccine candidate for protection against F. tularensis exposure, is a particularly thermolabile vaccine and difficult to stabilize sufficiently for storage under refrigerated conditions. Our preliminary data show that F. tularensis LVS can be stabilized in the dried state using foam drying, a modified freeze drying method, with sugar-based formulations. The process was conducted under mild drying conditions, which resulted in a good titer retention following processing. The inclusion of osmolytes in the growth media resulted in an acceleration of growth kinetics, although no change in osmotolerance was observed. The optimized F. tularensis formulation, which contained trehalose, gelatin, and Pluronic F68 demonstrated stability for approximately 1.5 weeks at 37°C (i.e., time required for the vaccine to decrease in potency by 1 log10 colony forming unit) and for 12 weeks at 25°C. At refrigerator storage condition (4°C), stabilized F. tularensis LVS vaccine exhibited no activity loss for at least 12 weeks. This stabilization method utilizes conventional freeze dryers and pharmaceutically approved stabilizers, and thus can be readily implemented at many manufacturing sites for large-scale production of stabilized vaccines. The improved heat stability of the F. tularensis LVS could mitigate risks of vaccine potency loss during long-term storage, shipping, and distribution. PMID:21491457

Vaccine approaches to malaria control and elimination: Insights from mathematical models.

PubMed

White, Michael T; Verity, Robert; Churcher, Thomas S; Ghani, Azra C

2015-12-22

A licensed malaria vaccine would provide a valuable new tool for malaria control and elimination efforts. Several candidate vaccines targeting different stages of the malaria parasite's lifecycle are currently under development, with one candidate, RTS,S/AS01 for the prevention of Plasmodium falciparum infection, having recently completed Phase III trials. Predicting the public health impact of a candidate malaria vaccine requires using clinical trial data to estimate the vaccine's efficacy profile--the initial efficacy following vaccination and the pattern of waning of efficacy over time. With an estimated vaccine efficacy profile, the effects of vaccination on malaria transmission can be simulated with the aid of mathematical models. Here, we provide an overview of methods for estimating the vaccine efficacy profiles of pre-erythrocytic vaccines and transmission-blocking vaccines from clinical trial data. In the case of RTS,S/AS01, model estimates from Phase II clinical trial data indicate a bi-phasic exponential profile of efficacy against infection, with efficacy waning rapidly in the first 6 months after vaccination followed by a slower rate of waning over the next 4 years. Transmission-blocking vaccines have yet to be tested in large-scale Phase II or Phase III clinical trials so we review ongoing work investigating how a clinical trial might be designed to ensure that vaccine efficacy can be estimated with sufficient statistical power. Finally, we demonstrate how parameters estimated from clinical trials can be used to predict the impact of vaccination campaigns on malaria using a mathematical model of malaria transmission. Copyright © 2015 Elsevier Ltd. All rights reserved.

Schistosoma egg-induced liver pathology resolution by Sm-p80-based schistosomiasis vaccine in baboons.

PubMed

Le, Loc; Molehin, Adebayo J; Nash, Stewart; Sennoune, Souad R; Ahmad, Gul; Torben, Workineh; Zhang, Weidong; Siddiqui, Afzal A

2018-05-05

Schistosomiasis remains a serious chronic debilitating hepato-intestinal disease. Current control measures based on mass drug administration are inadequate due to sustained re-infection rates, low treatment coverage and emergence of drug resistance. Hence, there is an urgent need for a schistosomiasis vaccine for disease control. In this study, we assessed the anti-pathology efficacy of Schistosoma mansoni large subunit of calpain (Sm-p80)-based vaccine against schistosomiasis caused by infections with Schistosoma mansoni in baboons. We also evaluated the disease transmission-blocking potential of Sm-p80 vaccine. Immunisations with Sm-p80-based vaccine resulted in significant reduction of hepatic egg load in vaccinated baboons (67.7% reduction, p = 0.0032) when compared to the control animals, indicative of reduction in pathology. There was also a significant reduction in sizes of egg-induced granulomas in baboons immunised with Sm-p80 vaccine compared to their control counterparts. Egg hatching rate analysis revealed an overall 85.6% reduction (p = 0.0018) in vaccinated animals compared to the controls, highlighting the potential role of Sm-p80 vaccine in disease transmission. The findings on anti-pathology efficacy and transmission-blocking potential presented in this study have formed the basis for a large-scale double-blinded baboon experiment that is currently underway. Copyright © 2018 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.

Human papillomavirus vaccine policy and delivery in Latin America and the Caribbean.

PubMed

Andrus, Jon Kim; Lewis, Merle J; Goldie, Sue J; García, Patricia J; Winkler, Jennifer L; Ruiz-Matus, Cuauhtémoc; de Quadros, Ciro A

2008-08-19

Cervical cancer caused by human papillomavirus (HPV) is a major preventable public health problem. Two vaccines are now available for primary prevention of HPV infection and their introduction offers new opportunities to enhance comprehensive cervical cancer prevention and control. Currently, HPV vaccine price is a significant barrier to rapid vaccine introduction and access. Therefore, making evidence-based decisions about whether and how to introduce HPV vaccine into the immunization schedule in the countries of Latin America and the Caribbean (LAC) requires a rigorous analysis of several factors. These include: estimates of disease burden, cost-effectiveness, operational feasibility of reaching a population of adolescent females and other key analyses that have been used in recent years to support the introduction of other vaccines, such as rotavirus and pneumococcal conjugate vaccines. Given the large number of public health priorities that are competing for limited public resources, developing and using a sound evidence base is of particular importance for vaccines, like HPV, which are currently available only at prices higher than other vaccines now in use. HPV vaccination provides the opportunity to dramatically improve women's health and partnerships must also be broad-based and effectively coordinated. This can be achieved by developing programs based on the lessons learned from vaccination strategies used to eliminate rubella and neonatal tetanus and for scaling up influenza vaccination in countries of LAC.

Management of large-scale technology

NASA Technical Reports Server (NTRS)

Levine, A.

1985-01-01

Two major themes are addressed in this assessment of the management of large-scale NASA programs: (1) how a high technology agency was a decade marked by a rapid expansion of funds and manpower in the first half and almost as rapid contraction in the second; and (2) how NASA combined central planning and control with decentralized project execution.

Vaccine coverage and adherence to EPI schedules in eight resource poor settings in the MAL-ED cohort study.

PubMed

Hoest, Christel; Seidman, Jessica C; Lee, Gwenyth; Platts-Mills, James A; Ali, Asad; Olortegui, Maribel Paredes; Bessong, Pascal; Chandyo, Ram; Babji, Sudhir; Mohan, Venkata Raghava; Mondal, Dinesh; Mahfuz, Mustafa; Mduma, Estomih R; Nyathi, Emanuel; Abreu, Claudia; Miller, Mark A; Pan, William; Mason, Carl J; Knobler, Stacey L

2017-01-11

Launched in 1974, the Expanded Program on Immunization (EPI) is estimated to prevent two-three million deaths annually from polio, diphtheria, tuberculosis, pertussis, measles, and tetanus. Additional lives could be saved through better understanding what influences adherence to the EPI schedule in specific settings. The Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) study followed cohorts in eight sites in South Asia, Africa, and South America and monitored vaccine receipt over the first two years of life for the children enrolled in the study. Vaccination histories were obtained monthly from vaccination cards, local clinic records and/or caregiver reports. Vaccination histories were compared against the prescribed EPI schedules for each country, and coverage rates were examined in relation to the timing of vaccination. The influence of socioeconomic factors on vaccine timing and coverage was also considered. Coverage rates for EPI vaccines varied between sites and by type of vaccine; overall, coverage was highest in the Nepal and Bangladesh sites and lowest in the Tanzania and Brazil sites. Bacillus Calmette-Guérin coverage was high across all sites, 87-100%, whereas measles vaccination rates ranged widely, 73-100%. Significant delays between the scheduled administration age and actual vaccination date were present in all sites, especially for measles vaccine where less than 40% were administered on schedule. A range of socioeconomic factors were significantly associated with vaccination status in study children but these results were largely site-specific. Our findings highlight the need to improve measles vaccination rates and reduce delayed vaccination to achieve EPI targets related to the establishment of herd immunity and reduction in disease transmission. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Phage display as a promising approach for vaccine development.

PubMed

Aghebati-Maleki, Leili; Bakhshinejad, Babak; Baradaran, Behzad; Motallebnezhad, Morteza; Aghebati-Maleki, Ali; Nickho, Hamid; Yousefi, Mehdi; Majidi, Jafar

2016-09-29

Bacteriophages are specific antagonists to bacterial hosts. These viral entities have attracted growing interest as optimal vaccine delivery vehicles. Phages are well-matched for vaccine design due to being highly stable under harsh environmental conditions, simple and inexpensive large scale production, and potent adjuvant capacities. Phage vaccines have efficient immunostimulatory effects and present a high safety profile because these viruses have made a constant relationship with the mammalian body during a long-standing evolutionary period. The birth of phage display technology has been a turning point in the development of phage-based vaccines. Phage display vaccines are made by expressing multiple copies of an antigen on the surface of immunogenic phage particles, thereby eliciting a powerful and effective immune response. Also, the ability to produce combinatorial peptide libraries with a highly diverse pool of randomized ligands has transformed phage display into a straightforward, versatile and high throughput screening methodology for the identification of potential vaccine candidates against different diseases in particular microbial infections. These libraries can be conveniently screened through an affinity selection-based strategy called biopanning against a wide variety of targets for the selection of mimotopes with high antigenicity and immunogenicity. Also, they can be panned against the antiserum of convalescent individuals to recognize novel peptidomimetics of pathogen-related epitopes. Phage display has represented enormous promise for finding new strategies of vaccine discovery and production and current breakthroughs promise a brilliant future for the development of different phage-based vaccine platforms.

US National Large-scale City Orthoimage Standard Initiative

USGS Publications Warehouse

Zhou, G.; Song, C.; Benjamin, S.; Schickler, W.

2003-01-01

The early procedures and algorithms for National digital orthophoto generation in National Digital Orthophoto Program (NDOP) were based on earlier USGS mapping operations, such as field control, aerotriangulation (derived in the early 1920's), the quarter-quadrangle-centered (3.75 minutes of longitude and latitude in geographic extent), 1:40,000 aerial photographs, and 2.5 D digital elevation models. However, large-scale city orthophotos using early procedures have disclosed many shortcomings, e.g., ghost image, occlusion, shadow. Thus, to provide the technical base (algorithms, procedure) and experience needed for city large-scale digital orthophoto creation is essential for the near future national large-scale digital orthophoto deployment and the revision of the Standards for National Large-scale City Digital Orthophoto in National Digital Orthophoto Program (NDOP). This paper will report our initial research results as follows: (1) High-precision 3D city DSM generation through LIDAR data processing, (2) Spatial objects/features extraction through surface material information and high-accuracy 3D DSM data, (3) 3D city model development, (4) Algorithm development for generation of DTM-based orthophoto, and DBM-based orthophoto, (5) True orthophoto generation by merging DBM-based orthophoto and DTM-based orthophoto, and (6) Automatic mosaic by optimizing and combining imagery from many perspectives.

GENERAL: Epidemic spreading on networks with vaccination

NASA Astrophysics Data System (ADS)

Shi, Hong-Jing; Duan, Zhi-Sheng; Chen, Guan-Rong; Li, Rong

2009-08-01

In this paper, a new susceptible-infected-susceptible (SIS) model on complex networks with imperfect vaccination is proposed. Two types of epidemic spreading patterns (the recovered individuals have or have not immunity) on scale-free networks are discussed. Both theoretical and numerical analyses are presented. The epidemic thresholds related to the vaccination rate, the vaccination-invalid rate and the vaccination success rate on scale-free networks are demonstrated, showing different results from the reported observations. This reveals that whether or not the epidemic can spread over a network under vaccination control is determined not only by the network structure but also by the medicine's effective duration. Moreover, for a given infective rate, the proportion of individuals to vaccinate can be calculated theoretically for the case that the recovered nodes have immunity. Finally, simulated results are presented to show how to control the disease prevalence.

Large-scale structure in superfluid Chaplygin gas cosmology

NASA Astrophysics Data System (ADS)

Yang, Rongjia

2014-03-01

We investigate the growth of the large-scale structure in the superfluid Chaplygin gas (SCG) model. Both linear and nonlinear growth, such as σ8 and the skewness S3, are discussed. We find the growth factor of SCG reduces to the Einstein-de Sitter case at early times while it differs from the cosmological constant model (ΛCDM) case in the large a limit. We also find there will be more stricture growth on large scales in the SCG scenario than in ΛCDM and the variations of σ8 and S3 between SCG and ΛCDM cannot be discriminated.

Utilisation of ISA Reverse Genetics and Large-Scale Random Codon Re-Encoding to Produce Attenuated Strains of Tick-Borne Encephalitis Virus within Days.

PubMed

de Fabritus, Lauriane; Nougairède, Antoine; Aubry, Fabien; Gould, Ernest A; de Lamballerie, Xavier

2016-01-01

Large-scale codon re-encoding is a new method of attenuating RNA viruses. However, the use of infectious clones to generate attenuated viruses has inherent technical problems. We previously developed a bacterium-free reverse genetics protocol, designated ISA, and now combined it with large-scale random codon-re-encoding method to produce attenuated tick-borne encephalitis virus (TBEV), a pathogenic flavivirus which causes febrile illness and encephalitis in humans. We produced wild-type (WT) and two re-encoded TBEVs, containing 273 or 273+284 synonymous mutations in the NS5 and NS5+NS3 coding regions respectively. Both re-encoded viruses were attenuated when compared with WT virus using a laboratory mouse model and the relative level of attenuation increased with the degree of re-encoding. Moreover, all infected animals produced neutralizing antibodies. This novel, rapid and efficient approach to engineering attenuated viruses could potentially expedite the development of safe and effective new-generation live attenuated vaccines.

Childhood vaccination requirements: Lessons from history, Mississippi, and a path forward.

PubMed

Cawkwell, Philip B; Oshinsky, David

2015-10-26

Mississippi consistently leads the United States in childhood vaccination with a greater than 99% measles-mumps-rubella vaccination rate for children entering kindergarten. The story of how this came to pass in a state that lags behind on nearly every other public health measure is pertinent given the recent outbreaks of measles in the United States, especially in pockets of the country where there is strong resistance to vaccination. The fight against compulsory vaccination law is centuries old and the enduring success of Mississippi at repelling challenges to their vaccination requirements is a testament to the public health infrastructure and legal framework established in the state. Herein we trace the anti-vaccination movement from its origins in England up until the present time in the United States and explore how Mississippi has established a model vaccination system. Seminal court cases and legislation are evaluated for their impact. Finally, contemporary battles over vaccination legislation are examined and the feasibility of national-level change is considered. Copyright © 2015 Elsevier Ltd. All rights reserved.

Multiple Vaccinations: Friend or Foe

PubMed Central

Church, Sarah E.; Jensen, Shawn M.; Twitty, Chris; Bahjat, Keith; Hu, Hong-Ming; Urba, Walter J.; Fox, Bernard A.

2013-01-01

Few immunotherapists would accept the concept of a single vaccination inducing a therapeutic anti-cancer immune response in a patient with advanced cancer. But what is the evidence to support the “more-is-better” approach of multiple vaccinations? Since we are unaware of trials comparing the effect of a single vaccine versus multiple vaccinations on patient outcome, we considered that an anti-cancer immune response might provide a surrogate measure of the effectiveness of vaccination strategies. Since few large trials include immunological monitoring, the majority of information is gleaned from smaller trials in which an evaluation of immune responses to vaccine or tumor, before and at one or more times following the first vaccine was performed. In some studies there is convincing evidence that repeated administration of a specific vaccine can augment the immune response to antigens contained in the vaccine. In other settings multiple vaccinations can significantly reduce the immune response to one or more targets. Results from three large adjuvant vaccine studies support the potential detrimental effect of multiple vaccinations as clinical outcomes in the control arms were significantly better than that for treatment groups. Recent research has provided insights into mechanisms that are likely responsible for the reduced responses in the studies noted above, but supporting evidence from clinical specimens is generally lacking. Interpretation of these results is further complicated by the possibility that the dominant immune response may evolve to recognize epitopes not present in the vaccine. Nonetheless, the FDA-approval of the first therapeutic cancer vaccine and recent developments from preclinical models and clinical trials provide a substantial basis for optimism and a critical evaluation of cancer vaccine strategies. PMID:21952289

Collaborative vaccine development: partnering pays.

PubMed

Ramachandra, Rangappa

2008-01-01

Vaccine development, supported by infusions of public and private venture capital, is re-entering a golden age as one of the fastest growing sectors in the life-sciences industry. Demand is driven by great unmet need in underdeveloped countries, increased resistance to current treatments, bioterrorism, and for prevention indications in travelers, pediatric, and adult diseases. Production systems are becoming less reliant on processes such as egg-based manufacturing, while new processes can help to optimize vaccines. Expeditious development hinges on efficient study conduct, which is greatly enhanced through research partnerships with specialized contract research organizations (CROs) that are licensed and knowledgeable in the intricacies of immunology and with the technologic and scientific foundation to support changing timelines and strategies inherent to vaccine development. The CRO often brings a more objective assessment for probability of success and may offer alternative development pathways. Vaccine developers are afforded more flexibility and are free to focus on innovation and internal core competencies. Functions readily outsourced to a competent partner include animal model development, safety and efficacy studies, immunotoxicity and immunogenicity, dose response studies, and stability and potency testing. These functions capitalize on the CRO partner's regulatory and scientific talent and expertise, and reduce infrastructure expenses for the vaccine developer. Successful partnerships result in development efficiencies, elimination or reduced redundancies, and improved time to market. Keys to success include honest communications, transparency, and flexibility.

Geospatial Optimization of Siting Large-Scale Solar Projects

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

Macknick, Jordan; Quinby, Ted; Caulfield, Emmet

2014-03-01

Recent policy and economic conditions have encouraged a renewed interest in developing large-scale solar projects in the U.S. Southwest. However, siting large-scale solar projects is complex. In addition to the quality of the solar resource, solar developers must take into consideration many environmental, social, and economic factors when evaluating a potential site. This report describes a proof-of-concept, Web-based Geographical Information Systems (GIS) tool that evaluates multiple user-defined criteria in an optimization algorithm to inform discussions and decisions regarding the locations of utility-scale solar projects. Existing siting recommendations for large-scale solar projects from governmental and non-governmental organizations are not consistent withmore » each other, are often not transparent in methods, and do not take into consideration the differing priorities of stakeholders. The siting assistance GIS tool we have developed improves upon the existing siting guidelines by being user-driven, transparent, interactive, capable of incorporating multiple criteria, and flexible. This work provides the foundation for a dynamic siting assistance tool that can greatly facilitate siting decisions among multiple stakeholders.« less

Critical Issues in Large-Scale Assessment: A Resource Guide.

ERIC Educational Resources Information Center

Redfield, Doris

The purpose of this document is to provide practical guidance and support for the design, development, and implementation of large-scale assessment systems that are grounded in research and best practice. Information is included about existing large-scale testing efforts, including national testing programs, state testing programs, and…

State of the Art in Large-Scale Soil Moisture Monitoring

NASA Technical Reports Server (NTRS)

Ochsner, Tyson E.; Cosh, Michael Harold; Cuenca, Richard H.; Dorigo, Wouter; Draper, Clara S.; Hagimoto, Yutaka; Kerr, Yan H.; Larson, Kristine M.; Njoku, Eni Gerald; Small, Eric E.;

Designing a VAR2CSA-based vaccine to prevent placental malaria.

PubMed

Fried, Michal; Duffy, Patrick E

2015-12-22

Placental malaria (PM) due to Plasmodium falciparum is a major cause of maternal, fetal and infant mortality, but the mechanisms of pathogenesis and protective immunity are relatively well-understood for this condition, providing a path for vaccine development. P. falciparum parasites bind to chondroitin sulfate A (CSA) to sequester in the placenta, and women become resistant over 1-2 pregnancies as they acquire antibodies that block adhesion to CSA. The protein VAR2CSA, a member of the PfEMP1 variant surface antigen family, mediates parasite adhesion to CSA, and is the leading target for a vaccine to prevent PM. Obstacles to PM vaccine development include the large size (∼ 350 kD), high cysteine content, and sequence variation of VAR2CSA. A number of approaches have been taken to identify the combination of VAR2CSA domains and alleles that can induce broadly active antibodies that block adhesion of heterologous parasite isolates to CSA. This review summarizes these approaches, which have examined VAR2CSA fragments for binding activity, antigenicity with naturally acquired antibodies, and immunogenicity in animals for inducing anti-adhesion or surface-reactive antibodies. Two products are expected to enter human clinical studies in the near future based on N-terminal VAR2CSA fragments that have high binding affinity for CSA, and additional proteins preferentially expressed by placental parasites are also being examined for their potential contribution to a PM vaccine. Copyright © 2015. Published by Elsevier Ltd.

Laser mimicking mosquito bites for skin delivery of malaria sporozoite vaccines.

PubMed

Zhou, Chang; Chen, Xinyuan; Zhang, Qi; Wang, Ji; Wu, Mei X

2015-04-28

Immunization with radiation-attenuated sporozoites (RAS) via mosquito bites has been shown to induce sterile immunity against malaria in humans, but this route of vaccination is neither practical nor ethical. The importance of delivering RAS to the liver through circulation in eliciting immunity against this parasite has been recently verified by human studies showing that high-level protection was achieved only by intravenous (IV) administration of RAS, not by intradermal (ID) or subcutaneous (SC) vaccination. Here, we report in a murine model that ID inoculation of RAS into laser-illuminated skin confers immune protection against malarial infection almost as effectively as IV immunization. Brief illumination of the inoculation site with a low power 532 nm Nd:YAG laser enhanced the permeability of the capillary beneath the skin, owing to hemoglobin-specific absorbance of the light. The increased blood vessel permeability appeared to facilitate an association of RAS with blood vessel walls by an as-yet-unknown mechanism, ultimately promoting a 7-fold increase in RAS entering circulation and reaching the liver over ID administration. Accordingly, ID immunization of RAS at a laser-treated site stimulated much stronger sporozoite-specific antibody and CD8(+)IFN-γ(+) T cell responses than ID vaccination and provided nearly full protection against malarial infection, whereas ID immunization alone was ineffective. This novel, safe, and convenient strategy to augment efficacy of ID sporozoite-based vaccines warrants further investigation in large animals and in humans. Copyright © 2015 Elsevier B.V. All rights reserved.

Nonlinear Generation of shear flows and large scale magnetic fields by small scale

NASA Astrophysics Data System (ADS)

Aburjania, G.

2009-04-01

EGU2009-233 Nonlinear Generation of shear flows and large scale magnetic fields by small scale turbulence in the ionosphere by G. Aburjania Contact: George Aburjania, g.aburjania@gmail.com,aburj@mymail.ge

From research to phase III: preclinical, industrial and clinical development of the Sanofi Pasteur tetravalent dengue vaccine.

PubMed

Guy, Bruno; Barrere, Beatrice; Malinowski, Claire; Saville, Melanie; Teyssou, Remy; Lang, Jean

2011-09-23

Dengue vaccine development has reached a major milestone with the initiation, in 2010, of the first phase III clinical trial to investigate the Sanofi Pasteur CYD tetravalent dengue vaccine (TDV). The CYD TDV candidate is composed of four recombinant, live, attenuated vaccines (CYD-1-4) based on a yellow fever vaccine 17D (YFV 17D) backbone, each expressing the pre-membrane and envelope genes of one of the four dengue virus serotypes. The vaccine is genetically and phenotypically stable, non-hepatotropic, less neurovirulent than YFV 17D, and does not infect mosquitoes by the oral route. In vitro and in vivo preclinical studies showed that CYD TDV induces controlled stimulation of human dendritic cells, and significant immune responses in monkeys. Scale up and industrialization are being conducted in parallel with preclinical and clinical development to fulfill the needs of phase II/III trials, and to anticipate and facilitate supply and access to vaccine in the countries where the dengue disease burden makes it an urgent public health priority. The vaccine has now been administered to more than 6000 children and adults from dengue endemic and non-endemic areas and no safety concerns have arisen in any of the completed or ongoing trials. A three-dose vaccination regimen induces an immune response against all four serotypes in the large majority of vaccinees. Preexisting flavivirus immunity favors quicker and higher immune responses to CYD TDV, without adversely effecting clinical safety or increasing vaccine viremia. The observed level and nature of the cellular immune responses in humans are consistent with the good safety and immunogenicity profile of the vaccine. Preliminary results of an ongoing, proof-of-concept efficacy and large scale safety study in Thai children are expected by the end of 2012. Here we discuss the different steps and challenges of developing CYD TDV, from research to industrialization, and summarize some of the challenges to the successful

Large-scale Labeled Datasets to Fuel Earth Science Deep Learning Applications

NASA Astrophysics Data System (ADS)

Maskey, M.; Ramachandran, R.; Miller, J.

2017-12-01

Deep learning has revolutionized computer vision and natural language processing with various algorithms scaled using high-performance computing. However, generic large-scale labeled datasets such as the ImageNet are the fuel that drives the impressive accuracy of deep learning results. Large-scale labeled datasets already exist in domains such as medical science, but creating them in the Earth science domain is a challenge. While there are ways to apply deep learning using limited labeled datasets, there is a need in the Earth sciences for creating large-scale labeled datasets for benchmarking and scaling deep learning applications. At the NASA Marshall Space Flight Center, we are using deep learning for a variety of Earth science applications where we have encountered the need for large-scale labeled datasets. We will discuss our approaches for creating such datasets and why these datasets are just as valuable as deep learning algorithms. We will also describe successful usage of these large-scale labeled datasets with our deep learning based applications.

Large-Scale Coherent Vortex Formation in Two-Dimensional Turbulence

NASA Astrophysics Data System (ADS)

Orlov, A. V.; Brazhnikov, M. Yu.; Levchenko, A. A.

2018-04-01

The evolution of a vortex flow excited by an electromagnetic technique in a thin layer of a conducting liquid was studied experimentally. Small-scale vortices, excited at the pumping scale, merge with time due to the nonlinear interaction and produce large-scale structures—the inverse energy cascade is formed. The dependence of the energy spectrum in the developed inverse cascade is well described by the Kraichnan law k -5/3. At large scales, the inverse cascade is limited by cell sizes, and a large-scale coherent vortex flow is formed, which occupies almost the entire area of the experimental cell. The radial profile of the azimuthal velocity of the coherent vortex immediately after the pumping was switched off has been established for the first time. Inside the vortex core, the azimuthal velocity grows linearly along a radius and reaches a constant value outside the core, which agrees well with the theoretical prediction.

Associations between parents' satisfaction with provider communication and HPV vaccination behaviors.

PubMed

Kornides, Melanie L; Fontenot, Holly B; McRee, Annie-Laurie; Panozzo, Catherine A; Gilkey, Melissa B

2018-05-03

Despite increasing awareness of the importance of a provider recommendation for HPV vaccine, the U.S. has yet to achieve the Healthy people 2020 goal of 80% series completion among adolescents. This failure indicates a need for further examination of the modifiable influences on parents' decision-making. Healthcare providers can influence parents' HPV vaccination decision-making, but little is known about parents' perspectives on the counseling they receive. We sought to assess U.S. parents' satisfaction with provider communication about HPV vaccine and associations with vaccination behaviors. Parents of 11-to-17-year-old adolescents who discussed HPV vaccination with a healthcare provider at least once (n = 795) completed our online survey in Fall 2016. We assessed their satisfaction with the discussion using the HPV Vaccine Communication Satisfaction Scale (α = 0.94). We examined associations between satisfaction (categorized as low, moderate, or high), and three vaccination behaviors: refusal/delay, series initiation (≥1 dose), and continuation (≥2 doses among initiators) using multivariable logistic regression. Most parents reported high (36%) or moderate (38%) satisfaction with provider communication about HPV vaccination; fewer reported low (26%) satisfaction. Moderately satisfied parents (vs. low) had lower odds of refusal/delay (aOR = 0.59, 95% CI: 0.38-0.89), and higher odds of initiation (aOR = 1.71, 95% CI:1.15-2.55) and continuation (aOR = 2.05, 95% CI: 1.24-3.40). The associations were stronger for highly satisfied parents (refusal/delay aOR = 0.45, 95% CI: 0.29-0.70, initiation aOR = 3.59, 95% CI: 2.23-5.78, and continuation aOR = 4.08, 95% CI: 2.38-7.01). Our study suggests that parent satisfaction with provider communication may play an important role in HPV vaccination decision-making. Yet, communication satisfaction has been largely unexamined in the HPV-vaccine literature to date. We introduce a brief, 7-item

Robust regression for large-scale neuroimaging studies.

PubMed

Fritsch, Virgile; Da Mota, Benoit; Loth, Eva; Varoquaux, Gaël; Banaschewski, Tobias; Barker, Gareth J; Bokde, Arun L W; Brühl, Rüdiger; Butzek, Brigitte; Conrod, Patricia; Flor, Herta; Garavan, Hugh; Lemaitre, Hervé; Mann, Karl; Nees, Frauke; Paus, Tomas; Schad, Daniel J; Schümann, Gunter; Frouin, Vincent; Poline, Jean-Baptiste; Thirion, Bertrand

2015-05-01

Multi-subject datasets used in neuroimaging group studies have a complex structure, as they exhibit non-stationary statistical properties across regions and display various artifacts. While studies with small sample sizes can rarely be shown to deviate from standard hypotheses (such as the normality of the residuals) due to the poor sensitivity of normality tests with low degrees of freedom, large-scale studies (e.g. >100 subjects) exhibit more obvious deviations from these hypotheses and call for more refined models for statistical inference. Here, we demonstrate the benefits of robust regression as a tool for analyzing large neuroimaging cohorts. First, we use an analytic test based on robust parameter estimates; based on simulations, this procedure is shown to provide an accurate statistical control without resorting to permutations. Second, we show that robust regression yields more detections than standard algorithms using as an example an imaging genetics study with 392 subjects. Third, we show that robust regression can avoid false positives in a large-scale analysis of brain-behavior relationships with over 1500 subjects. Finally we embed robust regression in the Randomized Parcellation Based Inference (RPBI) method and demonstrate that this combination further improves the sensitivity of tests carried out across the whole brain. Altogether, our results show that robust procedures provide important advantages in large-scale neuroimaging group studies. Copyright © 2015 Elsevier Inc. All rights reserved.

Intensive agriculture erodes β-diversity at large scales.

PubMed

Karp, Daniel S; Rominger, Andrew J; Zook, Jim; Ranganathan, Jai; Ehrlich, Paul R; Daily, Gretchen C

2012-09-01

Biodiversity is declining from unprecedented land conversions that replace diverse, low-intensity agriculture with vast expanses under homogeneous, intensive production. Despite documented losses of species richness, consequences for β-diversity, changes in community composition between sites, are largely unknown, especially in the tropics. Using a 10-year data set on Costa Rican birds, we find that low-intensity agriculture sustained β-diversity across large scales on a par with forest. In high-intensity agriculture, low local (α) diversity inflated β-diversity as a statistical artefact. Therefore, at small spatial scales, intensive agriculture appeared to retain β-diversity. Unlike in forest or low-intensity systems, however, high-intensity agriculture also homogenised vegetation structure over large distances, thereby decoupling the fundamental ecological pattern of bird communities changing with geographical distance. This ~40% decline in species turnover indicates a significant decline in β-diversity at large spatial scales. These findings point the way towards multi-functional agricultural systems that maintain agricultural productivity while simultaneously conserving biodiversity. © 2012 Blackwell Publishing Ltd/CNRS.

Tools for Large-Scale Mobile Malware Analysis

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

Bierma, Michael

Analyzing mobile applications for malicious behavior is an important area of re- search, and is made di cult, in part, by the increasingly large number of appli- cations available for the major operating systems. There are currently over 1.2 million apps available in both the Google Play and Apple App stores (the respec- tive o cial marketplaces for the Android and iOS operating systems)[1, 2]. Our research provides two large-scale analysis tools to aid in the detection and analysis of mobile malware. The rst tool we present, Andlantis, is a scalable dynamic analysis system capa- ble of processing over 3000more » Android applications per hour. Traditionally, Android dynamic analysis techniques have been relatively limited in scale due to the compu- tational resources required to emulate the full Android system to achieve accurate execution. Andlantis is the most scalable Android dynamic analysis framework to date, and is able to collect valuable forensic data, which helps reverse-engineers and malware researchers identify and understand anomalous application behavior. We discuss the results of running 1261 malware samples through the system, and provide examples of malware analysis performed with the resulting data. While techniques exist to perform static analysis on a large number of appli- cations, large-scale analysis of iOS applications has been relatively small scale due to the closed nature of the iOS ecosystem, and the di culty of acquiring appli- cations for analysis. The second tool we present, iClone, addresses the challenges associated with iOS research in order to detect application clones within a dataset of over 20,000 iOS applications.« less

The Spanish royal philanthropic expedition to bring smallpox vaccination to the New World and Asia in the 19th century.

PubMed

Franco-Paredes, Carlos; Lammoglia, Lorena; Santos-Preciado, José Ignacio

2005-11-01

The New World was ravaged by smallpox for several centuries after the Spanish conquest. Jenner's discovery of the smallpox vaccine made possible the prevention and control of smallpox epidemics. In response to a large outbreak of smallpox in the Spanish colonies, King Charles IV appointed Francisco Xavier de Balmis to lead an expedition that would introduce Jenner's vaccine to these colonies. During the journey, the vaccine was kept viable by passing it from arm to arm in orphaned children, who were brought along expressly for that purpose and remained under the care of the orphanage's director. This expedition was the first large scale mass vaccination of its kind. The historic legacy of this pioneering event in international health should be revisited in the current era of persistent inequalities in global health.

Identifying Attenuating Mutations: Tools for a New Vaccine Design against Flaviviruses.

PubMed

Khou, Cécile; Pardigon, Nathalie

2017-01-01

Emerging Flaviviruses pose an increasing threat to global human health. To date, human vaccines against yellow fever virus (YFV), Japanese encephalitis virus (JEV), dengue virus (DV), and tick-borne encephalitis virus (TBEV) exist. However, there is no human vaccine against other Flaviviruses such as Zika virus (ZIKV) and West Nile virus (WNV). In order to restrict their spread and to protect populations against the diseases they induce, vaccines against these emerging viruses must be designed. Obtaining new live attenuated Flavivirus vaccines using molecular biology methods is now possible. Molecular infectious clones of the parental viruses are relatively easy to generate. Key mutations present in live attenuated vaccines or mutations known to have a key role in the Flavivirus life cycle and/or interactions with their hosts can be identified by sequencing, and are then inserted in infectious clones by site-directed mutagenesis. More recently, the use of chimeric viruses and large-scale reencoding and introduction of microRNA target sequences have also been tested. Indeed, a combination of these methods will help in designing new generations of vaccines against emerging and reemerging Flaviviruses. © 2017 S. Karger AG, Basel.

Stability of large-scale systems.

NASA Technical Reports Server (NTRS)

Siljak, D. D.

1972-01-01

The purpose of this paper is to present the results obtained in stability study of large-scale systems based upon the comparison principle and vector Liapunov functions. The exposition is essentially self-contained, with emphasis on recent innovations which utilize explicit information about the system structure. This provides a natural foundation for the stability theory of dynamic systems under structural perturbations.

Real-time simulation of large-scale floods

NASA Astrophysics Data System (ADS)

Liu, Q.; Qin, Y.; Li, G. D.; Liu, Z.; Cheng, D. J.; Zhao, Y. H.

2016-08-01

According to the complex real-time water situation, the real-time simulation of large-scale floods is very important for flood prevention practice. Model robustness and running efficiency are two critical factors in successful real-time flood simulation. This paper proposed a robust, two-dimensional, shallow water model based on the unstructured Godunov- type finite volume method. A robust wet/dry front method is used to enhance the numerical stability. An adaptive method is proposed to improve the running efficiency. The proposed model is used for large-scale flood simulation on real topography. Results compared to those of MIKE21 show the strong performance of the proposed model.

The State of Vaccine Confidence 2016: Global Insights Through a 67-Country Survey.

PubMed

Larson, Heidi J; de Figueiredo, Alexandre; Xiahong, Zhao; Schulz, William S; Verger, Pierre; Johnston, Iain G; Cook, Alex R; Jones, Nick S

2016-10-01

Public trust in immunization is an increasingly important global health issue. Losses in confidence in vaccines and immunization programmes can lead to vaccine reluctance and refusal, risking disease outbreaks and challenging immunization goals in high- and low-income settings. National and international immunization stakeholders have called for better monitoring of vaccine confidence to identify emerging concerns before they evolve into vaccine confidence crises. We perform a large-scale, data-driven study on worldwide attitudes to immunizations. This survey - which we believe represents the largest survey on confidence in immunization to date - examines perceptions of vaccine importance, safety, effectiveness, and religious compatibility among 65,819 individuals across 67 countries. Hierarchical models are employed to probe relationships between individual- and country-level socio-economic factors and vaccine attitudes obtained through the four-question, Likert-scale survey. Overall sentiment towards vaccinations is positive across all 67 countries, however there is wide variability between countries and across world regions. Vaccine-safety related sentiment is particularly negative in the European region, which has seven of the ten least confident countries, with 41% of respondents in France and 36% of respondents in Bosnia & Herzegovina reporting that they disagree that vaccines are safe (compared to a global average of 13%). The oldest age group (65+) and Roman Catholics (amongst all faiths surveyed) are associated with positive views on vaccine sentiment, while the Western Pacific region reported the highest level of religious incompatibility with vaccines. Countries with high levels of schooling and good access to health services are associated with lower rates of positive sentiment, pointing to an emerging inverse relationship between vaccine sentiments and socio-economic status. Regular monitoring of vaccine attitudes - coupled with monitoring of local

Malaria vaccine offers hope. International / Africa.

PubMed

1995-03-13

Colombian professor Manuel Patarroyo developed a new malaria vaccine (SPF66). In February 1995, WHO and the Colombian government agreed to establish a manufacturing plant in Colombia for mass production of SPF66. This vaccine is likely to be available to persons in Africa, where 90% of all annual global cases live. In fact, Africa witnesses one million of 1.5 million annual malaria cases. Many children die from malaria. An extensive clinical trial of the SPF66 vaccine in Colombia achieved a 22-77% protection rate. The young and the very old had the high protection rates. A series of human clinical trials in the Gambia and Tanzania indicate that SPF66 produces a strong immune response against malaria without any harmful side effects. The results of field tests in the Gambia and Thailand and of trials in Colombia are expected in 1995. If the vaccine could reduce the incidence of malaria by just 50%, the lives of as many as 500,000 African children could be saved. SPF66 contains a combination of synthetic peptides (=or 2 amino acids). Mass production would make it affordable (estimated $5/injection). At least five other malaria vaccines hold promise and are ready for human testing in endemic countries. SPF66 is approximately three years ahead of all other promising malaria vaccines. 20 more vaccines are in the development stage. The large scale production of SPF66 in Colombia could begin within three years. Professor Patarroyo has financed his 12-year-old research himself because he wants to protect the lives of persons in developing countries. In 1992, the Congo's president petitioned the international community at the WHO summit in Amsterdam to join the fight against malaria since it is now in a position to defeat malaria since it finished the cold war.

Hub nodes inhibit the outbreak of epidemic under voluntary vaccination

NASA Astrophysics Data System (ADS)

Zhang, Haifeng; Zhang, Jie; Zhou, Changsong; Small, Michael; Wang, Binghong

2010-02-01

It is commonly believed that epidemic spreading on scale-free networks is difficult to control and that the disease can spread even with a low infection rate, lacking an epidemic threshold. In this paper, we study epidemic spreading on complex networks under the framework of game theory, in which a voluntary vaccination strategy is incorporated. In particular, individuals face the 'dilemma' of vaccination: they have to decide whether or not to vaccinate according to the trade-off between the risk and the side effects or cost of vaccination. Remarkably and quite excitingly, we find that disease outbreak can be more effectively inhibited on scale-free networks than on random networks. This is because the hub nodes of scale-free networks are more inclined to take self-vaccination after balancing the pros and cons. This result is encouraging as it indicates that real-world networks, which are often claimed to be scale free, can be favorably and easily controlled under voluntary vaccination. Our work provides a way of understanding how to prevent the outbreak of diseases under voluntary vaccination, and is expected to provide valuable information on effective disease control and appropriate decision-making.

Large scale anomalies in the microwave background: causation and correlation.

PubMed

Aslanyan, Grigor; Easther, Richard

2013-12-27

Most treatments of large scale anomalies in the microwave sky are a posteriori, with unquantified look-elsewhere effects. We contrast these with physical models of specific inhomogeneities in the early Universe which can generate these apparent anomalies. Physical models predict correlations between candidate anomalies and the corresponding signals in polarization and large scale structure, reducing the impact of cosmic variance. We compute the apparent spatial curvature associated with large-scale inhomogeneities and show that it is typically small, allowing for a self-consistent analysis. As an illustrative example we show that a single large plane wave inhomogeneity can contribute to low-l mode alignment and odd-even asymmetry in the power spectra and the best-fit model accounts for a significant part of the claimed odd-even asymmetry. We argue that this approach can be generalized to provide a more quantitative assessment of potential large scale anomalies in the Universe.

Effects of biasing on the galaxy power spectrum at large scales

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

Beltran Jimenez, Jose; Departamento de Fisica Teorica, Universidad Complutense de Madrid, 28040, Madrid; Durrer, Ruth

2011-05-15

In this paper we study the effect of biasing on the power spectrum at large scales. We show that even though nonlinear biasing does introduce a white noise contribution on large scales, the P(k){proportional_to}k{sup n} behavior of the matter power spectrum on large scales may still be visible and above the white noise for about one decade. We show, that the Kaiser biasing scheme which leads to linear bias of the correlation function on large scales, also generates a linear bias of the power spectrum on rather small scales. This is a consequence of the divergence on small scales ofmore » the pure Harrison-Zeldovich spectrum. However, biasing becomes k dependent if we damp the underlying power spectrum on small scales. We also discuss the effect of biasing on the baryon acoustic oscillations.« less

Yellow fever vaccine: an effective vaccine for travelers.

PubMed

Verma, Ramesh; Khanna, Pardeep; Chawla, Suraj

2014-01-01

Yellow fever (YF) is an acute viral communicable disease transmitted by an arbovirus of the Flavivirus genus. It is primarily a zoonotic disease, especially the monkeys. Worldwide, an estimated 200,000 cases of yellow fever occurred each year, and the case-fatality rate is ~15%. Forty-five endemic countries in Africa and Latin America, with a population of close to 1 billion, are at risk. Up to 50% of severely affected persons from YF die without treatment. During 2009, 55 cases and 18 deaths were reported from Brazil, Colombia, and Peru. Brazil reported the maximum number of cases and death, i.e., 42 cases with 11 deaths. From January 2010 to March 2011, outbreaks of YF were reported to the WHO by Cameroon, Democratic Republic of Congo, Cote d'Ivoire, Guinea, Sierra Leone, Senegal, and Uganda. Cases were also reported in three northern districts of Abim, Agago, and Kitugun near the border with South Sudan. YF usually causes fever, muscle pain with prominent backache, headache, shivers, loss of appetite, and nausea or vomiting. Most patients improve, and their symptoms disappear after 3 to 4 d. Half of the patients who enter the toxic phase die within 10-14 d, while the rest recover without significant organ damage. Vaccination has been the single most important measure for preventing YF. The 17D-204 YF vaccine is a freeze-dried, live attenuated, highly effective vaccine. It is available in single-dose or multi-dose vials and should be stored at 2-8 °C. It is reconstituted with normal saline and should be used within 1 h of reconstitution. The 0.5 mL dose is delivered subcutaneously. Revaccination is recommended every 10 y for people at continued risk of exposure to yellow fever virus (YFV). This vaccine is available worldwide. Travelers, especially to Africa or Latin America from Asia, must have a certificate documenting YF vaccination, which is required by certain countries for entry under the International Health Regulations (IHR) of the WHO.

Statistical Measures of Large-Scale Structure

NASA Astrophysics Data System (ADS)

Vogeley, Michael; Geller, Margaret; Huchra, John; Park, Changbom; Gott, J. Richard

1993-12-01

\\inv Mpc} To quantify clustering in the large-scale distribution of galaxies and to test theories for the formation of structure in the universe, we apply statistical measures to the CfA Redshift Survey. This survey is complete to m_{B(0)}=15.5 over two contiguous regions which cover one-quarter of the sky and include ~ 11,000 galaxies. The salient features of these data are voids with diameter 30-50\\hmpc and coherent dense structures with a scale ~ 100\\hmpc. Comparison with N-body simulations rules out the ``standard" CDM model (Omega =1, b=1.5, sigma_8 =1) at the 99% confidence level because this model has insufficient power on scales lambda >30\\hmpc. An unbiased open universe CDM model (Omega h =0.2) and a biased CDM model with non-zero cosmological constant (Omega h =0.24, lambda_0 =0.6) match the observed power spectrum. The amplitude of the power spectrum depends on the luminosity of galaxies in the sample; bright (L>L(*) ) galaxies are more strongly clustered than faint galaxies. The paucity of bright galaxies in low-density regions may explain this dependence. To measure the topology of large-scale structure, we compute the genus of isodensity surfaces of the smoothed density field. On scales in the ``non-linear" regime, <= 10\\hmpc, the high- and low-density regions are multiply-connected over a broad range of density threshold, as in a filamentary net. On smoothing scales >10\\hmpc, the topology is consistent with statistics of a Gaussian random field. Simulations of CDM models fail to produce the observed coherence of structure on non-linear scales (>95% confidence level). The underdensity probability (the frequency of regions with density contrast delta rho //lineρ=-0.8) depends strongly on the luminosity of galaxies; underdense regions are significantly more common (>2sigma ) in bright (L>L(*) ) galaxy samples than in samples which include fainter galaxies.

Cosmic strings and the large-scale structure

NASA Technical Reports Server (NTRS)

Stebbins, Albert

1988-01-01

A possible problem for cosmic string models of galaxy formation is presented. If very large voids are common and if loop fragmentation is not much more efficient than presently believed, then it may be impossible for string scenarios to produce the observed large-scale structure with Omega sub 0 = 1 and without strong environmental biasing.

Coronal hole evolution by sudden large scale changes

NASA Technical Reports Server (NTRS)

Nolte, J. T.; Gerassimenko, M.; Krieger, A. S.; Solodyna, C. V.

1978-01-01

Sudden shifts in coronal-hole boundaries observed by the S-054 X-ray telescope on Skylab between May and November, 1973, within 1 day of CMP of the holes, at latitudes not exceeding 40 deg, are compared with the long-term evolution of coronal-hole area. It is found that large-scale shifts in boundary locations can account for most if not all of the evolution of coronal holes. The temporal and spatial scales of these large-scale changes imply that they are the results of a physical process occurring in the corona. It is concluded that coronal holes evolve by magnetic-field lines' opening when the holes are growing, and by fields' closing as the holes shrink.

New probes of Cosmic Microwave Background large-scale anomalies

NASA Astrophysics Data System (ADS)

Aiola, Simone

Fifty years of Cosmic Microwave Background (CMB) data played a crucial role in constraining the parameters of the LambdaCDM model, where Dark Energy, Dark Matter, and Inflation are the three most important pillars not yet understood. Inflation prescribes an isotropic universe on large scales, and it generates spatially-correlated density fluctuations over the whole Hubble volume. CMB temperature fluctuations on scales bigger than a degree in the sky, affected by modes on super-horizon scale at the time of recombination, are a clean snapshot of the universe after inflation. In addition, the accelerated expansion of the universe, driven by Dark Energy, leaves a hardly detectable imprint in the large-scale temperature sky at late times. Such fundamental predictions have been tested with current CMB data and found to be in tension with what we expect from our simple LambdaCDM model. Is this tension just a random fluke or a fundamental issue with the present model? In this thesis, we present a new framework to probe the lack of large-scale correlations in the temperature sky using CMB polarization data. Our analysis shows that if a suppression in the CMB polarization correlations is detected, it will provide compelling evidence for new physics on super-horizon scale. To further analyze the statistical properties of the CMB temperature sky, we constrain the degree of statistical anisotropy of the CMB in the context of the observed large-scale dipole power asymmetry. We find evidence for a scale-dependent dipolar modulation at 2.5sigma. To isolate late-time signals from the primordial ones, we test the anomalously high Integrated Sachs-Wolfe effect signal generated by superstructures in the universe. We find that the detected signal is in tension with the expectations from LambdaCDM at the 2.5sigma level, which is somewhat smaller than what has been previously argued. To conclude, we describe the current status of CMB observations on small scales, highlighting the