Evaluation of Immune Responses Mediated by Listeria-Stimulated Human Dendritic Cells: Implications for Cancer Vaccine Therapy

DTIC Science & Technology

2013-07-01

by Listeria -Stimulated Human Dendritic Cells: Implications for Cancer Vaccine Therapy PRINCIPAL INVESTIGATOR: David J. Chung, MD, PhD...2013 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER W81XWH-11-1-0384 Evaluation of Immune Responses Mediated by Listeria -Stimulated Human Dendritic...Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT The purpose of this project is to study the immunomodulatory effect of Listeria on human

Vaccination with Irradiated Autologous Melanoma Cells Engineered to Secrete Human Granulocyte--Macrophage Colony-Stimulating Factor Generates Potent Antitumor Immunity in Patients with Metastatic Melanoma

NASA Astrophysics Data System (ADS)

Soiffer, Robert; Lynch, Thomas; Mihm, Martin; Jung, Ken; Rhuda, Catherine; Schmollinger, Jan C.; Hodi, F. Stephen; Liebster, Laura; Lam, Prudence; Mentzer, Steven; Singer, Samuel; Tanabe, Kenneth K.; Benedict Cosimi, A.; Duda, Rosemary; Sober, Arthur; Bhan, Atul; Daley, John; Neuberg, Donna; Parry, Gordon; Rokovich, Joseph; Richards, Laurie; Drayer, Jan; Berns, Anton; Clift, Shirley; Cohen, Lawrence K.; Mulligan, Richard C.; Dranoff, Glenn

1998-10-01

We conducted a Phase I clinical trial investigating the biologic activity of vaccination with irradiated autologous melanoma cells engineered to secrete human granulocyte--macrophage colony-stimulating factor in patients with metastatic melanoma. Immunization sites were intensely infiltrated with T lymphocytes, dendritic cells, macrophages, and eosinophils in all 21 evaluable patients. Although metastatic lesions resected before vaccination were minimally infiltrated with cells of the immune system in all patients, metastatic lesions resected after vaccination were densely infiltrated with T lymphocytes and plasma cells and showed extensive tumor destruction (at least 80%), fibrosis, and edema in 11 of 16 patients examined. Antimelanoma cytotoxic T cell and antibody responses were associated with tumor destruction. These results demonstrate that vaccination with irradiated autologous melanoma cells engineered to secrete granulocyte--macrophage colony-stimulating factor stimulates potent antitumor immunity in humans with metastatic melanoma.

In vitro stimulation with a strongly pulsed electromagnetic field on rat basophilic leukemia cells

NASA Astrophysics Data System (ADS)

Choi, J. W.; Shin, S. C.; Kim, S.; Chung, E. R.; Bang, J. H.; Cho, G. I.; Choi, S. D.; Park, Y. S.; Jang, T. S.; Yoo, Y. M.; Lee, S. S.; Hwang, D. G.

2010-05-01

In this study, the effects of pulsed electromagnetic field stimulation with a strong magnetic field on rat basophilic leukemia (RBL-2H3) cells were investigated to confirm the efficacy of the magnetic stimulator for biomedical applications. The maximum intensity of the magnetic field generated from the stimulation coil was 0.203 T, and the transition time was 126 μs. The oscillation time and frequency of the pulsed field were almost 0.1 ms and 8 kHz, respectively. The cell count as well as the mRNA expression and DNA sequence of the cytokine genes, such as the tumor necrosis factor-α (TNF-α) and interleukin-4 (IL-4), of the stimulated RBL-2H3 cells were analyzed with a hemocytometer and via reverse transcriptase polymerase chain reaction to determine the physiological response under a strong pulse field. After 12 h stimulation, cell death was observed at an increasing scale with the increase in the stimulation time. On the other hand, the cells that were stimulated for 10 min almost doubled as the interval time between the stimulations was extended.

Increasing exposure to antibody-stimulating proteins and polysaccharides in vaccines is not associated with risk of autism.

PubMed

DeStefano, Frank; Price, Cristofer S; Weintraub, Eric S

2013-08-01

To evaluate the association between autism and the level of immunologic stimulation received from vaccines administered during the first 2 years of life. We analyzed data from a case-control study conducted in 3 managed care organizations (MCOs) of 256 children with autism spectrum disorder (ASD) and 752 control children matched on birth year, sex, and MCO. In addition to the broader category of ASD, we also evaluated autistic disorder and ASD with regression. ASD diagnoses were validated through standardized in-person evaluations. Exposure to total antibody-stimulating proteins and polysaccharides from vaccines was determined by summing the antigen content of each vaccine received, as obtained from immunization registries and medical records. Potential confounding factors were ascertained from parent interviews and medical charts. Conditional logistic regression was used to assess associations between ASD outcomes and exposure to antigens in selected time periods. The aOR (95% CI) of ASD associated with each 25-unit increase in total antigen exposure was 0.999 (0.994-1.003) for cumulative exposure to age 3 months, 0.999 (0.997-1.001) for cumulative exposure to age 7 months, and 0.999 (0.998-1.001) for cumulative exposure to age 2 years. Similarly, no increased risk was found for autistic disorder or ASD with regression. In this study of MCO members, increasing exposure to antibody-stimulating proteins and polysaccharides in vaccines during the first 2 years of life was not related to the risk of developing an ASD. Copyright © 2013 Mosby, Inc. All rights reserved.

Applications and challenges of multivalent recombinant vaccines

PubMed Central

Naim, Hussein Y.

2013-01-01

The exceptional discoveries of antigen/gene delivery systems have allowed the development of novel prophylactic and therapeutic vaccine candidates. The vaccine candidates employ various antigen-delivery systems, particularly recombinant viral vectors. Recombinant viral vectors are experimental vaccines similar to DNA vaccines, but they use attenuated viruses or bacterium as a carrier “vector” to introduce microbial DNA to cells of the body. They closely mimic a natural infection and therefore can efficiently stimulate the immune system. Although such recombinant vectors may face extensive preclinical testing and will possibly have to meet stringent regulatory requirements, some of these vectors (e.g. measles virus vectors) may benefit from the profound industrial and clinical experience of the parent vaccine. Most notably, novel vaccines based on live attenuated viruses combine the induction of broad, strong and persistent immune responses with acceptable safety profiles. We assess certain technologies in light of their use against human immunodeficiency virus (HIV). PMID:23249651

Subcomponent vaccine based on CTA1-DD adjuvant with incorporated UreB class II peptides stimulates protective Helicobacter pylori immunity.

PubMed

Nedrud, John G; Bagheri, Nayer; Schön, Karin; Xin, Wei; Bergroth, Hilda; Eliasson, Dubravka Grdic; Lycke, Nils Y

2013-01-01

A mucosal vaccine against Helicobacter pylori infection could help prevent gastric cancers and peptic ulcers. While previous attempts to develop such a vaccine have largely failed because of the requirement for safe and effective adjuvants or large amounts of well defined antigens, we have taken a unique approach to combining our strong mucosal CTA1-DD adjuvant with selected peptides from urease B (UreB). The protective efficacy of the selected peptides together with cholera toxin (CT) was first confirmed. However, CT is a strong adjuvant that unfortunately is precluded from clinical use because of its toxicity. To circumvent this problem we have developed a derivative of CT, the CTA1-DD adjuvant, that has been found safe in non-human primates and equally effective compared to CT when used intranasally. We genetically fused the selected peptides into the CTA1-DD plasmid and found after intranasal immunizations of Balb/c mice using purified CTA1-DD with 3 copies of an H. pylori urease T cell epitope (CTA1-UreB3T-DD) that significant protection was stimulated against a live challenge infection. Protection was, however, weaker than with the gold standard, bacterial lysate+CT, but considering that we only used a single epitope in nanomolar amounts the results convey optimism. Protection was associated with enhanced Th1 and Th17 immunity, but immunizations in IL-17A-deficient mice revealed that IL-17 may not be essential for protection. Taken together, we have provided evidence for the rational design of an effective mucosal subcomponent vaccine against H. pylori infection based on well selected protective epitopes from relevant antigens incorporated into the CTA1-DD adjuvant platform.

Age and Influenza-Specific Pre-Vaccination Antibodies Strongly Affect Influenza Vaccine Responses in the Icelandic Population whereas Disease and Medication Have Small Effects

PubMed Central

Olafsdottir, Thorunn A.; Alexandersson, Kristjan F.; Sveinbjornsson, Gardar; Lapini, Giulia; Palladino, Laura; Montomoli, Emanuele; Del Giudice, Giuseppe; Gudbjartsson, Daniel F.; Jonsdottir, Ingileif

2018-01-01

Influenza vaccination remains the best strategy for the prevention of influenza virus-related disease and reduction of disease severity and mortality. However, there is large individual variation in influenza vaccine responses. In this study, we investigated the effects of gender, age, underlying diseases, and medication on vaccine responses in 1,852 Icelanders of broad age range who received trivalent inactivated influenza virus vaccination in 2012, 2013, or 2015. Hemagglutination inhibition (HAI) and microneutralization (MN) titers were measured in pre- and post-vaccination sera. Of the variables tested, the strongest association was with level of pre-vaccination titer that explained a major part of the variance observed in post-vaccination titers, ranging from 19 to 29%, and from 7 to 21% in fold change (FC), depending on the strain and serological (HAI or MN) analysis performed. Thus, increasing pre-vaccination titer associated with decreasing FC (P = 1.1 × 10−99–8.6 × 10−30) and increasing post-vaccination titer (P = 2.1 × 10−159–1.1 × 10−123). Questionnaires completed by 87% of the participants revealed that post-vaccination HAI titer showed association with repeated previous influenza vaccinations. Gender had no effect on vaccine response whereas age had a strong effect and explained 1.6–3.1% of HAI post-vaccination titer variance and 3.1% of H1N1 MN titer variance. Vaccine response, both fold increase and seroprotection rate (percentage of individuals reaching HAI ≥ 40 or MN ≥ 20), was higher in vaccinees ≤37 years of age (YoA) than all other age groups. Furthermore, a reduction was observed in the H1N1 MN titer in people ≥63 YoA, demonstrating a decreased neutralizing functionality of vaccine-induced antibodies at older age. We tested the effects of underlying autoimmune diseases, asthma and allergic diseases and did not observe significant associations with vaccine responses. Intake of immune

A glycoprotein subunit vaccine elicits a strong Rift Valley fever virus neutralizing antibody response in sheep.

PubMed

Faburay, Bonto; Lebedev, Maxim; McVey, D Scott; Wilson, William; Morozov, Igor; Young, Alan; Richt, Juergen A

2014-10-01

Rift Valley fever virus (RVFV), a member of the Bunyaviridae family, is a mosquito-borne zoonotic pathogen that causes serious morbidity and mortality in livestock and humans. The recent spread of the virus beyond its traditional endemic boundaries in Africa to the Arabian Peninsula coupled with the presence of susceptible vectors in nonendemic countries has created increased interest in RVF vaccines. Subunit vaccines composed of specific virus proteins expressed in eukaryotic or prokaryotic expression systems are shown to elicit neutralizing antibodies in susceptible hosts. RVFV structural proteins, amino-terminus glycoprotein (Gn), and carboxyl-terminus glycoprotein (Gc), were expressed using a recombinant baculovirus expression system. The recombinant proteins were reconstituted as a GnGc subunit vaccine formulation and evaluated for immunogenicity in a target species, sheep. Six sheep were each immunized with a primary dose of 50 μg of each vaccine immunogen with the adjuvant montanide ISA25; at day 21, postvaccination, each animal received a second dose of the same vaccine. The vaccine induced a strong antibody response in all animals as determined by indirect enzyme-linked immunosorbent assay (ELISA). A plaque reduction neutralization test (PRNT80) showed the primary dose of the vaccine was sufficient to elicit potentially protective virus neutralizing antibody titers ranging from 40 to 160, and the second vaccine dose boosted the titer to more than 1280. Furthermore, all animals tested positive for neutralizing antibodies at day 328 postvaccination. ELISA analysis using the recombinant nucleocapsid protein as a negative marker antigen indicated that the vaccine candidate is DIVA (differentiating infected from vaccinated animals) compatible and represents a promising vaccine platform for RVFV infection in susceptible species.

A Glycoprotein Subunit Vaccine Elicits a Strong Rift Valley Fever Virus Neutralizing Antibody Response in Sheep

PubMed Central

Lebedev, Maxim; McVey, D. Scott; Wilson, William; Morozov, Igor; Young, Alan

2014-01-01

Abstract Rift Valley fever virus (RVFV), a member of the Bunyaviridae family, is a mosquito-borne zoonotic pathogen that causes serious morbidity and mortality in livestock and humans. The recent spread of the virus beyond its traditional endemic boundaries in Africa to the Arabian Peninsula coupled with the presence of susceptible vectors in nonendemic countries has created increased interest in RVF vaccines. Subunit vaccines composed of specific virus proteins expressed in eukaryotic or prokaryotic expression systems are shown to elicit neutralizing antibodies in susceptible hosts. RVFV structural proteins, amino-terminus glycoprotein (Gn), and carboxyl-terminus glycoprotein (Gc), were expressed using a recombinant baculovirus expression system. The recombinant proteins were reconstituted as a GnGc subunit vaccine formulation and evaluated for immunogenicity in a target species, sheep. Six sheep were each immunized with a primary dose of 50 μg of each vaccine immunogen with the adjuvant montanide ISA25; at day 21, postvaccination, each animal received a second dose of the same vaccine. The vaccine induced a strong antibody response in all animals as determined by indirect enzyme-linked immunosorbent assay (ELISA). A plaque reduction neutralization test (PRNT80) showed the primary dose of the vaccine was sufficient to elicit potentially protective virus neutralizing antibody titers ranging from 40 to 160, and the second vaccine dose boosted the titer to more than 1280. Furthermore, all animals tested positive for neutralizing antibodies at day 328 postvaccination. ELISA analysis using the recombinant nucleocapsid protein as a negative marker antigen indicated that the vaccine candidate is DIVA (differentiating infected from vaccinated animals) compatible and represents a promising vaccine platform for RVFV infection in susceptible species. PMID:25325319

Subcomponent Vaccine Based on CTA1-DD Adjuvant with Incorporated UreB Class II Peptides Stimulates Protective Helicobacter pylori Immunity

PubMed Central

Nedrud, John G.; Bagheri, Nayer; Schön, Karin; Xin, Wei; Bergroth, Hilda; Eliasson, Dubravka Grdic; Lycke, Nils Y.

2013-01-01

A mucosal vaccine against Helicobacter pylori infection could help prevent gastric cancers and peptic ulcers. While previous attempts to develop such a vaccine have largely failed because of the requirement for safe and effective adjuvants or large amounts of well defined antigens, we have taken a unique approach to combining our strong mucosal CTA1-DD adjuvant with selected peptides from urease B (UreB). The protective efficacy of the selected peptides together with cholera toxin (CT) was first confirmed. However, CT is a strong adjuvant that unfortunately is precluded from clinical use because of its toxicity. To circumvent this problem we have developed a derivative of CT, the CTA1-DD adjuvant, that has been found safe in non-human primates and equally effective compared to CT when used intranasally. We genetically fused the selected peptides into the CTA1-DD plasmid and found after intranasal immunizations of Balb/c mice using purified CTA1-DD with 3 copies of an H. pylori urease T cell epitope (CTA1-UreB3T-DD) that significant protection was stimulated against a live challenge infection. Protection was, however, weaker than with the gold standard, bacterial lysate+CT, but considering that we only used a single epitope in nanomolar amounts the results convey optimism. Protection was associated with enhanced Th1 and Th17 immunity, but immunizations in IL-17A-deficient mice revealed that IL-17 may not be essential for protection. Taken together, we have provided evidence for the rational design of an effective mucosal subcomponent vaccine against H. pylori infection based on well selected protective epitopes from relevant antigens incorporated into the CTA1-DD adjuvant platform. PMID:24391754

Colonic Immune Stimulation by Targeted Oral Vaccine

PubMed Central

Kathania, Mahesh; Zadeh, Mojgan; Lightfoot, Yaíma L.; Roman, Robert M.; Sahay, Bikash; Abbott, Jeffrey R.; Mohamadzadeh, Mansour

2013-01-01

Background Currently, sufficient data exist to support the use of lactobacilli as candidates for the development of new oral targeted vaccines. To this end, we have previously shown that Lactobacillus gasseri expressing the protective antigen (PA) component of anthrax toxin genetically fused to a dendritic cell (DC)-binding peptide (DCpep) induced efficacious humoral and T cell-mediated immune responses against Bacillus anthracis Sterne challenge. Methodology/Principal Finding In the present study, we investigated the effects of a dose dependent treatment of mice with L. gasseri expressing the PA-DCpep fusion protein on intestinal and systemic immune responses and confirmed its safety. Treatment of mice with different doses of L. gasseri expressing PA-DCpep stimulated colonic immune responses, resulting in the activation of innate immune cells, including dendritic cells, which induced robust Th1, Th17, CD4+Foxp3+ and CD8+Foxp3+ T cell immune responses. Notably, high doses of L. gasseri expressing PA-DCpep (1012 CFU) were not toxic to the mice. Treatment of mice with L. gasseri expressing PA-DCpep triggered phenotypic maturation and the release of proinflammatory cytokines by dendritic cells and macrophages. Moreover, treatment of mice with L. gasseri expressing PA-DCpep enhanced antibody immune responses, including IgA, IgG1, IgG2b, IgG2c and IgG3. L. gasseri expressing PA-DCpep also increased the gene expression of numerous pattern recognition receptors, including Toll-like receptors, C-type lectin receptors and NOD-like receptors. Conclusion/Significance These findings suggest that L. gasseri expressing PA-DCpep has substantial immunopotentiating properties, as it can induce humoral and T cell-mediated immune responses upon oral administration and may be used as a safe oral vaccine against anthrax challenge. PMID:23383086

Vaccination of rhesus macaques with the live-attenuated HSV-1 vaccine VC2 stimulates the proliferation of mucosal T cells and germinal center responses resulting in sustained production of highly neutralizing antibodies.

PubMed

Stanfield, Brent A; Pahar, Bapi; Chouljenko, Vladimir N; Veazey, Ronald; Kousoulas, Konstantin G

2017-01-23

We have shown that the live-attenuated HSV-1 VC2 vaccine strain with mutations in glycoprotein K (gK) and the membrane protein UL20 is unable to establish latency in vaccinated animals and produces a robust immune response capable of completely protecting mice against lethal vaginal HSV-1 or HSV-2 infections. To better understand the immune response generated by vaccination with VC2, we tested its ability to elicit immune responses in rhesus macaques. Vaccinated animals showed no signs of disease and developed increasing HSV-1 and HSV-2 reactive IgG 1 after two booster vaccinations, while IgG subtypes IgG 2 and IgG 3 remained at low to undetectable levels. All vaccinated animals produced high levels of cross protective neutralizing antibodies. Flow cytometry analysis of cells isolated from draining lymph nodes showed that VC2 vaccination stimulated significant increases in plasmablast (CD27 high CD38 high ) and mature memory (CD21 - IgM - ) B cells. T cell analysis on cells isolated from draining lymph node biopsies demonstrated a statistically significant increase in proliferating (Ki67 + ) follicular T helper cells and regulatory CXCR5 + CD8 + cytotoxic T cells. Analysis of plasma isolated two weeks post vaccination showed significant increases in circulating CXCL13 indicating increased germinal center activity. Cells isolated from vaginal biopsy samples collected over the course of the study exhibited vaccination-dependent increases in proliferating (Ki67 + ) CD4 + and CD8 + T cell populations. These results suggest that intramuscular vaccination with the live-attenuated HSV-1 VC2 vaccine strain can stimulate robust IgG 1 antibody responses that persist for >250days post vaccination. In addition, vaccination lead to the maturation of B cells into plasmablast and mature memory B cells, the expansion of follicular T helper cells, and affects in the mucosal immune responses. These data suggest that the HSV VC2 vaccine induces potent immune responses that could help

Induction of complex immune responses and strong protection against retrovirus challenge by adenovirus-based immunization depends on the order of vaccine delivery.

PubMed

Kaulfuß, Meike; Wensing, Ina; Windmann, Sonja; Hrycak, Camilla Patrizia; Bayer, Wibke

2017-02-06

In the Friend retrovirus mouse model we developed potent adenovirus-based vaccines that were designed to induce either strong Friend virus GagL 85-93 -specific CD8 + T cell or antibody responses, respectively. To optimize the immunization outcome we evaluated vaccination strategies using combinations of these vaccines. While the vaccines on their own confer strong protection from a subsequent Friend virus challenge, the simple combination of the vaccines for the establishment of an optimized immunization protocol did not result in a further improvement of vaccine effectivity. We demonstrate that the co-immunization with GagL 85-93 /leader-gag encoding vectors together with envelope-encoding vectors abrogates the induction of GagL 85-93 -specific CD8 + T cells, and in successive immunization protocols the immunization with the GagL 85-93 /leader-gag encoding vector had to precede the immunization with an envelope encoding vector for the efficient induction of GagL 85-93 -specific CD8 + T cells. Importantly, the antibody response to envelope was in fact enhanced when the mice were adenovirus-experienced from a prior immunization, highlighting the expedience of this approach. To circumvent the immunosuppressive effect of envelope on immune responses to simultaneously or subsequently administered immunogens, we developed a two immunizations-based vaccination protocol that induces strong immune responses and confers robust protection of highly Friend virus-susceptible mice from a lethal Friend virus challenge.

Adjuvant-carrying synthetic vaccine particles augment the immune response to encapsulated antigen and exhibit strong local immune activation without inducing systemic cytokine release

PubMed Central

Ilyinskii, Petr O.; Roy, Christopher J.; O’Neil, Conlin P.; Browning, Erica A.; Pittet, Lynnelle A.; Altreuter, David H.; Alexis, Frank; Tonti, Elena; Shi, Jinjun; Basto, Pamela A.; Iannacone, Matteo; Radovic-Moreno, Aleksandar F.; Langer, Robert S.; Farokhzad, Omid C.; von Andrian, Ulrich H.; Johnston, Lloyd P.M.; Kishimoto, Takashi Kei

2014-01-01

Augmentation of immunogenicity can be achieved by particulate delivery of an antigen and by its co-administration with an adjuvant. However, many adjuvants initiate strong systemic inflammatory reactions in vivo, leading to potential adverse events and safety concerns. We have developed a synthetic vaccine particle (SVP) technology that enables co-encapsulation of antigen with potent adjuvants. We demonstrate that co-delivery of an antigen with a TLR7/8 or TLR9 agonist in synthetic polymer nanoparticles results in a strong augmentation of humoral and cellular immune responses with minimal systemic production of inflammatory cytokines. In contrast, antigen encapsulated into nanoparticles and admixed with free TLR7/8 agonist leads to lower immunogenicity and rapid induction of high levels of inflammatory cytokines in the serum (e.g., TNF-α and IL-6 levels are 50- to 200-fold higher upon injection of free resiquimod (R848) than of nanoparticle-encapsulated R848). Conversely, local immune stimulation as evidenced by cellular infiltration of draining lymph nodes and by intranodal cytokine production was more pronounced and persisted longer when SVP-encapsulated TLR agonists were used. The strong local immune activation achieved using a modular self-assembling nanoparticle platform markedly enhanced immunogenicity and was equally effective whether antigen and adjuvant were co-encapsulated in a single nanoparticle formulation or co-delivered in two separate nanoparticles. Moreover, particle encapsulation enabled the utilization of CpG oligonucleotides with the natural phosphodiester backbone, which are otherwise rapidly hydrolyzed by nucleases in vivo. The use of SVP may enable clinical use of potent TLR agonists as vaccine adjuvants for indications where cellular immunity or robust humoral responses are required. PMID:24593999

AF03-adjuvanted and non-adjuvanted pandemic influenza A (H1N1) 2009 vaccines induce strong antibody responses in seasonal influenza vaccine-primed and unprimed mice.

PubMed

Caillet, Catherine; Piras, Fabienne; Bernard, Marie-Clotilde; de Montfort, Aymeric; Boudet, Florence; Vogel, Frederick R; Hoffenbach, Agnès; Moste, Catherine; Kusters, Inca

2010-04-19

Pandemic influenza vaccines have been manufactured using the A/California/07/2009 (H1N1) strain as recommended by the World Health Organization. We evaluated in mice the immunogenicity of pandemic (H1N1) 2009 vaccine and the impact of prior vaccination against seasonal trivalent influenza vaccines (TIV) on antibody responses against pandemic (H1N1) 2009. In naïve mice, a single dose of unadjuvanted H1N1 vaccine (3 microg of HA) was shown to elicit hemagglutination inhibition (HI) antibody titers >40, a titer associated with protection in humans against seasonal influenza. A second vaccine dose of pandemic (H1N1) 2009 vaccine strongly increased these titers, which were consistently higher in mice previously primed with TIV than in naïve mice. At a low immunization dose (0.3 microg of HA), the AF03-adjuvanted vaccine elicited higher HI antibody titers than the corresponding unadjuvanted vaccines in both naïve and TIV-primed animals, suggesting a potential for antigen dose-sparing. These results are in accordance with the use in humans of a split-virion inactivated pandemic (H1N1) 2009 vaccine formulated with or without AF03 adjuvant to protect children and young adults against influenza A (H1N1) 2009 infection. Copyright 2010 Elsevier Ltd. All rights reserved.

Recent trends in vaccine delivery systems: A review

PubMed Central

Saroja, CH; Lakshmi, PK; Bhaskaran, Shyamala

2011-01-01

Vaccines are the preparations given to patients to evoke immune responses leading to the production of antibodies (humoral) or cell-mediated responses that will combat infectious agents or noninfectious conditions such as malignancies. Alarming safety profile of live vaccines, weak immunogenicity of sub-unit vaccines and immunization, failure due to poor patient compliance to booster doses which should potentiate prime doses are few strong reasons, which necessitated the development of new generation of prophylactic and therapeutic vaccines to promote effective immunization. Attempts are being made to deliver vaccines through carriers as they control the spatial and temporal presentation of antigens to immune system thus leading to their sustained release and targeting. Hence, lower doses of weak immunogens can be effectively directed to stimulate immune responses and eliminate the need for the administration of prime and booster doses as a part of conventional vaccination regimen. This paper reviews carrier systems such as liposomes, microspheres, nanoparticles, dendrimers, micellar systems, ISCOMs, plant-derived viruses which are now being investigated and developed as vaccine delivery systems. This paper also describes various aspects of “needle-free technologies” used to administer the vaccine delivery systems through different routes into the human body. PMID:23071924

Biologic Activity of Autologous, Granulocyte-Macrophage Colony Stimulating Factor Secreting Alveolar Soft Parts Sarcoma and Clear Cell Sarcoma Vaccines

PubMed Central

Goldberg, John; Fisher, David E.; Demetri, George D.; Neuberg, Donna; Allsop, Stephen A.; Fonseca, Catia; Nakazaki, Yukoh; Nemer, David; Raut, Chandrajit P.; George, Suzanne; Morgan, Jeffrey A.; Wagner, Andrew J.; Freeman, Gordon J.; Ritz, Jerome; Lezcano, Cecilia; Mihm, Martin; Canning, Christine; Hodi, F. Stephen; Dranoff, Glenn

2015-01-01

Purpose Alveolar soft parts sarcoma (ASPS) and clear cell sarcoma (CCS) are rare mesenchymal malignancies driven by chromosomal translocations that activate members of the microphthalmia transcription factor (MITF) family. However, in contrast to malignant melanoma, little is known about their immunogenicity. To learn more about the host response to ASPS and CCS, we conducted a phase I clinical trial of vaccination with irradiated, autologous sarcoma cells engineered by adenoviral mediated gene transfer to secrete granulocyte-macrophage colony stimulating factor (GM-CSF). Experimental Design Metastatic tumors from ASPS and CCS patients were resected, processed to single cell suspensions, transduced with a replication defective adenoviral vector encoding GM-CSF, and irradiated. Immunizations were administered subcutaneously and intradermally weekly times three and then every other week. Results Vaccines were successfully manufactured for 11 of the 12 enrolled patients. Eleven subjects received from 3 to 13 immunizations. Toxicities were restricted to grade 1–2 skin reactions at inoculation sites. Vaccination elicited local dendritic cell infiltrates and stimulated T cell mediated delayed type-hypersensitivity reactions to irradiated, autologous tumor cells. Antibody responses to tissue-type plasminogen activator (tTPA) and angiopoietins-1/2 were detected. Tumor biopsies showed programmed death-1 (PD-1) positive CD8+ T cells in association with PD ligand-1 (PD-L1) expressing sarcoma cells. No tumor regressions were observed. Conclusions Vaccination with irradiated, GM-CSF secreting autologous sarcoma cell vaccines is feasible, safe, and biologically active. Concurrent targeting of angiogenic cytokines and antagonism of the PD-1 negative regulatory pathway might intensify immune-mediated tumor destruction. PMID:25805798

Universal Vaccines and Vaccine Platforms to Protect against Influenza Viruses in Humans and Agriculture

PubMed Central

Rajão, Daniela S.; Pérez, Daniel R.

2018-01-01

Influenza virus infections pose a significant threat to public health due to annual seasonal epidemics and occasional pandemics. Influenza is also associated with significant economic losses in animal production. The most effective way to prevent influenza infections is through vaccination. Current vaccine programs rely heavily on the vaccine's ability to stimulate neutralizing antibody responses to the hemagglutinin (HA) protein. One of the biggest challenges to an effective vaccination program lies on the fact that influenza viruses are ever-changing, leading to antigenic drift that results in escape from earlier immune responses. Efforts toward overcoming these challenges aim at improving the strength and/or breadth of the immune response. Novel vaccine technologies, the so-called universal vaccines, focus on stimulating better cross-protection against many or all influenza strains. However, vaccine platforms or manufacturing technologies being tested to improve vaccine efficacy are heterogeneous between different species and/or either tailored for epidemic or pandemic influenza. Here, we discuss current vaccines to protect humans and animals against influenza, highlighting challenges faced to effective and uniform novel vaccination strategies and approaches. PMID:29467737

A fusion protein of HCMV IE1 exon4 and IE2 exon5 stimulates potent cellular immunity in an MVA vaccine vector

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

Wang, Z.; Zhou, W.; Srivastava, T.

2008-08-01

A therapeutic CMV vaccine incorporating an antigenic repertoire capable of eliciting a cellular immune response has yet to be successfully implemented for patients who already have acquired an infection. To address this problem, we have developed a vaccine candidate derived from modified vaccinia Ankara (MVA) that expresses three immunodominant antigens (pp65, IE1, IE2) from CMV. The novelty of this vaccine is the fusion of two adjacent exons from the immediate-early region of CMV, their successful expression in MVA, and robust immunogenicity in both primary and memory response models. Evaluation of the immunogenicity of the viral vaccine in mouse models showsmore » that it can stimulate primary immunity against all three antigens in both the CD4{sup +} and CD8{sup +} T cell subsets. Evaluation of human PBMC from healthy CMV-positive donors or patients within 6 months of receiving hematopoietic cell transplant shows robust stimulation of existing CMV-specific CD4{sup +} and CD8{sup +} T cell subsets.« less

Human papillomavirus vaccination of males: attitudes and perceptions of physicians who vaccinate females.

PubMed

Weiss, Thomas W; Zimet, Gregory D; Rosenthal, Susan L; Brenneman, Susan K; Klein, Jonathan D

2010-07-01

We assessed U.S. physicians' attitudes and perceptions regarding potential human papillomavirus (HPV) vaccination of males. We surveyed a random sample of 2,714 pediatricians and family practitioners identified in administrative claims of a U.S. health plan as HPV vaccinators of females; 595 pediatricians and 499 family practitioners participated. Most physicians would recommend HPV vaccination to males aged 11-12 (63.9%), 13-18 (93.4%), and 19-26 (92.7%) years. Physicians agreed that males should be vaccinated to prevent them from getting genital and anal warts (52.9% strongly and 36.0% somewhat) and to protect females from cervical cancer (75.3% strongly and 20.8% somewhat). Physicians agreed that an HPV vaccine recommendation for males would increase opportunities to discuss sexual health with adolescent male patients (58.7% strongly, 35.3% somewhat). Most did not strongly agree (15.4% strongly, 45.4% somewhat) that parents of adolescent male patients would be interested in HPV vaccination for males, that a gender-neutral HPV vaccine recommendation would increase acceptance by adolescent females and their parents (19.6% strongly, 42.0% somewhat), or that a gender-neutral recommendation would improve current female vaccination rates (10.4% strongly, 26.0% somewhat). Physicians who currently vaccinate females against HPV supported the concept of vaccinating males for its benefits for both sexes. They agreed that a gender-neutral HPV vaccination recommendation would be appropriate with regard to public health and believed that it would increase opportunities for sexual health discussions, but were less sure that such a recommendation would change patient or parental attitudes toward HPV vaccination or improve current HPV vaccination efforts. Copyright (c) 2010 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Induction of IL-21 in Peripheral T Follicular Helper cells is Indicator of Influenza Vaccine Response in Previously Vaccinated HIV-Infected Pediatric Cohort

PubMed Central

de Armas, Lesley R.; Cotugno, Nicola; Pallikkuth, Suresh; Pan, Li; Rinaldi, Stefano; Sanchez, M. Celeste; Gonzalez, Louis; Cagigi, Alberto; Rossi, Paolo; Palma, Paolo; Pahwa, Savita

2016-01-01

HIV-infected patients of all ages frequently underperform in responsiveness to seasonal influenza vaccination despite virologic control of HIV. Molecular mechanisms governing this impairment as well as predictive biomarkers for responsiveness remain unknown. This study was performed in pre-vaccination samples (T0) of HIV-infected children who received the 2012–2013 seasonal influenza vaccine. Response status was determined based on established criteria of hemagglutination inhibition (HAI) titer; participants with HAI ≥ 1:40 plus ≥ 4-fold increase over T0 at three weeks post-vaccination (T1) were designated as responders. All children had a history of prior influenza vaccinations. At T0, frequencies of CD4 T cell subsets, including peripheral T follicular helper (pTfh) cells which provide help to B cells for developing into Ab secreting cells were similar between responders and non-responders. However, in response to in vitro stimulation with H1N1 antigen, differential gene expression related to pTfh function was observed by Fluidigm high density RT-PCR between responders and non-responders. In responders, H1N1 stimulation at pre-vaccination also resulted in CXCR5 induction (mRNA and protein) in CD4 T cells and IL21 gene induction in pTfh cells that strongly associated with H1N1-specific B cell responses post-vaccination. In contrast, CD4 T cells of non-responders exhibited increased expression of IL2 and STAT5 genes which are known to antagonize pTfh function. These results suggest that the quality of pTfh at the time of immunization are important for influenza vaccine responses and provide a rationale for targeted, ex vivo antigen-driven molecular profiling of purified immune cells to detect predictive biomarkers of vaccine response. PMID:28130496

PLGA particulate subunit tuberculosis vaccines promote humoral and Th17 responses but do not enhance control of Mycobacterium tuberculosis infection

PubMed Central

Parumasivam, Thaigarajan; Chan, John Gar Yan; Lin, Leon C. W.; Flórido, Manuela; West, Nicholas P.; Chan, Hak-Kim; Britton, Warwick J.

2018-01-01

Tuberculosis places a staggering burden on human health globally. The new World Health Organisation End-TB Strategy has highlighted the urgent need for more effective TB vaccines to improve control of the disease. Protein-based subunit vaccines offer potential as safe and effective generators of protective immunity, and the use of particulate vaccine formulation and delivery by the pulmonary route may enhance local immunogenicity. In this study, novel particulate subunit vaccines were developed utilising biodegradable poly(lactic-co-glycolic acid) (PLGA) slow-release particles as carriers for the Mycobacterium tuberculosis lipoprotein MPT83, together with the adjuvants trehalose-dibehenate (TDB) or Monophosphoryl lipid A (MPL). Following delivery by the pulmonary or subcutaneous routes, the immunogenicity and protective efficacy of these vaccines were assessed in a murine model of M. tuberculosis infection. When delivered peripherally, these vaccines induced modest, antigen-specific Th1 and Th17 responses, but strong anti-MPT83 antibody responses. Mucosal delivery of the PLGA(MPT83) vaccine, with or without TDB, increased antigen-specific Th17 responses in the lungs, however, PLGA-encapsulated vaccines did not provide protection against M. tuberculosis challenge. By contrast, peripheral delivery of DDA liposomes containing MPT83 and TDB or MPL, stimulated both Th1 and Th17 responses and generated protection against M. tuberculosis challenge. Therefore, PLGA-formulated vaccines primarily stimulate strong humoral immunity, or Th17 responses if used mucosally, and may be a suitable carrier for vaccines against extracellular pathogens. This study emphasises the critical nature of the vaccine carrier, adjuvant and route of delivery for optimising vaccine efficacy against TB. PMID:29554138

A multi-subunit Chlamydia vaccine inducing neutralizing antibodies and strong IFN-γ+ CMI responses protects against a genital infection in minipigs

PubMed Central

Bøje, Sarah; Olsen, Anja Weinreich; Erneholm, Karin; Agerholm, Jørgen Steen; Jungersen, Gregers; Andersen, Peter; Follmann, Frank

2016-01-01

Chlamydia is the most widespread sexually transmitted bacterial disease and a prophylactic vaccine is highly needed. Ideally, this vaccine is required to induce a combined response of Th1 cell-mediated immune (CMI) response in concert with neutralizing antibodies. Using a novel Göttingen minipig animal model, we evaluated the immunogenicity and efficacy of a multi-subunit vaccine formulated in the strong Th1-inducing adjuvant CAF01. We evaluated a mixture of two fusion proteins (Hirep1 and CTH93) designed to promote either neutralizing antibodies or cell-mediated immunity, respectively. Hirep1 is a novel immunogen based on the variant domain (VD) 4 region from major outer membrane protein (MOMP) serovar (Sv) D, SvE and SvF, and CTH93 is a fusion molecule of three antigens (CT043, CT414 and MOMP). Pigs were immunized twice intramuscularly with either Hirep1+CTH93/CAF01, UV-inactivated Chlamydia trachomatis SvD bacteria (UV-SvD/CAF01) or CAF01. The Hirep1+CTH93/CAF01 vaccine induced a strong CMI response against the vaccine antigens and high titers of antibodies, particularly against the VD4 region of MOMP. Sera from Hirep1+CTH93/CAF01 immunized pigs neutralized C. trachomatis SvD and SvF infectivity in vitro. Both Hirep1+CTH93/CAF01 and UV-SvD/CAF01 vaccination protected pigs against a vaginal C. trachomatis SvD infection. In conclusion, the Hirep1+CTH93/CAF01 vaccine proved highly immunogenic and equally protective as UV-SvD/CAF01 showing promise for the development of a subunit vaccine against Chlamydia. PMID:26268662

Live attenuated measles vaccine expressing HIV-1 Gag virus like particles covered with gp160DELTAV1V2 is strongly immunogenic

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

Guerbois, Mathilde; Moris, Arnaud; Combredet, Chantal

Although a live attenuated HIV vaccine is not currently considered for safety reasons, a strategy inducing both T cells and neutralizing antibodies to native assembled HIV-1 particles expressed by a replicating virus might mimic the advantageous characteristics of live attenuated vaccine. To this aim, we generated a live attenuated recombinant measles vaccine expressing HIV-1 Gag virus-like particles (VLPs) covered with gp160DELTAV1V2 Env protein. The measles-HIV virus replicated efficiently in cell culture and induced the intense budding of HIV particles covered with Env. In mice sensitive to MV infection, this recombinant vaccine stimulated high levels of cellular and humoral immunity tomore » both MV and HIV with neutralizing activity. The measles-HIV virus infected human professional antigen-presenting cells, such as dendritic cells and B cells, and induced efficient presentation of HIV-1 epitopes and subsequent activation of human HIV-1 Gag-specific T cell clones. This candidate vaccine will be next tested in non-human primates. As a pediatric vaccine, it might protect children and adolescents simultaneously from measles and HIV.« less

Bioactivity of Autologous Irradiated Renal Cell Carcinoma Vaccines Generated by ex Vivo Granulocyte-Macrophage Colony-stimulating Factor Gene Transfer1

PubMed Central

Simons, Jonathan W.; Jaffee, Elizabeth M.; Weber, Christine E.; Levitsky, Hyam I.; Nelson, William G.; Carducci, Michael A.; Lazenby, Audrey J.; Cohen, Lawrence K.; Finn, Christy C.; Clift, Shirley M.; Hauda, Karen M.; Beck, Lisa A.; Leiferman, Kristen M.; Owens, Albert H.; Piantadosi, Steven; Dranoff, Glenn; Mulligan, Richard C.; Pardoll, Drew M.; Marshall, Fray F.

2014-01-01

Granulocyte-macrophage colony-stimulating factor (GM-CSF) gene-transduced, irradiated tumor vaccines induce potent, T-cell-mediated antitumor immune responses in preclinical models. We report the initial results of a Phase I trial evaluating this strategy for safety and the induction of immune responses in patients with metastatic renal cell carcinoma (RCC). Patients were treated in a randomized, double-blind dose-escalation study with equivalent doses of autologous, irradiated RCC vaccine cells with or without ex vivo human GM-CSF gene transfer. The replication-defective retroviral vector MFG was used for GM-CSF gene transfer. No dose-limiting toxicities were encountered in 16 fully evaluable patients. GM-CSF gene-transduced vaccines were equivalent in toxicity to nontransduced vaccines up to the feasible limits of autologous tumor vaccine yield. No evidence of autoimmune disease was observed. Biopsies of intradermal sites of injection with GM-CSF gene-transduced vaccines contained distinctive macrophage, dendritic cell, eosinophil, neutrophil, and T-cell infiltrates similar to those observed in preclinical models of efficacy. Histological analysis of delayed-type hypersensitivity responses in patients vaccinated with GM-CSF-transduced vaccines demonstrated an intense eosinophil infiltrate that was not observed in patients who received nontransduced vaccines. An objective partial response was observed in a patient treated with GM-CSF gene-transduced vaccine who displayed the largest delayed-type hypersensitivity conversion. No replication-competent retrovirus was detected in vaccinated patients. This Phase I study demonstrated the feasibility, safety, and bioactivity of an autologous GM-CSF gene-transduced tumor vaccine for RCC patients. PMID:9108457

Exploiting fungal cell wall components in vaccines.

PubMed

Levitz, Stuart M; Huang, Haibin; Ostroff, Gary R; Specht, Charles A

2015-03-01

Innate recognition of fungi leads to strong adaptive immunity. Investigators are trying to exploit this observation in vaccine development by combining antigens with evolutionarily conserved fungal cell wall carbohydrates to induce protective responses. Best studied is β-1,3-glucan, a glycan that activates complement and is recognized by dectin-1. Administration of antigens in association with β-1,3-glucan, either by direct conjugation or complexed in glucan particles, results in robust humoral and cellular immune responses. While the host has a host of mannose receptors, responses to fungal mannoproteins generally are amplified if cells are cooperatively stimulated with an additional danger signal such as a toll-like receptor agonist. Chitosan, a polycationic homopolymer of glucosamine manufactured by the deacetylation of chitin, is being studied as an adjuvant in DNA and protein-based vaccines. It appears particularly promising in mucosal vaccines. Finally, universal and organism-specific fungal vaccines have been formulated by conjugating fungal cell wall glycans to carrier proteins. A major challenge will be to advance these experimental findings so that at risk patients can be protected.

Exploiting fungal cell wall components in vaccines

PubMed Central

Levitz, Stuart M.; Huang, Haibin; Ostroff, Gary R.; Specht, Charles A.

2014-01-01

Innate recognition of fungi leads to strong adaptive immunity. Investigators are trying to exploit this observation in vaccine development by combining antigens with evolutionarily conserved fungal cell wall carbohydrates to induce protective responses. Best studied is β-1,3-glucan, a glycan that activates complement and is recognized by Dectin-1. Administration of antigens in association with β-1,3-glucan, either by direct conjugation or complexed in glucan particles, results in robust humoral and cellular immune responses. While the host has a host of mannose receptors, responses to fungal mannoproteins generally are amplified if cells are cooperatively stimulated with an additional danger signal such as a toll-like receptor agonist. Chitosan, a polycationic homopolymer of glucosamine manufactured by the deacetylation of chitin, is being studied as an adjuvant in DNA and protein-based vaccines. It appears particularly promising in mucosal vaccines. Finally, universal and organism-specific fungal vaccines have been formulated by conjugating fungal cell wall glycans to carrier proteins. A major challenge will be to advance these experimental findings so that at risk patients can be protected. PMID:25404118

Preclinical evaluation of bacterially produced RSV-G protein vaccine: Strong protection against RSV challenge in cotton rat model.

PubMed

Fuentes, Sandra; Klenow, Laura; Golding, Hana; Khurana, Surender

2017-02-10

In current study, we evaluated the safety and protective efficacy of recombinant unglycosylated RSV G protein ectodomain produced in E. coli (in presence and absence of oil-in-water adjuvant) in a preclinical RSV susceptible cotton rat challenge model compared to formaldehyde inactivated RSV (FI-RSV) and live RSV experimental infection. The adjuvanted G protein vaccine induced robust neutralization antibody responses comparable to those generated by live RSV infection. Importantly, adjuvanted G protein significantly reduced viral loads in both the lungs and nose at early time points following viral challenge. Antibody kinetics determined by Surface Plasmon Resonance showed that adjuvanted G generated 10-fold higher G-binding antibodies compared to non-adjvuanted G vaccine and live RSV infection, which correlated strongly with both neutralization titers and viral load titers in the nose and lungs post-viral challenge. Antibody diversity analysis revealed immunodominant antigenic sites in the N- and C-termini of the RSV-G protein, that were boosted >10-fold by adjuvant and inversely correlated with viral load titers. Enhanced lung pathology was observed only in animals vaccinated with FI-RSV, but not in animals vaccinated with unadjuvanted or adjuvanted RSV-G vaccine after viral challenge. The bacterially produced unglycosylated G protein could be developed as a protective vaccine against RSV disease.

Preclinical evaluation of bacterially produced RSV-G protein vaccine: Strong protection against RSV challenge in cotton rat model

PubMed Central

Fuentes, Sandra; Klenow, Laura; Golding, Hana; Khurana, Surender

2017-01-01

In current study, we evaluated the safety and protective efficacy of recombinant unglycosylated RSV G protein ectodomain produced in E. coli (in presence and absence of oil-in-water adjuvant) in a preclinical RSV susceptible cotton rat challenge model compared to formaldehyde inactivated RSV (FI-RSV) and live RSV experimental infection. The adjuvanted G protein vaccine induced robust neutralization antibody responses comparable to those generated by live RSV infection. Importantly, adjuvanted G protein significantly reduced viral loads in both the lungs and nose at early time points following viral challenge. Antibody kinetics determined by Surface Plasmon Resonance showed that adjuvanted G generated 10-fold higher G-binding antibodies compared to non-adjvuanted G vaccine and live RSV infection, which correlated strongly with both neutralization titers and viral load titers in the nose and lungs post-viral challenge. Antibody diversity analysis revealed immunodominant antigenic sites in the N- and C-termini of the RSV-G protein, that were boosted >10-fold by adjuvant and inversely correlated with viral load titers. Enhanced lung pathology was observed only in animals vaccinated with FI-RSV, but not in animals vaccinated with unadjuvanted or adjuvanted RSV-G vaccine after viral challenge. The bacterially produced unglycosylated G protein could be developed as a protective vaccine against RSV disease. PMID:28186208

Peptide vaccines prevent tumor growth by activating T cells that respond to native tumor antigens.

PubMed

Jordan, Kimberly R; McMahan, Rachel H; Kemmler, Charles B; Kappler, John W; Slansky, Jill E

2010-03-09

Peptide vaccines enhance the response of T cells toward tumor antigens and represent a strategy to augment antigen-independent immunotherapies of cancer. However, peptide vaccines that include native tumor antigens rarely prevent tumor growth. We have assembled a set of peptide variants for a mouse-colon tumor model to determine how to improve T-cell responses. These peptides have similar affinity for MHC molecules, but differ in the affinity of the peptide-MHC/T-cell receptor interaction with a tumor-specific T-cell clone. We systematically demonstrated that effective antitumor responses are generated after vaccination with variant peptides that stimulate the largest proportion of endogenous T cells specific for the native tumor antigen. Importantly, we found some variant peptides that strongly stimulated a specific T-cell clone in vitro, but elicited fewer tumor-specific T cells in vivo, and were not protective. The T cells expanded by the effective vaccines responded to the wild-type antigen by making cytokines and killing target cells, whereas most of the T cells expanded by the ineffective vaccines only responded to the peptide variants. We conclude that peptide-variant vaccines are most effective when the peptides react with a large responsive part of the tumor-specific T-cell repertoire.

An endogenous immune adjuvant released by necrotic cells for enhancement of DNA vaccine potency.

PubMed

Dorostkar, Rohollah; Bamdad, Taravat; Parsania, Masoud; Pouriayevali, Hassan

2012-12-01

Improving vaccine potency in the induction of a strong cell-mediated cytotoxicity can enhance the efficacy of vaccines. Necrotic cells and the supernatant of necrotic tumor cells are attractive adjuvants, on account of their ability to recruit antigen-presenting cells to the site of antigen synthesis as well as its ability to stimulate the maturation of dendritic cells. To evaluate the utility of supernatant of necrotic tumor cells as a DNA vaccine adjuvant in a murine model. The supernatant of EL4 necrotic cells was co-administered with a DNA vaccine expressing the glycoprotein B of Herpes simplex virus-1 as an antigen model under the control of Cytomegalovirus promoter. C57BL/6 mice were vaccinated three times at two weeks intervals with glycoprotein B DNA vaccine and supernatant of necrotic EL4 cells. Five days after the last immunization, cell cytotoxicity, IFN-γ and IL-4 were evaluated. The obtained data showed that the production of IFN-γ from the splenocytes after antigenic stimulation in the presence of the supernatant of necrotic EL4 cells was significantly higher than the other groups (p<0.002). The flow cytometry results showed a significant increase in the apoptosis/necrosis of EL4 cells in the mice immunized with DNA vaccine and supernatant of necrotic EL4 cells comparing to the other groups (p<0.001). The supernatant of necrotic cells contains adjuvant properties that can be considered as a candidate for tumor vaccination.

Chimeric Vaccine Stimulation of Human Dendritic Cell Indoleamine 2, 3-Dioxygenase Occurs via the Non-Canonical NF-κB Pathway

PubMed Central

Kim, Nan-Sun; Mbongue, Jacques C.; Nicholas, Dequina A.; Esebanmen, Grace E.; Unternaehrer, Juli J.; Firek, Anthony F.; Langridge, William H. R.

2016-01-01

A chimeric protein vaccine composed of the cholera toxin B subunit fused to proinsulin (CTB-INS) was shown to suppress type 1 diabetes onset in NOD mice and upregulate biosynthesis of the tryptophan catabolic enzyme indoleamine 2, 3-dioxygenase (IDO1) in human dendritic cells (DCs). Here we demonstrate siRNA inhibition of the NF-κB-inducing kinase (NIK) suppresses vaccine-induced IDO1 biosynthesis as well as IKKα phosphorylation. Chromatin immunoprecipitation (ChIP) analysis of CTB-INS inoculated DCs showed that RelB bound to NF-κB consensus sequences in the IDO1 promoter, suggesting vaccine stimulation of the non-canonical NF-κB pathway activates IDO1 expression in vivo. The addition of Tumor Necrosis Factor Associated Factors (TRAF) TRAF 2, 3 and TRAF6 blocking peptides to vaccine inoculated DCs was shown to inhibit IDO1 biosynthesis. This experimental outcome suggests vaccine activation of the TNFR super-family receptor pathway leads to upregulation of IDO1 biosynthesis in CTB-INS inoculated dendritic cells. Together, our experimental data suggest the CTB-INS vaccine uses a TNFR-dependent signaling pathway of the non-canonical NF-κB signaling pathway resulting in suppression of dendritic cell mediated type 1 diabetes autoimmunity. PMID:26881431

Nasal Vaccination Stimulates CD8+ T Cells for Potent Protection Against Mucosal Brucella melitensis Challenge

PubMed Central

Clapp, Beata; Yang, Xinghong; Thornburg, Theresa; Walters, Nancy; Pascual, David W.

2016-01-01

Brucellosis remains a significant zoonotic threat worldwide. Humans and animals acquire infection via their oropharynx and upper respiratory tract following oral or aerosol exposure. After mucosal infection, brucellosis develops into a systemic disease. Mucosal vaccination could offer a viable alternative to conventional injection practices to deter disease. Using a nasal vaccination approach, the ΔznuA B. melitensis was found to confer potent protection against pulmonary Brucella challenge, and reduce colonization of spleens and lungs by more than 2500-fold, with more than 50% of vaccinated mice showing no detectable brucellae. Furthermore, tenfold more brucellae-specific, IFN-γ-producing CD8+ T cells than CD4+ T cells were induced in the spleen and respiratory lymph nodes. Evaluation of pulmonary and splenic CD8+ T cells from mice vaccinated with ΔznuA B. melitensis revealed that these expressed an activated effector memory (CD44hiCD62LloCCR7lo) T cells producing elevated levels of IFN-γ, TNF-α, perforin, and granzyme B. To assess the relative importance of these increased numbers of CD8+ T cells, CD8−/− mice were challenged with virulent B. melitensis, and they showed markedly increased bacterial loads in organs in contrast to similarly challenged CD4−/− mice. Only ΔznuA B. melitensis- and Rev-1-vaccinated CD4−/− and wild-type mice, not CD8−/− mice, were completely protected against Brucella challenge. Determination of cytokines responsible for conferring protection showed the relative importance of IFN-γ, but not IL-17. Unlike wild-type mice, IL-17 was greatly induced in IFN-γ−/− mice, but IL-17 could not substitute for IFN-γ’s protection, although an increase in brucellae dissemination was observed upon in vivo IL-17 neutralization. These results show that nasal ΔznuA B. melitensis vaccination represents an attractive means to stimulate systemic and mucosal immune protection via CD8+ T cell engagement. PMID:26752510

Identification of immune factors regulating antitumor immunity using polymeric vaccines with multiple adjuvants.

PubMed

Ali, Omar A; Verbeke, Catia; Johnson, Chris; Sands, R Warren; Lewin, Sarah A; White, Des; Doherty, Edward; Dranoff, Glenn; Mooney, David J

2014-03-15

The innate cellular and molecular components required to mediate effective vaccination against weak tumor-associated antigens remain unclear. In this study, we used polymeric cancer vaccines incorporating different classes of adjuvants to induce tumor protection, to identify dendritic cell (DC) subsets and cytokines critical to this efficacy. Three-dimensional, porous polymer matrices loaded with tumor lysates and presenting distinct combinations of granulocyte macrophage colony-stimulating factor (GM-CSF) and various Toll-like receptor (TLR) agonists affected 70% to 90% prophylactic tumor protection in B16-F10 melanoma models. In aggressive, therapeutic B16 models, the vaccine systems incorporating GM-CSF in combination with P(I:C) or CpG-ODN induced the complete regression of solid tumors (≤40 mm(2)), resulting in 33% long-term survival. Regression analysis revealed that the numbers of vaccine-resident CD8(+) DCs, plasmacytoid DCs (pDC), along with local interleukin (IL)-12, and granulocyte colony-stimulating factor (G-CSF) concentrations correlated strongly to vaccine efficacy regardless of adjuvant type. Furthermore, vaccine studies in Batf3(-/-) mice revealed that CD8(+) DCs are required to affect tumor protection, as vaccines in these mice were deficient in cytotoxic T lymphocytes priming and IL-12 induction in comparison with wild-type. These studies broadly demonstrate that three-dimensional polymeric vaccines provide a potent platform for prophylactic and therapeutic protection, and can be used as a tool to identify critical components of a desired immune response. Specifically, these results suggest that CD8(+) DCs, pDCs, IL-12, and G-CSF play important roles in priming effective antitumor responses with these vaccines. ©2014 AACR.

A multi-subunit Chlamydia vaccine inducing neutralizing antibodies and strong IFN-γ⁺ CMI responses protects against a genital infection in minipigs.

PubMed

Bøje, Sarah; Olsen, Anja Weinreich; Erneholm, Karin; Agerholm, Jørgen Steen; Jungersen, Gregers; Andersen, Peter; Follmann, Frank

2016-02-01

Chlamydia is the most widespread sexually transmitted bacterial disease and a prophylactic vaccine is highly needed. Ideally, this vaccine is required to induce a combined response of Th1 cell-mediated immune (CMI) response in concert with neutralizing antibodies. Using a novel Göttingen minipig animal model, we evaluated the immunogenicity and efficacy of a multi-subunit vaccine formulated in the strong Th1-inducing adjuvant CAF01. We evaluated a mixture of two fusion proteins (Hirep1 and CTH93) designed to promote either neutralizing antibodies or cell-mediated immunity, respectively. Hirep1 is a novel immunogen based on the variant domain (VD) 4 region from major outer membrane protein (MOMP) serovar (Sv) D, SvE and SvF, and CTH93 is a fusion molecule of three antigens (CT043, CT414 and MOMP). Pigs were immunized twice intramuscularly with either Hirep1+CTH93/CAF01, UV-inactivated Chlamydia trachomatis SvD bacteria (UV-SvD/CAF01) or CAF01. The Hirep1+CTH93/CAF01 vaccine induced a strong CMI response against the vaccine antigens and high titers of antibodies, particularly against the VD4 region of MOMP. Sera from Hirep1+CTH93/CAF01 immunized pigs neutralized C. trachomatis SvD and SvF infectivity in vitro. Both Hirep1+CTH93/CAF01 and UV-SvD/CAF01 vaccination protected pigs against a vaginal C. trachomatis SvD infection. In conclusion, the Hirep1+CTH93/CAF01 vaccine proved highly immunogenic and equally protective as UV-SvD/CAF01 showing promise for the development of a subunit vaccine against Chlamydia.

Intramuscular Immunization of Mice with the Live-Attenuated Herpes Simplex Virus 1 Vaccine Strain VC2 Expressing Equine Herpesvirus 1 (EHV-1) Glycoprotein D Generates Anti-EHV-1 Immune Responses in Mice.

PubMed

Liu, Shiliang A; Stanfield, Brent A; Chouljenko, Vladimir N; Naidu, Shan; Langohr, Ingeborg; Del Piero, Fabio; Ferracone, Jacqueline; Roy, Alma A; Kousoulas, Konstantin G

2017-06-15

Vaccination remains the best option to combat equine herpesvirus 1 (EHV-1) infection, and several different strategies of vaccination have been investigated and developed over the past few decades. Herein, we report that the live-attenuated herpes simplex virus 1 (HSV-1) VC2 vaccine strain, which has been shown to be unable to enter into neurons and establish latency in mice, can be utilized as a vector for the heterologous expression of EHV-1 glycoprotein D (gD) and that the intramuscular immunization of mice results in strong antiviral humoral and cellular immune responses. The VC2-EHV-1-gD recombinant virus was constructed by inserting an EHV-1 gD expression cassette under the control of the cytomegalovirus immediate early promoter into the VC2 vector in place of the HSV-1 thymidine kinase (UL23) gene. The vaccines were introduced into mice through intramuscular injection. Vaccination with both the VC2-EHV-1-gD vaccine and the commercially available vaccine Vetera EHV XP 1/4 (Vetera; Boehringer Ingelheim Vetmedica) resulted in the production of neutralizing antibodies, the levels of which were significantly higher in comparison to those in VC2- and mock-vaccinated animals ( P < 0.01 or P < 0.001). Analysis of EHV-1-reactive IgG subtypes demonstrated that vaccination with the VC2-EHV-1-gD vaccine stimulated robust IgG1 and IgG2a antibodies after three vaccinations ( P < 0.001). Interestingly, Vetera-vaccinated mice produced significantly higher levels of IgM than mice in the other groups before and after challenge ( P < 0.01 or P < 0.05). Vaccination with VC2-EHV-1-gD stimulated strong cellular immune responses, characterized by the upregulation of both interferon- and tumor necrosis factor-positive CD4 + T cells and CD8 + T cells. Overall, the data suggest that the HSV-1 VC2 vaccine strain may be used as a viral vector for the vaccination of horses as well as, potentially, for the vaccination of other economically important animals. IMPORTANCE A novel virus

Apoptosis and other immune biomarkers predict influenza vaccine responsiveness.

PubMed

Furman, David; Jojic, Vladimir; Kidd, Brian; Shen-Orr, Shai; Price, Jordan; Jarrell, Justin; Tse, Tiffany; Huang, Huang; Lund, Peder; Maecker, Holden T; Utz, Paul J; Dekker, Cornelia L; Koller, Daphne; Davis, Mark M

2013-04-16

Despite the importance of the immune system in many diseases, there are currently no objective benchmarks of immunological health. In an effort to identifying such markers, we used influenza vaccination in 30 young (20-30 years) and 59 older subjects (60 to >89 years) as models for strong and weak immune responses, respectively, and assayed their serological responses to influenza strains as well as a wide variety of other parameters, including gene expression, antibodies to hemagglutinin peptides, serum cytokines, cell subset phenotypes and in vitro cytokine stimulation. Using machine learning, we identified nine variables that predict the antibody response with 84% accuracy. Two of these variables are involved in apoptosis, which positively associated with the response to vaccination and was confirmed to be a contributor to vaccine responsiveness in mice. The identification of these biomarkers provides new insights into what immune features may be most important for immune health.

Traditional and New Influenza Vaccines

PubMed Central

Wong, Sook-San

2013-01-01

SUMMARY The challenges in successful vaccination against influenza using conventional approaches lie in their variable efficacy in different age populations, the antigenic variability of the circulating virus, and the production and manufacturing limitations to ensure safe, timely, and adequate supply of vaccine. The conventional influenza vaccine platform is based on stimulating immunity against the major neutralizing antibody target, hemagglutinin (HA), by virus attenuation or inactivation. Improvements to this conventional system have focused primarily on improving production and immunogenicity. Cell culture, reverse genetics, and baculovirus expression technology allow for safe and scalable production, while adjuvants, dose variation, and alternate routes of delivery aim to improve vaccine immunogenicity. Fundamentally different approaches that are currently under development hope to signal new generations of influenza vaccines. Such approaches target nonvariable regions of antigenic proteins, with the idea of stimulating cross-protective antibodies and thus creating a “universal” influenza vaccine. While such approaches have obvious benefits, there are many hurdles yet to clear. Here, we discuss the process and challenges of the current influenza vaccine platform as well as new approaches that are being investigated based on the same antigenic target and newer technologies based on different antigenic targets. PMID:23824369

Improving birth dose coverage of hepatitis B vaccine.

PubMed Central

Hipgrave, David B.; Maynard, James E.; Biggs, Beverley-Ann

2006-01-01

Administration of a birth dose of hepatitis B vaccine (HepB vaccine) to neonates is recommended to prevent mother-to-infant transmission and chronic infection with the hepatitis B virus (HBV). Although manufacturers recommend HepB vaccine distribution and storage at 2-8 degrees C, recognition of the heat stability of hepatitis B surface antigen stimulated research into its use after storage at, or exposure to, ambient or high temperatures. Storage of HepB vaccine at ambient temperatures would enable birth dosing for neonates delivered at home in remote areas or at health posts lacking refrigeration. This article reviews the current evidence on the thermostability of HepB vaccine when stored outside the cold chain (OCC). The reports reviewed show that the vaccines studied were safe and effective whether stored cold or OCC. Field and laboratory data also verifies the retained potency of the vaccine after exposure to heat. The attachment of a highly stable variety of a vaccine vial monitor (measuring cumulative exposure to heat) on many HepB vaccines strongly supports policies allowing their storage OCC, when this will benefit birth dose coverage. We recommend that this strategy be introduced to improve birth dose coverage, especially in rural and remote areas. Concurrent monitoring and evaluation should be undertaken to affirm the safe implementation of this strategy, and assess its cost, feasibility and effect on reducing HBV infection rates. Meanwhile, release of manufacturer data verifying the potency of currently available HepB vaccines after exposure to heat will increase confidence in the use of vaccine vial monitors as a managerial tool during storage of HepB vaccine OCC. PMID:16501717

Secreted HSP Vaccine for Malaria Prophylaxis

DTIC Science & Technology

2017-10-01

thereby stimulating an avid, antigen specific, cytotoxic CD8 T cell response. Here we developed malaria vaccine that relies on secreted gp96-Ig...vaccine is expected to provide prophylactic immunity for malaria by removing infected liver cells before sporozoites can replicate and spread to the...vaccine to the immunogenicity of NMRC-M3V-D/Ad-PfCA vaccine. We found that gp96-Ig vaccination provided stronger antigen specific CD8 T cell

A DNA vaccine against yellow fever virus: development and evaluation.

PubMed

Maciel, Milton; Cruz, Fábia da Silva Pereira; Cordeiro, Marli Tenório; da Motta, Márcia Archer; Cassemiro, Klécia Marília Soares de Melo; Maia, Rita de Cássia Carvalho; de Figueiredo, Regina Célia Bressan Queiroz; Galler, Ricardo; Freire, Marcos da Silva; August, Joseph Thomas; Marques, Ernesto T A; Dhalia, Rafael

2015-04-01

Attenuated yellow fever (YF) virus 17D/17DD vaccines are the only available protection from YF infection, which remains a significant source of morbidity and mortality in the tropical areas of the world. The attenuated YF virus vaccine, which is used worldwide, generates both long-lasting neutralizing antibodies and strong T-cell responses. However, on rare occasions, this vaccine has toxic side effects that can be fatal. This study presents the design of two non-viral DNA-based antigen formulations and the characterization of their expression and immunological properties. The two antigen formulations consist of DNA encoding the full-length envelope protein (p/YFE) or the full-length envelope protein fused to the lysosomal-associated membrane protein signal, LAMP-1 (pL/YFE), aimed at diverting antigen processing/presentation through the major histocompatibility complex II precursor compartments. The immune responses triggered by these formulations were evaluated in H2b and H2d backgrounds, corresponding to the C57Bl/6 and BALB/c mice strains, respectively. Both DNA constructs were able to induce very strong T-cell responses of similar magnitude against almost all epitopes that are also generated by the YF 17DD vaccine. The pL/YFE formulation performed best overall. In addition to the T-cell response, it was also able to stimulate high titers of anti-YF neutralizing antibodies comparable to the levels elicited by the 17DD vaccine. More importantly, the pL/YFE vaccine conferred 100% protection against the YF virus in intracerebrally challenged mice. These results indicate that pL/YFE DNA is an excellent vaccine candidate and should be considered for further developmental studies.

A DNA Vaccine against Yellow Fever Virus: Development and Evaluation

PubMed Central

Maciel, Milton; Cruz, Fábia da Silva Pereira; Cordeiro, Marli Tenório; da Motta, Márcia Archer; Cassemiro, Klécia Marília Soares de Melo; Maia, Rita de Cássia Carvalho; de Figueiredo, Regina Célia Bressan Queiroz; Galler, Ricardo; Freire, Marcos da Silva; August, Joseph Thomas; Marques, Ernesto T. A.; Dhalia, Rafael

2015-01-01

Attenuated yellow fever (YF) virus 17D/17DD vaccines are the only available protection from YF infection, which remains a significant source of morbidity and mortality in the tropical areas of the world. The attenuated YF virus vaccine, which is used worldwide, generates both long-lasting neutralizing antibodies and strong T-cell responses. However, on rare occasions, this vaccine has toxic side effects that can be fatal. This study presents the design of two non-viral DNA-based antigen formulations and the characterization of their expression and immunological properties. The two antigen formulations consist of DNA encoding the full-length envelope protein (p/YFE) or the full-length envelope protein fused to the lysosomal-associated membrane protein signal, LAMP-1 (pL/YFE), aimed at diverting antigen processing/presentation through the major histocompatibility complex II precursor compartments. The immune responses triggered by these formulations were evaluated in H2b and H2d backgrounds, corresponding to the C57Bl/6 and BALB/c mice strains, respectively. Both DNA constructs were able to induce very strong T-cell responses of similar magnitude against almost all epitopes that are also generated by the YF 17DD vaccine. The pL/YFE formulation performed best overall. In addition to the T-cell response, it was also able to stimulate high titers of anti-YF neutralizing antibodies comparable to the levels elicited by the 17DD vaccine. More importantly, the pL/YFE vaccine conferred 100% protection against the YF virus in intracerebrally challenged mice. These results indicate that pL/YFE DNA is an excellent vaccine candidate and should be considered for further developmental studies. PMID:25875109

Bacteriophage T4 as a Nanoparticle Platform to Display and Deliver Pathogen Antigens: Construction of an Effective Anthrax Vaccine.

PubMed

Tao, Pan; Li, Qin; Shivachandra, Sathish B; Rao, Venigalla B

2017-01-01

Protein-based subunit vaccines represent a safer alternative to the whole pathogen in vaccine development. However, limitations of physiological instability and low immunogenicity of such vaccines demand an efficient delivery system to stimulate robust immune responses. The bacteriophage T4 capsid-based antigen delivery system can robustly elicit both humoral and cellular immune responses without any adjuvant. Therefore, it offers a strong promise as a novel antigen delivery system. Currently Bacillus anthracis, the causative agent of anthrax, is a serious biothreat agent and no FDA-approved anthrax vaccine is available for mass vaccination. Here, we describe a potential anthrax vaccine using a T4 capsid platform to display and deliver the 83 kDa protective antigen, PA, a key component of the anthrax toxin. This T4 vaccine platform might serve as a universal antigen delivery system that can be adapted to develop vaccines against any infectious disease.

Stabilized single-injection inactivated polio vaccine elicits a strong neutralizing immune response.

PubMed

Tzeng, Stephany Y; McHugh, Kevin J; Behrens, Adam M; Rose, Sviatlana; Sugarman, James L; Ferber, Shiran; Langer, Robert; Jaklenec, Ana

2018-05-21

Vaccination in the developing world is hampered by limited patient access, which prevents individuals from receiving the multiple injections necessary for protective immunity. Here, we developed an injectable microparticle formulation of the inactivated polio vaccine (IPV) that releases multiple pulses of stable antigen over time. To accomplish this, we established an IPV stabilization strategy using cationic polymers for pH modulation to enhance traditional small-molecule-based stabilization methods. We investigated the mechanism of this strategy and showed that it was broadly applicable to all three antigens in IPV. Our lead formulations released two bursts of IPV 1 month apart, mimicking a typical vaccination schedule in the developing world. One injection of the controlled-release formulations elicited a similar or better neutralizing response in rats, considered the correlate of protection in humans, than multiple injections of liquid vaccine. This single-administration vaccine strategy has the potential to improve vaccine coverage in the developing world. Copyright © 2018 the Author(s). Published by PNAS.

Stabilized single-injection inactivated polio vaccine elicits a strong neutralizing immune response

PubMed Central

Tzeng, Stephany Y.; McHugh, Kevin J.; Behrens, Adam M.; Rose, Sviatlana; Sugarman, James L.; Ferber, Shiran; Jaklenec, Ana

2018-01-01

Vaccination in the developing world is hampered by limited patient access, which prevents individuals from receiving the multiple injections necessary for protective immunity. Here, we developed an injectable microparticle formulation of the inactivated polio vaccine (IPV) that releases multiple pulses of stable antigen over time. To accomplish this, we established an IPV stabilization strategy using cationic polymers for pH modulation to enhance traditional small-molecule–based stabilization methods. We investigated the mechanism of this strategy and showed that it was broadly applicable to all three antigens in IPV. Our lead formulations released two bursts of IPV 1 month apart, mimicking a typical vaccination schedule in the developing world. One injection of the controlled-release formulations elicited a similar or better neutralizing response in rats, considered the correlate of protection in humans, than multiple injections of liquid vaccine. This single-administration vaccine strategy has the potential to improve vaccine coverage in the developing world. PMID:29784798

Designer vaccine nanodiscs for personalized cancer immunotherapy

NASA Astrophysics Data System (ADS)

Kuai, Rui; Ochyl, Lukasz J.; Bahjat, Keith S.; Schwendeman, Anna; Moon, James J.

2017-04-01

Despite the tremendous potential of peptide-based cancer vaccines, their efficacy has been limited in humans. Recent innovations in tumour exome sequencing have signalled the new era of personalized immunotherapy with patient-specific neoantigens, but a general methodology for stimulating strong CD8α+ cytotoxic T-lymphocyte (CTL) responses remains lacking. Here we demonstrate that high-density lipoprotein-mimicking nanodiscs coupled with antigen (Ag) peptides and adjuvants can markedly improve Ag/adjuvant co-delivery to lymphoid organs and sustain Ag presentation on dendritic cells. Strikingly, nanodiscs elicited up to 47-fold greater frequencies of neoantigen-specific CTLs than soluble vaccines and even 31-fold greater than perhaps the strongest adjuvant in clinical trials (that is, CpG in Montanide). Moreover, multi-epitope vaccination generated broad-spectrum T-cell responses that potently inhibited tumour growth. Nanodiscs eliminated established MC-38 and B16F10 tumours when combined with anti-PD-1 and anti-CTLA-4 therapy. These findings represent a new powerful approach for cancer immunotherapy and suggest a general strategy for personalized nanomedicine.

Biotechnology approaches to produce potent, self-adjuvanting antigen-adjuvant fusion protein subunit vaccines.

PubMed

Moyle, Peter Michael

Traditional vaccination approaches (e.g. live attenuated or killed microorganisms) are among the most effective means to prevent the spread of infectious diseases. These approaches, nevertheless, have failed to yield successful vaccines against many important pathogens. To overcome this problem, methods have been developed to identify microbial components, against which protective immune responses can be elicited. Subunit antigens identified by these approaches enable the production of defined vaccines, with improved safety profiles. However, they are generally poorly immunogenic, necessitating their administration with potent immunostimulatory adjuvants. Since few safe and effective adjuvants are currently used in vaccines approved for human use, with those available displaying poor potency, or an inability to stimulate the types of immune responses required for vaccines against specific diseases (e.g. cytotoxic lymphocytes (CTLs) to treat cancers), the development of new vaccines will be aided by the availability of characterized platforms of new adjuvants, improving our capacity to rationally select adjuvants for different applications. One such approach, involves the addition of microbial components (pathogen-associated molecular patterns; PAMPs), that can stimulate strong immune responses, into subunit vaccine formulations. The conjugation of PAMPs to subunit antigens provides a means to greatly increase vaccine potency, by targeting immunostimulation and antigen to the same antigen presenting cell. Thus, methods that enable the efficient, and inexpensive production of antigen-adjuvant fusions represent an exciting mean to improve immunity towards subunit antigens. Herein we review four protein-based adjuvants (flagellin, bacterial lipoproteins, the extra domain A of fibronectin (EDA), and heat shock proteins (Hsps)), which can be genetically fused to antigens to enable recombinant production of antigen-adjuvant fusion proteins, with a focus on their

Immune responses to mumps vaccine in adults who were vaccinated in childhood.

PubMed

Hanna-Wakim, Rima; Yasukawa, Linda L; Sung, Phillip; Arvin, Ann M; Gans, Hayley A

2008-06-15

In a mumps outbreak in the United States, many infected individuals were adults who had received 2 doses of mumps vaccine. The persistence of cellular immunity to mumps vaccine has not been defined. This was an observational, nonrandomized cohort study evaluating cell-mediated and humoral immunity to mumps in 10 vaccinated and 10 naturally immune adults. Mumps-specific T cell activation and interferon (IFN)-gamma production were measured using lymphoproliferative and flow cytometry assays, and mumps immunoglobulin (Ig) G was measured using enzyme-linked immunosorbent assay. T cell immunity to mumps was high in both groups; 70% of vaccinated and 80% of naturally immune individuals had a positive (> or =3) stimulation index (SI) (P = 1.0). The mean percentages of mumps-specific CD4+ T cells that expressed CD69 and produced IFN-gamma were equivalent in the 2 groups: 0.06% and 0.12%, respectively (P = .11). The mean SIs in the groups were also equivalent, although IFN-gamma concentrations from cultures stimulated with mumps antigen were higher in naturally immune adults than in vaccinated adults (P < or = .01). All adults were positive for mumps IgG. T and B cell immunity to mumps was detected in adults at least 10 years after immunization. Except for IFN-gamma release, responses in vaccinated adults paralleled those observed in naturally immune individuals.

Immune Responses to Mumps Vaccine in Adults Who Were Vaccinated in Childhood

PubMed Central

Hanna-Wakim, Rima; Yasukawa, Linda L.; Sung, Phillip; Arvin, Ann M.; Gans, Hayley A.

2008-01-01

Background In a mumps outbreak in the United States, many infected individuals were adults who had received 2 doses of mumps vaccine. The persistence of cellular immunity to mumps vaccine has not been defined. Methods This was an observational, nonrandomized cohort study evaluating cell-mediated and humoral immunity to mumps in 10 vaccinated and 10 naturally immune adults. Mumps-specific T cell activation and interferon (IFN)–γ production were measured using lymphoproliferative and flow cytometry assays, and mumps immunoglobulin (Ig) G was measured using enzyme-linked immunosorbent assay. Results T cell immunity to mumps was high in both groups; 70% of vaccinated and 80% of naturally immune individuals had a positive (≥3) stimulation index (SI) (P = 1.0). The mean percentages of mumps-specific CD4+ T cells that expressed CD69 and produced IFN-γ were equivalent in the 2 groups: 0.06% and 0.12%, respectively (P = .11). The mean SIs in the groups were also equivalent, although IFN-γ concentrations from cultures stimulated with mumps antigen were higher in naturally immune adults than in vaccinated adults (P ≤ .01). All adults were positive for mumps IgG. Conclusion T and B cell immunity to mumps was detected in adults at least 10 years after immunization. Except for IFN-γ release, responses in vaccinated adults paralleled those observed in naturally immune individuals. PMID:18419345

Immune Responses in Pigs Vaccinated with Adjuvanted and Non-Adjuvanted A(H1N1)pdm/09 Influenza Vaccines Used in Human Immunization Programmes

PubMed Central

Lefevre, Eric A.; Carr, B. Veronica; Inman, Charlotte F.; Prentice, Helen; Brown, Ian H.; Brookes, Sharon M.; Garcon, Fanny; Hill, Michelle L.; Iqbal, Munir; Elderfield, Ruth A.; Barclay, Wendy S.; Gubbins, Simon; Bailey, Mick; Charleston, Bryan

2012-01-01

Following the emergence and global spread of a novel H1N1 influenza virus in 2009, two A(H1N1)pdm/09 influenza vaccines produced from the A/California/07/09 H1N1 strain were selected and used for the national immunisation programme in the United Kingdom: an adjuvanted split virion vaccine and a non-adjuvanted whole virion vaccine. In this study, we assessed the immune responses generated in inbred large white pigs (Babraham line) following vaccination with these vaccines and after challenge with A(H1N1)pdm/09 virus three months post-vaccination. Both vaccines elicited strong antibody responses, which included high levels of influenza-specific IgG1 and haemagglutination inhibition titres to H1 virus. Immunisation with the adjuvanted split vaccine induced significantly higher interferon gamma production, increased frequency of interferon gamma-producing cells and proliferation of CD4−CD8+ (cytotoxic) and CD4+CD8+ (helper) T cells, after in vitro re-stimulation. Despite significant differences in the magnitude and breadth of immune responses in the two vaccinated and mock treated groups, similar quantities of viral RNA were detected from the nasal cavity in all pigs after live virus challenge. The present study provides support for the use of the pig as a valid experimental model for influenza infections in humans, including the assessment of protective efficacy of therapeutic interventions. PMID:22427834

Single laser pulse compression via strongly coupled stimulated Brillouin scattering in plasma

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

Peng, H.; Wu, Z. H.; Zhang, Z. M.

2016-07-15

Laser amplification in plasma, including stimulated Raman scattering amplification and strongly coupled stimulated Brillouin scattering (sc-SBS) amplification, is very promising to generate ultrahigh-power and ultrashort laser pulses. But both are quite complex in experiments: at least three different laser pulses must be prepared; temporal delay and spatial overlap of these three pulses are difficult. We propose a single pulse compression scheme based on sc-SBS in plasma. Only one moderately long laser is applied, the front part of which ionizes the gas to produced plasma, and gets reflected by a plasma mirror at the end of the gas channel. The reflectedmore » front quickly depletes the remaining part of the laser by sc-SBS in the self-similar regime. The output laser is much stronger and shorter. This scheme is at first considered theoretically, then validated by using 1D PIC simulations.« less

I strong administrative buy-in, firm mandates can push flu vaccination rates up to more than 99% among health care workers.

PubMed

2014-11-01

While flu vaccination rates are inching up among health care workers, there is still room for improvement. The Centers for Disease Control and Prevention reports that slightly more than 75% of health care workers received the flu vaccination during the 2013-14 season--an increase of roughly 3% over the 2012-13 season. However, some hospitals have been able to achieve vaccination rates in excess of 99%. The apparent key to these efforts is a firm mandate that all personnel receive a flu shot as a condition of employment. There is always pushback to such policies, but hospitals report that most personnel eventually come around. While flu vaccination rates are on the increase among health, care personnel, data from the Centers for Medicare and Medicaid Services (CMS) note that rates vary widely from state to state. For example, the vaccination rate for health care workers in New Jersey stood at just 62% last year. In contrast, more than 95% of health care workers in Maryland received the shot during the 2013-14 flu season. Both Loyola University Medical Center and Henry Ford Hospital have been able to boost flu vaccination rates among their health care workers to more than 99% with the implementation of policies that require flu shots as a condition of employment. Experts say successful flu vaccination campaigns require strong administration buy-in and physician leadership.

Duration of serum antibody responses following vaccination and revaccination of cattle with non-living commercial Pasteurella haemolytica vaccines.

PubMed

Confer, A W; Fulton, R W; Clinkenbeard, K D; Driskel, B A

1998-12-01

This study was designed to determine the duration of serum antibody responses to Pasteurella haemolytica whole cells (WC) and leukotoxin (LKT) in weanling beef cattle vaccinated with various non-living P. haemolytica vaccines. Serum antibodies to P. haemolytica antigens were determined periodically through day 140 by enzyme-linked immunosorbent assays. At day 140, cattle were revaccinated, and antibody responses periodically determined through day 196. Three vaccines were used in two experiments (A and B), OneShot, Presponse HP/tK, and Septimune PH-K. In general, all three vaccines between 7 and 14 days induced antibody responses to WC after vaccination. Antibodies to LKT were induced with OneShot and Presponse. Revaccination at days 28 and 140 usually stimulated anamnestic responses. Serum antibodies to the various antigens remained significantly increased for up to 84 days after vaccination or revaccination. The intensity and duration of antibody responses were variable depending on the experiment and vaccines used. Vaccination with OneShot usually stimulated the greatest responses to WC. Vaccination with OneShot or Presponse resulted in equivalent primary anti-LKT responses. In experiment B, spontaneous seroconversion was found in numerous calves on day 112. Revaccination of those cattle at day 140 resulted in markedly variable antibody responses such that several groups had no increase in antibody responses.

Benefits of gene transduction of granulocyte macrophage colony-stimulating factor in cancer vaccine using genetically modified dendritic cells.

PubMed

Ojima, Toshiyasu; Iwahashi, Makoto; Nakamura, Masaki; Matsuda, Kenji; Nakamori, Mikihito; Ueda, Kentaro; Naka, Teiji; Katsuda, Masahiro; Miyazawa, Motoki; Yamaue, Hiroki

2007-10-01

Granulocyte macrophage colony-stimulating factor (GM-CSF) is a key cytokine for the generation and stimulation of dendritic cells (DCs), and it may also play a pivotal role in promoting the survival of DCs. In this study, the feasibility of creating a cancer vaccine using DCs adenovirally transduced with the carcinoembryonic antigen (CEA) gene and the GM-CSF gene was examined. In addition, the effect of the co-transduction of GM-CSF gene on the lifespan of these genetically modified DCs was determined. A cytotoxic assay using peripheral blood mononuclear cell (PBMC)-derived cytotoxic T lymphocytes (CTLs) was performed in a 4-h 51Cr release assay. The apoptosis of DCs was examined by TdT-mediated dUTP-FITC nick end labeling (TUNEL) assay. CEA-specific CTLs were generated from PBMCs stimulated with genetically modified DCs expressing CEA. The cytotoxicity of these CTLs was augmented by co-transduction of DCs with the GM-CSF gene. Co-transduction of the GM-CSF gene into DCs inhibited apoptosis of these DCs themselves via up-regulation of Bcl-x(L) expression, leading to the extension of the lifespan of these DCs. Furthermore, the transduction of the GM-CSF gene into DCs also suppressed the incidence of apoptosis of DCs induced by transforming growth factor-beta1 (TGFbeta-1). Immunotherapy using these genetically modified DCs may therefore be useful with several advantages as follows: i) adenoviral toxicity to DCs can be reduced; ii) the lifespan of vaccinated DCs can be prolonged; and iii) GM-CSF may protect DCs from apoptosis induced by tumor-derived TGFbeta-1 in the regional lymph nodes.

Mucosal Vaccination with Heterologous Viral Vectored Vaccine Targeting Subdominant SIV Accessory Antigens Strongly Inhibits Early Viral Replication.

PubMed

Xu, Huanbin; Andersson, Anne-Marie; Ragonnaud, Emeline; Boilesen, Ditte; Tolver, Anders; Jensen, Benjamin Anderschou Holbech; Blanchard, James L; Nicosia, Alfredo; Folgori, Antonella; Colloca, Stefano; Cortese, Riccardo; Thomsen, Allan Randrup; Christensen, Jan Pravsgaard; Veazey, Ronald S; Holst, Peter Johannes

2017-04-01

Conventional HIV T cell vaccine strategies have not been successful in containing acute peak viremia, nor in providing long-term control. We immunized rhesus macaques intramuscularly and rectally using a heterologous adenovirus vectored SIV vaccine regimen encoding normally weakly immunogenic tat, vif, rev and vpr antigens fused to the MHC class II associated invariant chain. Immunizations induced broad T cell responses in all vaccinees. Following up to 10 repeated low-dose intrarectal challenges, vaccinees suppressed early viral replication (P=0.01) and prevented the peak viremia in 5/6 animals. Despite consistently undetectable viremia in 2 out of 6 vaccinees, all animals showed evidence of infection induced immune responses indicating that infection had taken place. Vaccinees, with and without detectable viremia better preserved their rectal CD4+ T cell population and had reduced immune hyperactivation as measured by naïve T cell depletion, Ki-67 and PD-1 expression on T cells. These results indicate that vaccination towards SIV accessory antigens vaccine can provide a level of acute control of SIV replication with a suggestion of beneficial immunological consequences in infected animals of unknown long-term significance. In conclusion, our studies demonstrate that a vaccine encoding subdominant antigens not normally associated with virus control can exert a significant impact on acute peak viremia. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Vaccination of cattle with Mycobacterium bovis BCG by a combination of systemic and oral routes.

PubMed

Buddle, Bryce M; Denis, Michel; Aldwell, Frank E; Martin Vordermeier, H; Glyn Hewinson, R; Neil Wedlock, D

2008-11-01

Mycobacterium bovis bacille Calmette-Guérin (BCG) vaccine delivered to calves by the subcutaneous (s.c.) or by the oral route in a formulated lipid matrix has been previously shown to induce similar levels of protection against bovine tuberculosis. The current study was aimed at determining whether a combination of delivering BCG by s.c. and oral routes would enhance levels of protection, compared to only one route of vaccination. Forty calves were randomly divided into four groups (10/group). Calves were vaccinated with 10(6)colony forming units (CFU) of BCG Pasteur by the s.c. route or orally with 10(9)CFU BCG incorporated into a lipid formulation. One group received a combination of BCG administered by both the s.c. and oral routes and a non-vaccinated group served as a control. The two groups of calves that received s.c. BCG produced strong IFN-gamma responses in whole blood cultures stimulated with bovine purified protein derivative (PPD) 3 weeks after vaccination. Cattle vaccinated just with oral BCG in a lipid matrix produced a strong IFN-gamma response 8 weeks after vaccination, and peaking at 11 weeks after vaccination. All calves were challenged by the intratracheal route with M. bovis 15 weeks after vaccination and were euthanized and necropsied to assess protection at 17 weeks following challenge. BCG given s.c. or orally induced significant and comparable levels of protection against the virulent challenge. Vaccination of cattle by a combination of s.c./oral routes did not enhance protection beyond that achieved by s.c. or oral vaccination alone. We conclude that vaccination of cattle with BCG by a combination of routes has no beneficial additive effects, compared to a single s.c. administration of BCG or BCG given orally in a lipid formulation.

Secreted HSP Vaccine for Malaria Prophylaxis

DTIC Science & Technology

2014-10-01

AWARD NUMBER: W81XWH-13-2-0098 TITLE: Secreted HSP Vaccine for Malaria Prophylaxis PRINCIPAL INVESTIGATOR: Dr. Eckhard R. Podack...model. 15. SUBJECT TERMS Malaria , Plasmodium Falciparum, circumsporozoite protein, apical membrane antigen-1, vaccine , heat shock proteins, gp96...approach to stimulate cytotoxic T cells against malaria antigens and investigate the optimal vaccination route to target these T cells to the liver. To

Humoral response to influenza vaccination in relation to pre-vaccination antibody titres, vaccination history, cytomegalovirus serostatus and CD4/CD8 ratio.

PubMed

Strindhall, Jan; Ernerudh, Jan; Mörner, Andreas; Waalen, Kristian; Löfgren, Sture; Matussek, Andreas; Bengner, Malin

2016-01-01

Annual vaccination against influenza virus is generally recommended to elderly and chronically ill, but the relative importance of factors influencing the outcome is not fully understood. In this study of 88 individuals all aged 69 years, the increase in haemagglutinin-inhibiting (HI) antibodies to trivalent inactivated influenza vaccine was correlated with HI titres before vaccination, prior vaccinations against influenza, cytomegalovirus serostatus and, as an estimate of immune risk profile, the ratio between CD4 + and CD8 + T cells. Vaccine responses were impaired by high pre-existing HI antibody titres. For influenza B repeated vaccinations and an inverse CD4/CD8 ratio had a negative impact on the vaccine response. Cytomegalovirus seropositivity had no apparent effect on HI titres before or after vaccination. It is concluded that both pre-existing HI antibodies and previous vaccinations to influenza may influence the humoral response to influenza vaccination and that a CD4/CD8 ratio < 1 may indicate an impaired ability to respond to repeated antigenic stimulation.

Co-expression of HIV-1 virus-like particles and granulocyte-macrophage colony stimulating factor by GEO-D03 DNA vaccine.

PubMed

Hellerstein, Michael; Xu, Yongxian; Marino, Tracie; Lu, Shan; Yi, Hong; Wright, Elizabeth R; Robinson, Harriet L

2012-11-01

Here, we report on GEO-D03, a DNA vaccine that co-expresses non-infectious HIV-1 virus-like particles (VLPs) and the human cytokine, granulocyte-macrophage colony-stimulating factor (GM-CSF). The virus-like particles display the native gp160 form of the HIV-1 Envelope glycoprotein (Env) and are designed to elicit antibody against the natural form of Env on virus and virus-infected cells. The DNA-expressed HIV Gag, Pol and Env proteins also have the potential to elicit virus-specific CD4 and CD8 T cells. The purpose of the co-expressed GM-CSF is to target a cytokine that recruits, expands and differentiates macrophages and dendritic cells to the site of VLP expression. The GEO-D03 DNA vaccine is currently entered into human trials as a prime for a recombinant modified vaccinia Ankara (MVA) boost. In preclinical studies in macaques using an SIV prototype vaccine, this vaccination regimen elicited both anti-viral T cells and antibody, and provided 70% protection against acquisition during 12 weekly rectal exposures with a heterologous SIV. Higher avidity of the Env-specific Ab for the native form of the Env in the challenge virus correlated with lower likelihood of SIV infection.

Self-Assembly DNA Polyplex Vaccine inside Dissolving Microneedles for High-Potency Intradermal Vaccination.

PubMed

Liao, Jing-Fong; Lee, Jin-Ching; Lin, Chun-Kuang; Wei, Kuo-Chen; Chen, Pin-Yuan; Yang, Hung-Wei

2017-01-01

The strong immunogenicity induction is the powerful weapon to prevent the virus infections. This study demonstrated that one-step synthesis of DNA polyplex vaccine in microneedle (MN) patches can induce high immunogenicity through intradermal vaccination and increase the vaccine stability for storage outside the cold chain. More negative charged DNA vaccine was entrapped into the needle region of MNs followed by DNA polyplex formation with branched polyethylenimine (bPEI) pre-coated in the cavities of polydimethylsiloxane (PDMS) molds that can deliver more DNA vaccine to immune-cell rich epidermis with high transfection efficiency. Our data in this study support the safety and immunogenicity of the MN-based vaccine; the MN patch delivery system induced an immune response 3.5-fold as strong as seen with conventional intramuscular administration; the DNA polyplex formulation provided excellent vaccine stability at high temperature (could be stored at 45ºC for at least 4 months); the DNA vaccine is expected to be manufactured at low cost and not generate sharps waste. We think this study is significant to public health because there is a pressing need for an effective vaccination in developing countries.

Induction of IL21 in Peripheral T Follicular Helper Cells Is an Indicator of Influenza Vaccine Response in a Previously Vaccinated HIV-Infected Pediatric Cohort.

PubMed

de Armas, Lesley R; Cotugno, Nicola; Pallikkuth, Suresh; Pan, Li; Rinaldi, Stefano; Sanchez, M Celeste; Gonzalez, Louis; Cagigi, Alberto; Rossi, Paolo; Palma, Paolo; Pahwa, Savita

2017-03-01

HIV-infected patients of all ages frequently underperform in response to seasonal influenza vaccination, despite virologic control of HIV. The molecular mechanisms governing this impairment, as well as predictive biomarkers for responsiveness, remain unknown. This study was performed in samples obtained prevaccination (T0) from HIV-infected children who received the 2012-2013 seasonal influenza vaccine. Response status was determined based on established criterion for hemagglutination inhibition titer; participants with a hemagglutination titer ≥1:40 plus a ≥4-fold increase over T0 at 3 wk postvaccination were designated as responders. All children had a history of prior influenza vaccinations. At T0, the frequencies of CD4 T cell subsets, including peripheral T follicular helper (pTfh) cells, which provide help to B cells for developing into Ab-secreting cells, were similar between responders and nonresponders. However, in response to in vitro stimulation with influenza A/California/7/2009 (H1N1) Ag, differential gene expression related to pTfh cell function was observed by Fluidigm high-density RT-PCR between responders and nonresponders. In responders, H1N1 stimulation at T0 also resulted in CXCR5 induction (mRNA and protein) in CD4 T cells and IL21 gene induction in pTfh cells that were strongly associated with H1N1-specific B cell responses postvaccination. In contrast, CD4 T cells of nonresponders exhibited increased expression of IL2 and STAT5 genes, which are known to antagonize peripheral Tfh cell function. These results suggest that the quality of pTfh cells at the time of immunization is important for influenza vaccine responses and provide a rationale for targeted, ex vivo Ag-driven molecular profiling of purified immune cells to detect predictive biomarkers of the vaccine response. Copyright © 2017 by The American Association of Immunologists, Inc.

Vaccines and Kawasaki disease.

PubMed

Esposito, Susanna; Bianchini, Sonia; Dellepiane, Rosa Maria; Principi, Nicola

2016-01-01

The distinctive immune system characteristics of children with Kawasaki disease (KD) could suggest that they respond in a particular way to all antigenic stimulations, including those due to vaccines. Moreover, treatment of KD is mainly based on immunomodulatory therapy. These factors suggest that vaccines and KD may interact in several ways. These interactions could be of clinical relevance because KD is a disease of younger children who receive most of the vaccines recommended for infectious disease prevention. This paper shows that available evidence does not support an association between KD development and vaccine administration. Moreover, it highlights that administration of routine vaccines is mandatory even in children with KD and all efforts must be made to ensure the highest degree of protection against vaccine-preventable diseases for these patients. However, studies are needed to clarify currently unsolved issues, especially issues related to immunologic interference induced by intravenous immunoglobulin and biological drugs.

Dissection of Antibody Specificities Induced by Yellow Fever Vaccination

PubMed Central

Vratskikh, Oksana; Stiasny, Karin; Zlatkovic, Jürgen; Tsouchnikas, Georgios; Jarmer, Johanna; Karrer, Urs; Roggendorf, Michael; Roggendorf, Hedwig; Allwinn, Regina; Heinz, Franz X.

2013-01-01

The live attenuated yellow fever (YF) vaccine has an excellent record of efficacy and one dose provides long-lasting immunity, which in many cases may last a lifetime. Vaccination stimulates strong innate and adaptive immune responses, and neutralizing antibodies are considered to be the major effectors that correlate with protection from disease. Similar to other flaviviruses, such antibodies are primarily induced by the viral envelope protein E, which consists of three distinct domains (DI, II, and III) and is presented at the surface of mature flavivirions in an icosahedral arrangement. In general, the dominance and individual variation of antibodies to different domains of viral surface proteins and their impact on neutralizing activity are aspects of humoral immunity that are not well understood. To gain insight into these phenomena, we established a platform of immunoassays using recombinant proteins and protein domains that allowed us to dissect and quantify fine specificities of the polyclonal antibody response after YF vaccination in a panel of 51 vaccinees as well as determine their contribution to virus neutralization by serum depletion analyses. Our data revealed a high degree of individual variation in antibody specificities present in post-vaccination sera and differences in the contribution of different antibody subsets to virus neutralization. Irrespective of individual variation, a substantial proportion of neutralizing activity appeared to be due to antibodies directed to complex quaternary epitopes displayed on the virion surface only but not on monomeric E. On the other hand, DIII-specific antibodies (presumed to have the highest neutralizing activity) as well as broadly flavivirus cross-reactive antibodies were absent or present at very low titers. These data provide new information on the fine specificity as well as variability of antibody responses after YF vaccination that are consistent with a strong influence of individual-specific factors

Dissection of antibody specificities induced by yellow fever vaccination.

PubMed

Vratskikh, Oksana; Stiasny, Karin; Zlatkovic, Jürgen; Tsouchnikas, Georgios; Jarmer, Johanna; Karrer, Urs; Roggendorf, Michael; Roggendorf, Hedwig; Allwinn, Regina; Heinz, Franz X

2013-01-01

The live attenuated yellow fever (YF) vaccine has an excellent record of efficacy and one dose provides long-lasting immunity, which in many cases may last a lifetime. Vaccination stimulates strong innate and adaptive immune responses, and neutralizing antibodies are considered to be the major effectors that correlate with protection from disease. Similar to other flaviviruses, such antibodies are primarily induced by the viral envelope protein E, which consists of three distinct domains (DI, II, and III) and is presented at the surface of mature flavivirions in an icosahedral arrangement. In general, the dominance and individual variation of antibodies to different domains of viral surface proteins and their impact on neutralizing activity are aspects of humoral immunity that are not well understood. To gain insight into these phenomena, we established a platform of immunoassays using recombinant proteins and protein domains that allowed us to dissect and quantify fine specificities of the polyclonal antibody response after YF vaccination in a panel of 51 vaccinees as well as determine their contribution to virus neutralization by serum depletion analyses. Our data revealed a high degree of individual variation in antibody specificities present in post-vaccination sera and differences in the contribution of different antibody subsets to virus neutralization. Irrespective of individual variation, a substantial proportion of neutralizing activity appeared to be due to antibodies directed to complex quaternary epitopes displayed on the virion surface only but not on monomeric E. On the other hand, DIII-specific antibodies (presumed to have the highest neutralizing activity) as well as broadly flavivirus cross-reactive antibodies were absent or present at very low titers. These data provide new information on the fine specificity as well as variability of antibody responses after YF vaccination that are consistent with a strong influence of individual-specific factors

Elicitation of strong immune responses by a DNA vaccine expressing a secreted form of hepatitis C virus envelope protein E2 in murine and porcine animal models

PubMed Central

Li, Yi-Ping; Kang, Hye Na; Babiuk, Lorne A; Liu, Qiang

2006-01-01

AIM: To characterize the immunogenicity of a hepatitis C virus (HCV) E2 DNA vaccine alone or with a protein vaccine boost in murine and porcine animal models. METHODS: A DNA vaccine expressing a secreted form of HCV E2 protein was constructed and used to vaccinate mice and piglets with or without boosting with a recombinant E2 protein vaccine formulated with CpG ODN and 10% Emulsigen. The immunogenicity of HCV E2 vaccines was analyzed by ELISA for antibody responses, MTT assay for lymphocyte proliferation, ELISPOT for the number of interferon-γ secreting cells, and cytotoxic T lymphocyte assays. RESULTS: Intradermal injection of E2 DNA vaccine induced strong Th1-like immune responses in mice. In piglets, E2 DNA vaccine elicited moderate and more balanced immune responses. A DNA vaccine prime and protein boost vaccination strategy induced significantly higher E2-specific antibody levels and shifted the immune response towards Th2-like ones in piglets. CONCLUSION: A DNA vaccine expressing a secreted form of HCV E2 protein elicited E2-specific immune responses in mice and piglets. Recombinant E2 protein vaccination following DNA immunization significantly increased the antibody response in piglets. These HCV E2 vaccines may represent promising hepatitis C vaccine candidates for further investigations. PMID:17131474

[Immune response to live influenza vaccine].

PubMed

Naĭkhin, A N; Rekstin, A R; Barantseva, I B; Donina, S A; Desheva, Iu A; Grigor'eva, E P; Kiseleva, I V; Rudenko, L G

2002-01-01

Priority data on the induction, by using a Russian live cold-adapted reassortant influenza vaccine (LIV), of the cellular and humoral immunity with regard for attenuation and genetic reassortment of vaccine stains as well as with regard for the age of vaccinated persons and the production of Th1 (IFNY, IL-2) and Th2 (IL-4) cytokine markers in vitro are presented. It was demonstrated in vivo that a pathogenic virus of the A group by far more actively induced the lymphocyte apoptosis as compared with attenuated genetically reassorted stains. Unlike the influenza pathogenic virus, the genetically attenuated and reassorted strain did not produce any negative effects on the induction of cellular immunity. A comparative study of the LIV immunogenic properties in vaccinated persons showed an advantage of LIV over inactivated influenza vaccine (IIV) in stimulating the cellular and local immunity in the elderly. Unlike IIV, LIV induced an active and balanced immune response developing due to Th1 and Th2 activation. LIV was found to stimulate well enough the production of IFN and IL-2 in both young and old persons.

[Pneumococcal vaccine: protection of adults and reduction of antibiotic resistence by vaccination of children with a conjugated vaccine].

PubMed

Pletz, Mathias W

2011-06-01

Pneumococcal infections (pneumonia, otitis media, sinusitis, meningitis) are common and usually involve toddlers, immunocompromised and the elderly. Main reservoir of pneumococci is the nasopharyngeal zone of healthy carriers, especially of toddlers. Currently, two types of pneumococcal vaccines are in clinical use, which induce production of antibodies against capsular polysaccharides. The older vaccine consists of pure capsular polysaccharides. It induces a limited immunity, because polysaccharides are poor antigens that stimulate mainly B-cells. In children under two years of age this vaccine is not used, because it does not induce a sufficient immunologic response, presumably because of the immaturity of their immune system. In 2000, a vaccination program with a novel pneumococcal vaccine was launched in the USA. This vaccine contains capsular polysaccharides, that are conjugated with a highly immunogenic protein. It induces both a T cell and B cell response that results in specific humoral and mucosal immunity. U.S. data demonstrate, that serotypes covered by the conjugated vaccine can be reduced in the whole population by vaccination of children being the main reservoir of pneumococci. This so called ,,herd protection" results in a decrease in invasive pneumococcal diseases in vaccinees and non-vaccinees as well as in a reduction of antibiotic resistance rates by reducing resistant pneumococcal cones.

Specific Dioscorea Phytoextracts Enhance Potency of TCL-Loaded DC-Based Cancer Vaccines

PubMed Central

Chang, Wei-Ting; Chen, Hui-Ming; Yin, Shu-Yi; Chen, Yung-Hsiang; Wen, Chih-Chun; Wei, Wen-Chi; Lai, Phoency; Wang, Cheng-Hsin; Yang, Ning-Sun

2013-01-01

Dioscorea tuber phytoextracts can confer immunomodulatory activities ex vivo and improve regeneration of bone marrow cells in vivo. In present study, we evaluated specific Dioscorea phytoextracts for use ex vivo as a bone-marrow-derived dendritic cell- (DC-) based vaccine adjuvant for cancer immunotherapy. Fractionated Dioscorea extracts (DsII) were assayed for their effect on maturation and functions of DC ex vivo and antimelanoma activity of DC-based vaccine in vivo. The phytoextract from 50–75% ethanol-precipitated fraction of Dioscorea alata var. purpurea Tainung no. 5 tuber, designated as DsII-TN5, showed a strong augmentation of tumor cell lysate- (TCL-) loaded DC-mediated activation of T-cell proliferation. DsII-TN5 stimulated the expression of CD40, CD80, CD86, and IL-1β in TCL-loaded DCs and downregulated the expression of TGF-β1. DC vaccines prepared by a specific schema (TCL (2 h) + LPS (22 h)) showed the strongest antitumor activity. DsII-TN5 as a DC vaccine adjuvant showed strong antimelanoma activity and reduced myeloid-derived suppressor cell (MDSC) population in tested mice. DsII-TN5 can also activate DCs to enhance Th1- and Th17-related cytokine expressions. Biochemical analysis showed that DsII-TN5 consists mainly of polysaccharides containing a high level (53%) of mannose residues. We suggest that DsII-TN5 may have potential for future application as a potent, cost-effective adjuvant for DC-based cancer vaccines. PMID:23935688

A review of oral vaccination with transgenic vegetables.

PubMed

Tacket, C O; Mason, H S

1999-08-01

Mucosal immunization of the gastrointestinal tract is an effective way to stimulate local and systemic immune responses. Oral vaccines must be formulated in such a way that antigens are protected as they pass through the adverse environment of the stomach and are delivered to the mucosal inductive sites. Vaccine antigens cloned into edible transgenic plants are a promising new delivery system for oral vaccines. Such vaccines could be safe, inexpensive, and multicomponent.

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.

N-(2-hydroxy) propyl-3-trimethylammonium chitosan chloride: An immune-enhancing adjuvant for hepatitis E virus recombinant polypeptide vaccine in mice.

PubMed

Tao, Wei; Zheng, Hai-Qun; Fu, Ting; He, Zhuo-Jing; Hong, Yan

2017-08-03

Adjuvants are essential for enhancing vaccine potency by improving the humoral and/or cell-mediated immune response to vaccine antigens. This study was performed to evaluate the immuno-enhancing characteristic of N-(2-hydroxy) propyl-3-trimethylammonium chitosan chloride (HTCC), the cationically modified chitosan, as an adjuvant for hepatitis E virus (HEV) recombinant polypeptide vaccine. Animal experiments showed that HTCC provides adjuvant activity when co-administered with HEV recombinant polypeptide vaccine by intramuscularly route. Vaccination using HTCC as an adjuvant was associated with increases of the serum HEV-specific IgG antibodies, splenocytes proliferation and the growths of CD4 + CD8 - T lymphocytes and IFN-γ-secreting T lymphocytes in peripheral blood. These findings suggested that HTCC had strong immuno-enhancing effect. Our findings are the first to demonstrate that HTCC is safe and effective in inducing a good antibody response and stimulating Th1-biased immune responses for HEV recombinant polypeptide vaccine.

Newcastle disease virus vectored vaccines as bivalent or antigen delivery vaccines

PubMed Central

2017-01-01

Recent advances in reverse genetics techniques make it possible to manipulate the genome of RNA viruses such as Newcastle disease virus (NDV). Several NDV vaccine strains have been used as vaccine vectors in poultry, mammals, and humans to express antigens of different pathogens. The safety, immunogenicity, and protective efficacy of these NDV-vectored vaccines have been evaluated in pre-clinical and clinical studies. The vaccines are safe in mammals, humans, and poultry. Bivalent NDV-vectored vaccines against pathogens of economic importance to the poultry industry have been developed. These bivalent vaccines confer solid protective immunity against NDV and other foreign antigens. In most cases, NDV-vectored vaccines induce strong local and systemic immune responses against the target foreign antigen. This review summarizes the development of NDV-vectored vaccines and their potential use as a base for designing other effective vaccines for veterinary and human use. PMID:28775971

Vaccination of school children with live mumps virus vaccine.

PubMed

Furesz, J; Nagler, F P

1970-05-30

Live, attenuated mumps virus vaccine (Mumpsvax) was administered to 146 school children 6 to 9 years of age. One child developed clinical mumps nine days after vaccination; epidemiological and serological data strongly suggest that this child had become infected before vaccination. Apart from this single instance there were no apparent clinical reactions that could be ascribed to the administration of the vaccine. Sixty-three of the 146 children with no clinical history of mumps had an initial serum neutralizing antibody titre of less than 1:2. Specific antibodies to mumps virus were detected in 93.5% of the sera of the susceptible children 28 days after vaccination, and the geometric mean antibody titre of these sera was low (1:6). Of the 80 initially seropositive children 21 (26.2%) showed a significant antibody response to the vaccine and this was influenced by the pre-existing antibody level. These data have further demonstrated the safety and efficacy of the live mumps vaccine in children.

Vaccination of School Children With Live Mumps Virus Vaccine

PubMed Central

Furesz, J.; Nagler, F. P.

1970-01-01

Live, attenuated mumps virus vaccine (Mumpsvax) was administered to 146 school children 6 to 9 years of age. One child developed clinical mumps nine days after vaccination; epidemiological and serological data strongly suggest that this child had become infected before vaccination. Apart from this single instance there were no apparent clinical reactions that could be ascribed to the administration of the vaccine. Sixty-three of the 146 children with no clinical history of mumps had an initial serum neutralizing antibody titre of less than 1:2. Specific antibodies to mumps virus were detected in 93.5% of the sera of the susceptible children 28 days after vaccination, and the geometric mean antibody titre of these sera was low (1:6). Of the 80 initially seropositive children 21 (26.2%) showed a significant antibody response to the vaccine and this was influenced by the pre-existing antibody level. These data have further demonstrated the safety and efficacy of the live mumps vaccine in children. PMID:5420994

Use of a LiESP/QA-21 Vaccine (CaniLeish) Stimulates an Appropriate Th1-Dominated Cell-Mediated Immune Response in Dogs

PubMed Central

Moreno, Javier; Vouldoukis, Ioannis; Martin, Virginie; McGahie, David; Cuisinier, Anne-Marie; Gueguen, Sylvie

2012-01-01

Canine leishmaniasis is an important zoonotic disease of dogs. The clinical outcome of infection is variable, with the efficiency of the immune response being the key determining factor. There is now a general consensus that a predominant Th1 immune profile in an overall mixed Th1/Th2 response is associated with resistance in dogs, and the absence of a strong Th1 influence is associated with a progression to clinical disease. As a result, there has been a growing demand for vaccines that can induce a specific, strong Th1 response. In this study, we measured the impact of a primary course of a newly available LiESP/QA-21 vaccine on selected humoral and cellular markers of the canine immune response during the onset of immunity. All vaccinated dogs developed a humoral response characterised by IgG2 production. More importantly, vaccinated dogs developed significantly stronger cell-mediated immunity responses than did control dogs. Vaccination induced specific cellular reactivity to soluble Leishmania antigens, with a Leishmania-specific lymphoproliferation (p = 0.0072), characterised by an increased population of T lymphocytes producing IFN-γ (p = 0.0021) and a significant ability of macrophages to reduce intracellular parasite burdens in vitro after co-culture with autologous lymphocytes (p = 0.0014). These responses were correlated with induction of the NOS pathway and production of NO derivatives, which has been shown to be an important leishmanicidal mechanism. These results confirm that vaccination with LiESP/QA-21 induces an appropriate Th1-profile cell-mediated response within three weeks of completing the primary course, and that this response effectively reduces the parasite load in pre-infected macrophages in vitro. PMID:22724031

Antibody and Cytokine Responses of Koalas (Phascolarctos cinereus) Vaccinated with Recombinant Chlamydial Major Outer Membrane Protein (MOMP) with Two Different Adjuvants

PubMed Central

Khan, Shahneaz Ali; Desclozeaux, Marion; Waugh, Courtney; Hanger, Jon; Loader, Jo; Gerdts, Volker; Potter, Andrew; Polkinghorne, Adam; Beagley, Kenneth; Timms, Peter

2016-01-01

Developing a vaccine against Chlamydia is key to combating widespread mortalities and morbidities associated with this infection in koalas (Phascolarctos cinereus). In previous studies, we have shown that two or three doses of a Recombinant Major Outer Membrane Protein (rMOMP) antigen-based vaccine, combined with immune stimulating complex (ISC) adjuvant, results in strong cellular and humoral immune responses in koalas. We have also separately evaluated a single dose vaccine, utilising a tri-adjuvant formula that comprises polyphosphazine based poly I: C and host defense peptides, with the same antigen. This formulation also produced strong cellular and humoral immune responses in captive koalas. In this current study, we directly compared the host immune responses of two sub-groups of wild Chlamydia negative koalas in one population vaccinated with the rMOMP protein antigen and adjuvanted with either the ISC or tri-adjuvant formula. Overall, both adjuvants produced strong Chlamydia-specific cellular (IFN-γ and IL-17A) responses in circulating PBMCs as well as MOMP-specific and functional, in vitro neutralising antibodies. While the immune responses were similar, there were adjuvant-specific immune differences between the two adjuvants, particularly in relation to the specificity of the MOMP epitope antibody responses. PMID:27219467

Co-administration of plasmid-encoded granulocyte-macrophage colony-stimulating factor increases human immunodeficiency virus-1 DNA vaccine-induced polyfunctional CD4+ T-cell responses

PubMed Central

Santana, Vinicius Canato; Almeida, Rafael Ribeiro; Ribeiro, Susan Pereira; Ferreira, Luís Carlos de Souza; Kalil, Jorge; Rosa, Daniela Santoro; Cunha-Neto, Edecio

2015-01-01

T-cell based vaccines against human immunodeficiency virus (HIV) generate specific responses that may limit both transmission and disease progression by controlling viral load. Broad, polyfunctional, and cytotoxic CD4+T-cell responses have been associated with control of simian immunodeficiency virus/HIV-1 replication, supporting the inclusion of CD4+ T-cell epitopes in vaccine formulations. Plasmid-encoded granulocyte-macrophage colony-stimulating factor (pGM-CSF) co-administration has been shown to induce potent CD4+ T-cell responses and to promote accelerated priming and increased migration of antigen-specific CD4+ T-cells. However, no study has shown whether co-immunisation with pGM-CSF enhances the number of vaccine-induced polyfunctional CD4+ T-cells. Our group has previously developed a DNA vaccine encoding conserved, multiple human leukocyte antigen (HLA)-DR binding HIV-1 subtype B peptides, which elicited broad, polyfunctional and long-lived CD4+ T-cell responses. Here, we show that pGM-CSF co-immunisation improved both magnitude and quality of vaccine-induced T-cell responses, particularly by increasing proliferating CD4+ T-cells that produce simultaneously interferon-γ, tumour necrosis factor-α and interleukin-2. Thus, we believe that the use of pGM-CSF may be helpful for vaccine strategies focused on the activation of anti-HIV CD4+ T-cell immunity. PMID:26602876

Safety Analysis of Leishmania Vaccine Used in a Randomized Canine Vaccine/Immunotherapy Trial.

PubMed

Toepp, Angela; Larson, Mandy; Grinnage-Pulley, Tara; Bennett, Carolyne; Anderson, Michael; Parrish, Molly; Fowler, Hailie; Wilson, Geneva; Gibson-Corely, Katherine; Gharpure, Radhika; Cotter, Caitlin; Petersen, Christine

2018-05-01

In Leishmania infantum -endemic countries, controlling infection within dogs, the domestic reservoir, is critical to public health. There is a need for safe vaccines that prevent canine progression with disease and transmission to others. Protective vaccination against Leishmania requires mounting a strong, inflammatory, Type 1 response. Three commercially available canine vaccines on the global veterinary market use saponin or inflammatory antigen components (Letifend) as a strong pro-inflammatory adjuvant. There is very little information detailing safety of saponin as an adjuvant in field trials. Safety analyses for the use of vaccine as an immunotherapeutic in asymptomatically infected animals are completely lacking. Leishmania infantum , the causative agent of canine leishmaniasis, is enzootic within U.S. hunting hounds. We assessed the safety of LeishTec ® after use in dogs from two different clinical states: 1) without clinical signs and tested negative on polymerase chain reaction and serology or 2) without clinical signs and positive for at least one Leishmania diagnostic test. Vaccine safety was assessed after all three vaccinations to quantify the number and severity of adverse events. Vaccinated animals had an adverse event rate of 3.09%, whereas placebo animals had 0.68%. Receiving vaccine was correlated with the occurrence of mild, site-specific, reactions. Occurrence of severe adverse events was not associated with having received vaccine. Infected, asymptomatic animals did not have a higher rate of adverse events. Use of vaccination is, therefore, likely to be safe in infected, asymptomatic animals.

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

Granulocyte-Macrophage Colony-Stimulating Factor Priming plus Papillomavirus E6 DNA Vaccination: Effects on Papilloma Formation and Regression in the Cottontail Rabbit Papillomavirus-Rabbit Model

PubMed Central

Leachman, Sancy A.; Tigelaar, Robert E.; Shlyankevich, Mark; Slade, Martin D.; Irwin, Michele; Chang, Ed; Wu, T. C.; Xiao, Wei; Pazhani, Sundaram; Zelterman, Daniel; Brandsma, Janet L.

2000-01-01

A cottontail rabbit papillomavirus (CRPV) E6 DNA vaccine that induces significant protection against CRPV challenge was used in a superior vaccination regimen in which the cutaneous sites of vaccination were primed with an expression vector encoding granulocyte-macrophage colony-stimulating factor (GM-CSF), a cytokine that induces differentiation and local recruitment of professional antigen-presenting cells. This treatment induced a massive influx of major histocompatibility complex class II-positive cells. In a vaccination-challenge experiment, rabbit groups were treated by E6 DNA vaccination, GM-CSF DNA inoculation, or a combination of both treatments. After two immunizations, rabbits were challenged with CRPV at low, moderate, and high stringencies and monitored for papilloma formation. As expected, all clinical outcomes were monotonically related to the stringency of the viral challenge. The results demonstrate that GM-CSF priming greatly augmented the effects of CRPV E6 vaccination. First, challenge sites in control rabbits (at the moderate challenge stringency) had a 0% probability of remaining disease free, versus a 50% probability in E6-vaccinated rabbits, and whereas GM-CSF alone had no effect, the interaction between GM-CSF priming and E6 vaccination increased disease-free survival to 67%. Second, the incubation period before papilloma onset was lengthened by E6 DNA vaccination alone or to some extent by GM-CSF DNA inoculation alone, and the combination of treatments induced additive effects. Third, the rate of papilloma growth was reduced by E6 vaccination and, to a lesser extent, by GM-CSF treatment. In addition, the interaction between the E6 and GM-CSF treatments was synergistic and yielded more than a 99% reduction in papilloma volume. Finally, regression occurred among the papillomas that formed in rabbits treated with the E6 vaccine and/or with GM-CSF, with the highest regression frequency occurring in rabbits that received the combination

Severe post-vaccination reaction to 17D yellow fever vaccine in Nigeria.

PubMed

Oyelami, S A; Olaleye, O D; Oyejide, C O; Omilabu, S A; Fatunla, B A

1994-01-01

An unusual outbreak of post-vaccination reactions to 17D yellow fever vaccine occurred at Shaki, Nigeria, in May 1987. Twenty-five of the affected people were treated at the Baptist Hospital Shaki. The patients presented with rapidly progressing swelling of the left arm with associated fever and other constitutional symptoms few hours after inoculation with the vaccine. Some of the patients developed gangrene of the affected limb, five of them went into coma and died. Poor hygiene and improper handling of vaccine as well as contamination of vaccine from the source are possible causes. A review of vaccine delivery strategies especially at local community levels; sound training, supervision of vaccinators and health education are strongly recommended to prevent reoccurrence of similar reactions.

Vaccinating high-risk children with the intranasal live-attenuated influenza vaccine: the Quebec experience.

PubMed

Quach, Caroline

2014-12-01

Given the burden of illness associated with influenza, vaccination is recommended for individuals at high risk of complications. The live-attenuated influenza vaccine (LAIV) is administered by intranasal spray, thus directly stimulating mucosal immunity. In this review, we aimed to provide evidence for its efficacy and safety in different paediatric populations. We also share the Quebec experience of LAIV use through a publicly funded vaccination program for children with chronic, high-risk conditions. from randomized controlled trials in healthy children and in asthmatics have demonstrated superior efficacy of LAIV over the injectable vaccine (IIV). LAIV is well tolerated: its administration is associated with runny nose and nasal congestion, but not with asthma exacerbations and is well tolerated in children with cystic fibrosis, when compared to IIV. The vaccine is well accepted by children and parents and can easily be part of vaccination clinics in paediatric tertiary care centres targeting children with chronic, high-risk conditions, not leading to immunosuppression. Copyright © 2014 Elsevier Ltd. All rights reserved.

Adverse Reactions to Vaccination: From Anaphylaxis to Autoimmunity.

PubMed

Gershwin, Laurel J

2018-03-01

Vaccines are important for providing protection from infectious diseases. Vaccination initiates a process that stimulates development of a robust and long-lived immune response to the disease agents in the vaccine. Side effects are sometimes associated with vaccination. These vary from development of acute hypersensitivity responses to vaccine components to local tissue reactions that are annoying but not significantly detrimental to the patient. The pathogenesis of these responses and the consequent clinical outcomes are discussed. Overstimulation of the immune response and the potential relationship to autoimmunity is evaluated in relation to genetic predisposition. Copyright © 2017 Elsevier Inc. All rights reserved.

Ki-67 expression reveals strong, transient influenza specific CD4 T cell responses after adult vaccination.

PubMed

Li, Xi; Miao, Hongyu; Henn, Alicia; Topham, David J; Wu, Hulin; Zand, Martin S; Mosmann, Tim R

2012-06-29

Although previous studies have found minimal changes in CD4 T cell responses after vaccination of adults with trivalent inactivated influenza vaccine, daily sampling and monitoring of the proliferation marker Ki-67 have now been used to reveal that a substantial fraction of influenza-specific CD4 T cells respond to vaccination. At 4-6 days after vaccination, there is a sharp rise in the numbers of Ki-67-expressing PBMC that produce IFNγ, IL-2 and/or TNFα in vitro in response to influenza vaccine or peptide. Ki-67(+) cell numbers then decline rapidly, and 10 days after vaccination, both Ki-67(+) and overall influenza-specific cell numbers are similar to pre-vaccination levels. These results provide a tool for assessing the quality and quantity of CD4 T cell responses to different influenza vaccines, and raise the possibility that the anti-influenza T cell memory response may be qualitatively altered by vaccination, even if the overall memory cell numbers do not change significantly. Copyright © 2012. Published by Elsevier Ltd.

Dairy cows produce cytokine and cytotoxic T cell responses following vaccination with an antigenic fraction from Streptococcus uberis.

PubMed

Wedlock, D Neil; Buddle, Bryce M; Williamson, John; Lacy-Hulbert, S Jane; Turner, Sally-Anne; Subharat, Supatsak; Heiser, Axel

2014-07-15

Streptococcus uberis is a major cause of mastitis in dairy cows worldwide and currently, there is no vaccine commercially available against this form of mastitis. In the current study, cell-free extracts (CFE) were prepared from each of three different S. uberis strains, designated as #3, #24 and #363 representative of the three main sequence types of S. uberis that cause mastitis in New Zealand. These proteins were formulated into vaccines with Emulsigen-D and the immunogenicity of the vaccines was determined in both calves and dairy cows. Two groups of calves (n=5/group) were vaccinated subcutaneously with CFE from strain #24 or strains #3, #24 and #363 formulated with Emulsigen-D, respectively. A third group (n=5) was vaccinated with CFE from the three strains formulated with Emulsigen-D and also containing recombinant bovine granulocyte macrophage colony-stimulating factor while, a control group (n=5) was not vaccinated. Vaccinated animals produced strong antibody responses to the S. uberis antigens and an antigen-specific cytotoxic effect against blood monocytes/macrophages that had phagocytosed S. uberis, with no significant differences in responses observed between the three vaccinated groups. In a second trial, the safety and immunogenicity of the vaccine containing CFE from all three strains of S. uberis and Emulsigen-D was determined in dairy cows. A group of six cows were vaccinated subcutaneously at 3 and 1 week prior to dry off and revaccinated 2-3 weeks before calving. Immune responses in blood and mammary gland secretions (MGS) were monitored during the dry period and in the subsequent lactation. The vaccine was well tolerated with no adverse effect from vaccination observed in any of the cows. Vaccination induced an antigen-specific cytotoxic effect against blood monocytes/macrophages that had phagocytosed S. uberis, moderate antigen-specific IFN-γ responses in blood and strong antibody responses in both blood and MGS. In conclusion, the results

Has Their Son Been Vaccinated? Beliefs About Other Parents Matter for Human Papillomavirus Vaccine.

PubMed

Schuler, Christine L; Coyne-Beasley, Tamera

2016-07-01

The goal of this study was to determine if parents' beliefs about social norms of human papillomavirus (HPV) vaccination for sons were associated with knowledge of HPV, intention to vaccinate sons, or beliefs about side effects. A cross-sectional, survey-based study of parents with sons was performed in 2010. Fisher's exact tests were used to examine associations between demographics and responses about social norms. Multivariate logistic regression models examined beliefs about social norms of male HPV vaccination and primary outcomes. Few parents agreed that others were vaccinating sons (n = 31/267, 12%), including 1% responding strongly agree and 11% responding agree. Most parents, 52%, disagreed that others were vaccinating (40% disagree, 11% strongly disagree), and 37% chose prefer not to answer regarding others' vaccination practices. Hispanic parents and those with a high school education or less were significantly more likely to choose prefer not to answer than their respective counterparts regarding vaccination norms. In multivariate models, parents agreeing others were vaccinating sons had greater odds of having high knowledge of HPV (adjusted odds ratio [aOR] high vs low knowledge 3.15, 95% confidence interval [CI] 1.13, 8.77) and increased intention to vaccinate sons (n = 243, aOR = 4.41, 95% CI = 1.51, 12.89). Beliefs about side effects were not significantly associated with beliefs about social norms. Parents' beliefs about others' vaccination practices are important with regard to knowledge of HPV and intention to vaccinate sons. Studying how various public messages about HPV vaccine may influence normative beliefs could be relevant to improving vaccination coverage. © The Author(s) 2015.

Strong coupling and stimulated emission in single parabolic quantum well microcavity for terahertz cascade

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

Tzimis, A.; Savvidis, P. G.; Institute of Electronic Structure and Laser, Foundation for Research and Technology - Hellas, 71110 Heraklion, Crete

2015-09-07

We report observation of strong light-matter coupling in an AlGaAs microcavity (MC) with an embedded single parabolic quantum well. The parabolic potential is achieved by varying aluminum concentration along the growth direction providing equally spaced energy levels, as confirmed by Brewster angle reflectivity from a reference sample without MC. It acts as an active region of the structure which potentially allows cascaded emission of terahertz (THz) light. Spectrally and time resolved pump-probe spectroscopy reveals characteristic quantum beats whose frequencies range from 0.9 to 4.5 THz, corresponding to energy separation between relevant excitonic levels. The structure exhibits strong stimulated nonlinear emissionmore » with simultaneous transition to weak coupling regime. The present study highlights the potential of such devices for creating cascaded relaxation of bosons, which could be utilized for THz emission.« less

Gelatin-induced T-cell activation in children with nonanaphylactic-type reactions to vaccines containing gelatin.

PubMed

Taniguchi, K; Fujisawa, T; Ihara, T; Kamiya, H

1998-12-01

Many cases of anaphylactic or nonanaphylactic reactions have been reported to measles-mumps-rubella vaccine or its component vaccines that contain gelatin as a stabilizer. Increased levels of specific IgE antibodies to gelatin have been reported in children with anaphylactic reactions. However, IgE is not increased in cases of nonanaphylactic reaction, and the mechanisms of the reaction are still controversial. The study was aimed to elucidate the relationship between nonanaphylactic reaction and gelatin. We investigated in vitro induction of activated memory helper T cells (CD4(+ )CD25(+ )CD45RO+ cells) in response to gelatin in children with nonanaphylactic reactions to vaccines containing gelatin. In patients with delayed-type sensitivity to gelatin confirmed with a positive skin test response, CD4(+ )CD25(+ )CD45RO+ cells were significantly more strongly induced in culture containing gelatin than in control cultures. However, there was no significant difference between cultures with gelatin and those with control solvent in patients without reactions after vaccination. Of 76 patients with nonanaphylactic reactions after immunization with vaccine containing gelatin, 61 had an increased lymphocyte stimulation index to gelatin versus control children. These results suggest the possibility that nonanaphylactic reactions to gelatin-containing vaccine in Japan might be mediated by delayed hypersensitivity reactions against gelatin.

Listeria Vaccines for Pancreatic Cancer

DTIC Science & Technology

2013-10-01

produced 52.8 mg of LLO protein, assessed purity using SDS- PAGE and examined endotoxin levels using a Limulus Amebocyte Lysate (LAL) gel clotting test...contrast, HKLM effectively stimulated BMDM to produce cytokines with similar magnitude as observed with LPS. The inability of LLO to activate BMDM was...explored the capacity of Listeria vaccines to induce anti-tumor T cell immunity in the KPC model. We have found that Listeria vaccines produce

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.

Neonatal Vaccination: Challenges and Intervention Strategies.

PubMed

Morris, Matthew C; Surendran, Naveen

2016-01-01

While vaccines have been tremendously successful in reducing the incidence of serious infectious diseases, newborns remain particularly vulnerable in the first few months of their life to life-threatening infections. A number of challenges exist to neonatal vaccination. However, recent advances in the understanding of neonatal immunology offer insights to overcome many of those challenges. This review will present an overview of the features of neonatal immunity which make vaccination difficult, survey the mechanisms of action of available vaccine adjuvants with respect to the unique features of neonatal immunity, and propose a possible mechanism contributing to the inability of neonates to generate protective immune responses to vaccines. We surveyed recent published findings on the challenges to neonatal vaccination and possible intervention strategies including the use of novel vaccine adjuvants to develop efficacious neonatal vaccines. Challenges in the vaccination of neonates include interference from maternal antibody and excessive skewing towards Th2 immunity, which can be counteracted by the use of proper adjuvants. Synergistic stimulation of multiple Toll-like receptors by incorporating well-defined agonist-adjuvant combinations to vaccines is a promising strategy to ensure a protective vaccine response in neonates. © 2016 S. Karger AG, Basel.

Modes of Action for Mucosal Vaccine Adjuvants.

PubMed

Aoshi, Taiki

Vaccine adjuvants induce innate immune responses and the addition of adjuvants to the vaccine helps to induce protective immunity in the host. Vaccines utilizing live attenuated or killed whole pathogens usually contain endogenous adjuvants, such as bacterial cell wall products and their genomic nucleic acids, which act as pathogen-associated molecular patterns and are sufficient to induce adaptive immune responses. However, purified protein- or antigen-based vaccines, including component or recombinant vaccines, usually lose these endogenous innate immune stimulators, so the addition of an exogenous adjuvant is essential for the success of these vaccine types. Although this adjuvant requirement is mostly the same for parental and mucosal vaccines, the development of mucosal vaccine adjuvants requires the specialized consideration of adapting the adjuvants to characteristic mucosal conditions. This review provides a brief overview of mucosa-associated immune response induction processes, such as antigen uptake and dendritic cell subset-dependent antigen presentation. It also highlights several mucosal vaccine adjuvants from recent reports, particularly focusing on their modes of action.

Activation of chicken bone marrow-derived dendritic cells induced by a Salmonella Enteritidis ghost vaccine candidate.

PubMed

Kamble, N M; Jawale, C V; Lee, J H

2016-10-01

Bacterial Ghost-based vaccine development has been applied to a variety of gram-negative bacteria. Developed Salmonella Enteritidis (S. Enteritidis) ghost are promising vaccine candidates because of their immunogenic and enhanced biosafety potential. In this study, we aimed to evaluate the immunostimulatory effect of a S. Enteritidis ghost vaccine on the maturation of chicken bone marrow-derived dendritic cells (chBM-DCs) in vitro The immature chBM-DCs were stimulated with S. Enteritidis ghost vaccine candidate. The vaccine efficiently stimulated maturation events in chBM-DCs, indicated by up-regulated expression of CD40, CD80, and MHC-II molecules. Immature BM-DCs responded to stimulation with S. Enteritidis ghost by increased expression of IL-6 and IL-12p40 cytokines. Also, S. Enteritidis ghost stimulated chBM-DCs induced the significant expression of IFN-γ and IL-2 in co-cultured autologous CD4+ T cells. In conclusion, our data suggest that S. Enteritidis ghost vaccine candidate is capable of activating and interacting with chBM-DCs. The results from current study may help for rational designing of Salmonella ghost based heterologous antigen delivery platforms to dendritic cells. © 2016 Poultry Science Association Inc.

A practical approach to pancreatic cancer immunotherapy using resected tumor lysate vaccines processed to express α-gal epitopes

PubMed Central

Miyoshi, Eiji; Eguchi, Hidetoshi; Nagano, Hiroaki; Matsunami, Katsuyoshi; Nagaoka, Satoshi; Yamada, Daisaku; Asaoka, Tadafumi; Noda, Takehiro; Wada, Hiroshi; Kawamoto, Koichi; Goto, Kunihito; Taniyama, Kiyomi; Mori, Masaki; Doki, Yuichiro

2017-01-01

Objectives Single-agent immunotherapy is ineffective against poorly immunogenic cancers, including pancreatic ductal adenocarcinoma (PDAC). The aims of this study were to demonstrate the feasibility of production of novel autologous tumor lysate vaccines from resected PDAC tumors, and verify vaccine safety and efficacy. Methods Fresh surgically resected tumors obtained from human patients were processed to enzymatically synthesize α-gal epitopes on the carbohydrate chains of membrane glycoproteins. Processed membranes were analyzed for the expression of α-gal epitopes and the binding of anti-Gal, and vaccine efficacy was assessed in vitro and in vivo. Results Effective synthesis of α-gal epitopes was demonstrated after processing of PDAC tumor lysates from 10 different patients, and tumor lysates readily bound an anti-Gal monoclonal antibody. α-gal(+) PDAC tumor lysate vaccines elicited strong antibody production against multiple tumor-associated antigens and activated multiple tumor-specific T cells. The lysate vaccines stimulated a robust immune response in animal models, resulting in tumor suppression and a significant improvement in survival without any adverse events. Conclusions Our data suggest that α-gal(+) PDAC tumor lysate vaccination may be a practical and effective new immunotherapeutic approach for treating pancreatic cancer. PMID:29077749

A practical approach to pancreatic cancer immunotherapy using resected tumor lysate vaccines processed to express α-gal epitopes.

PubMed

Furukawa, Kenta; Tanemura, Masahiro; Miyoshi, Eiji; Eguchi, Hidetoshi; Nagano, Hiroaki; Matsunami, Katsuyoshi; Nagaoka, Satoshi; Yamada, Daisaku; Asaoka, Tadafumi; Noda, Takehiro; Wada, Hiroshi; Kawamoto, Koichi; Goto, Kunihito; Taniyama, Kiyomi; Mori, Masaki; Doki, Yuichiro

2017-01-01

Single-agent immunotherapy is ineffective against poorly immunogenic cancers, including pancreatic ductal adenocarcinoma (PDAC). The aims of this study were to demonstrate the feasibility of production of novel autologous tumor lysate vaccines from resected PDAC tumors, and verify vaccine safety and efficacy. Fresh surgically resected tumors obtained from human patients were processed to enzymatically synthesize α-gal epitopes on the carbohydrate chains of membrane glycoproteins. Processed membranes were analyzed for the expression of α-gal epitopes and the binding of anti-Gal, and vaccine efficacy was assessed in vitro and in vivo. Effective synthesis of α-gal epitopes was demonstrated after processing of PDAC tumor lysates from 10 different patients, and tumor lysates readily bound an anti-Gal monoclonal antibody. α-gal(+) PDAC tumor lysate vaccines elicited strong antibody production against multiple tumor-associated antigens and activated multiple tumor-specific T cells. The lysate vaccines stimulated a robust immune response in animal models, resulting in tumor suppression and a significant improvement in survival without any adverse events. Our data suggest that α-gal(+) PDAC tumor lysate vaccination may be a practical and effective new immunotherapeutic approach for treating pancreatic cancer.

Tuberculosis vaccine development: strength lies in tenacity.

PubMed

Kaufmann, Stefan H E

2012-07-01

The past decade has witnessed a tremendous increase in the development of novel vaccines against tuberculosis (TB). In mice, each of these vaccine candidates stimulates an immune response that reduces the bacillary load, reflecting control but not sterilization of infection. Yet, the immune mechanisms underlying vaccine efficacy are only partially understood. In parallel to clinical assessment of current candidates, the next generation of vaccine candidates still needs to be developed. This requires basic research on how to induce the most efficacious immune response. Equally important is the dissection of immune responses in patients, latently infected healthy individuals, and participants of clinical vaccine trials. Amalgamation of this information will foster the way towards more efficacious vaccination strategies that not only prevent disease, but prevent or abolish infection. Copyright © 2012 Elsevier Ltd. All rights reserved.

Vaccine antigens modulate the innate response of monocytes to Al(OH)3

PubMed Central

Brummelman, Jolanda; van Els, Cécile A. C. M.; Marino, Fabio; Heck, Albert J. R.; van Riet, Elly; Metz, Bernard; Kersten, Gideon F. A.; Pennings, Jeroen L. A.; Meiring, Hugo D.

2018-01-01

Aluminum-based adjuvants have widely been used in human vaccines since 1926. In the absence of antigens, aluminum-based adjuvants can initiate the inflammatory preparedness of innate cells, yet the impact of antigens on this response has not been investigated so far. In this study, we address the modulating effect of vaccine antigens on the monocyte-derived innate response by comparing processes initiated by Al(OH)3 and by Infanrix, an Al(OH)3-adjuvanted trivalent combination vaccine (DTaP), containing diphtheria toxoid (D), tetanus toxoid (T) and acellular pertussis (aP) vaccine antigens. A systems-wide analysis of stimulated monocytes was performed in which full proteome analysis was combined with targeted transcriptome analysis and cytokine analysis. This comprehensive study revealed four major differences in the monocyte response, between plain Al(OH)3 and DTaP stimulation conditions: (I) DTaP increased the anti-inflammatory cytokine IL-10, whereas Al(OH)3 did not; (II) Al(OH)3 increased the gene expression of IFNγ, IL-2 and IL-17a in contrast to the limited induction or even downregulation by DTaP; (III) increased expression of type I interferons-induced proteins was not observed upon DTaP stimulation, but was observed upon Al(OH)3 stimulation; (IV) opposing regulation of protein localization pathways was observed for Al(OH)3 and DTaP stimulation, related to the induction of exocytosis by Al(OH)3 alone. This study highlights that vaccine antigens can antagonize Al(OH)3-induced programming of the innate immune responses at the monocyte level. PMID:29813132

Development of male contraceptive vaccine--a perspective.

PubMed

Moudgal, N R; Jeyakumar, M; Krishnamurthy, H N; Sridhar, S; Krishnamurthy, H; Martin, F

1997-01-01

This paper reviews the recent advances that have occurred in the area of development of a male contraceptive vaccine. The vaccine candidates considered for review are hormone/hormone receptor-based proteins including luteinizing hormone-releasing hormone (LHRH)/LH, follicle stimulating hormone (FSH), as well as LH and FSH receptor proteins. The review also highlights the advances in our basic understanding of gonadotrophin action which have led to development of these vaccines. Focus is mainly on studies in the non-human primate which may be directly relevant to projected studies in the human. The data indicate that the vaccines are well tolerated by the primate (including the human based on limited data) and do not give rise to any known toxic symptoms or immediate health hazards. The response to the immunogen has been uniform and it may be possible to increase antibody titres as well as prolong the immune response by adding acceptable immune stimulators to the adjuvant cocktail and developing better immunization schedules or immunogen delivery systems. Contraceptive vaccines for the male are a feasible proposition and attention should now be focussed on evaluating carefully the bioefficacy of antibodies raised to recombinant ovine FSHbeta or FSH receptor protein fragments in both human and non-human primates. The advantage of the FSH/FSH receptor over the LHRH/LH-based vaccine lies in the fact that the former does not require an exogenous testosterone supplement to maintain accessory gland function, libido etc. The LHRH/LH-based vaccine results in azoospermia, while the FSH vaccine causes the production of low numbers of poor quality spermatozoa which are incapable of impregnating cycling females.

Vaccine strategies: Optimising outcomes.

PubMed

Hardt, Karin; Bonanni, Paolo; King, Susan; Santos, Jose Ignacio; El-Hodhod, Mostafa; Zimet, Gregory D; Preiss, Scott

2016-12-20

Successful immunisation programmes generally result from high vaccine effectiveness and adequate uptake of vaccines. In the development of new vaccination strategies, the structure and strength of the local healthcare system is a key consideration. In high income countries, existing infrastructures are usually used, while in less developed countries, the capacity for introducing new vaccines may need to be strengthened, particularly for vaccines administered beyond early childhood, such as the measles or human papillomavirus (HPV) vaccine. Reliable immunisation service funding is another important factor and low income countries often need external supplementary sources of finance. Many regions also obtain support in generating an evidence base for vaccination via initiatives created by organisations including World Health Organization (WHO), the Pan American Health Organization (PAHO), the Agence de Médecine Préventive and the Sabin Vaccine Institute. Strong monitoring and surveillance mechanisms are also required. An example is the efficient and low-cost approaches for measuring the impact of the hepatitis B control initiative and evaluating achievement of goals that have been established in the WHO Western Pacific region. A review of implementation strategies reveals differing degrees of success. For example, in the Americas, PAHO advanced a measles-mumps-rubella vaccine strategy, targeting different population groups in mass, catch-up and follow-up vaccination campaigns. This has had much success but coverage data from some parts of the region suggest that children are still not receiving all appropriate vaccines, highlighting problems with local service infrastructures. Stark differences in coverage levels are also observed among high income countries, as is the case with HPV vaccine implementation in the USA versus the UK and Australia, reflecting differences in delivery settings. Experience and research have shown which vaccine strategies work well and the

Impact of committed individuals on vaccination behavior

NASA Astrophysics Data System (ADS)

Liu, Xiao-Tao; Wu, Zhi-Xi; Zhang, Lianzhong

2012-11-01

We study how the presence of committed vaccinators, a small fraction of individuals who consistently hold the vaccinating strategy and are immune to influence, impact the vaccination dynamics in well-mixed and spatially structured populations. For this purpose, we develop an epidemiological game-theoretic model of a flu-like vaccination by integrating an epidemiological process into a simple agent-based model of adaptive learning, where individuals (except for those committed ones) use anecdotal evidence to estimate costs and benefits of vaccination. We show that the committed vaccinators, acting as “steadfast role models” in the populations, can efficiently avoid the clustering of susceptible individuals and stimulate other imitators to take vaccination, hence contributing to the promotion of vaccine uptake. We substantiate our findings by making comparative studies of our model on a full lattice and on a randomly diluted one. Our work is expected to provide valuable information for decision-making and design more effective disease-control strategy.

Physician communication about adolescent vaccination: How is human papillomavirus vaccine different?

PubMed

Gilkey, Melissa B; Moss, Jennifer L; Coyne-Beasley, Tamera; Hall, Megan E; Shah, Parth D; Brewer, Noel T

2015-08-01

Low human papillomavirus (HPV) vaccination coverage stands in stark contrast to our success in delivering other adolescent vaccines. To identify opportunities for improving physicians' recommendations for HPV vaccination, we sought to understand how the communication context surrounding adolescent vaccination varies by vaccine type. A national sample of 776 U.S. physicians (53% pediatricians, 47% family medicine physicians) completed our online survey in 2014. We assessed physicians' perceptions and communication practices related to recommending adolescent vaccines for 11- and 12-year-old patients. About three-quarters of physicians (73%) reported recommending HPV vaccine as highly important for patients, ages 11-12. More physicians recommended tetanus, diphtheria, and acellular pertussis (Tdap) (95%) and meningococcal vaccines (87%, both p<0.001) as highly important for this age group. Only 13% of physicians perceived HPV vaccine as being highly important to parents, which was far fewer than perceived parental support for Tdap (74%) and meningococcal vaccines (62%, both p<0.001). Physicians reported that discussing HPV vaccine took almost twice as long as discussing Tdap. Among physicians with a preferred order for discussing adolescent vaccines, most (70%) discussed HPV vaccine last. Our findings suggest that primary care physicians perceived HPV vaccine discussions to be burdensome, requiring more time and engendering less parental support than other adolescent vaccines. Perhaps for this reason, physicians in our national study recommended HPV vaccine less strongly than other adolescent vaccines, and often chose to discuss it last. Communication strategies are needed to support physicians in recommending HPV vaccine with greater confidence and efficiency. Copyright © 2015 Elsevier Inc. All rights reserved.

Tumor cell-derived microparticles: a new form of cancer vaccine.

PubMed

Zhang, Huafeng; Huang, Bo

2015-08-01

For cancer vaccines, tumor antigen availability is currently not an issue due to technical advances. However, the generation of optimal immune stimulation during vaccination is challenging. We have recently demonstrated that tumor cell-derived microparticles (MP) can function as a new form of potent cancer vaccine by efficiently activating type I interferon pathway in a cGAS/STING dependent manner.

Emerging human papillomavirus vaccines

PubMed Central

Ma, Barbara; Maraj, Bharat; Tran, Nam Phuong; Knoff, Jayne; Chen, Alexander; Alvarez, Ronald D; Hung, Chien-Fu; Wu, T.-C.

2013-01-01

Introduction Identification of human papillomavirus (HPV) as the etiologic factor of cervical, anogenital, and a subset of head and neck cancers has stimulated the development of preventive and therapeutic HPV vaccines to control HPV-associated malignancies. Excitement has been generated by the commercialization of two preventive L1-based vaccines, which use HPV virus-like particles (VLPs) to generate capsid-specific neutralizing antibodies. However, factors such as high cost and requirement for cold chain have prevented widespread implementation where they are needed most. Areas covered Next generation preventive HPV vaccine candidates have focused on cost-effective stable alternatives and generating broader protection via targeting multivalent L1 VLPs, L2 capsid protein, and chimeric L1/L2 VLPs. Therapeutic HPV vaccine candidates have focused on enhancing T cell-mediated killing of HPV-transformed tumor cells, which constitutively express HPV-encoded proteins, E6 and E7. Several therapeutic HPV vaccines are in clinical trials. Expert opinion Although progress is being made, cost remains an issue inhibiting the use of preventive HPV vaccines in countries that carry the majority of the cervical cancer burden. In addition, progression of therapeutic HPV vaccines through clinical trials may require combination strategies employing different therapeutic modalities. As research in the development of HPV vaccines continues, we may generate effective strategies to control HPV-associated malignancies. PMID:23163511

Immunogenicity and protective efficacy of DMT liposome-adjuvanted tuberculosis subunit CTT3H vaccine

PubMed Central

Teng, Xindong; Tian, Maopeng; Li, Jianrong; Tan, Songwei; Yuan, Xuefeng; Yu, Qi; Jing, Yukai; Zhang, Zhiping; Yue, Tingting; Zhou, Lei; Fan, Xionglin

2015-01-01

Different strategies have been proposed for the development of protein subunit vaccine candidates for tuberculosis (TB), which shows better safety than other types of candidates and the currently used Bacillus Calmette-Guérin (BCG) vaccine. In order to develop more effective protein subunits depending on the mechanism of cell-mediated immunity against TB, a polyprotein CTT3H, based on 5 immunodominant antigens (CFP10, TB10.4, TB8.4, Rv3615c, and HBHA) with CD8+ epitopes of Mycobacterium tuberculosis, was constructed in this study. We vaccinated C57BL/6 mice with a TB subunit CTT3H protein in an adjuvant of dimethyldioctadecylammonium/monophosphoryl lipid A/trehalose 6,6′-dibehenate (DDA/MPL/TDB, DMT) liposome to investigate the immunogenicity and protective efficacy of this novel vaccine. Our results demonstrated that DMT liposome-adjuvanted CTT3H vaccine not only induced an antigen-specific CD4+ Th1 response, but also raised the number of PPD- and CTT3H-specific IFN-γ+ CD8+ T cells and elicited strong CTL responses against TB10.4, which provided more effective protection against a 60 CFU M. tuberculosis aerosol challenge than PBS control and DMT adjuvant alone. Our findings indicate that DMT-liposome is an effective adjuvant to stimulate CD8+ T cell responses and the DMT-adjuvanted subunit CTT3H vaccine is a promising candidate for the next generation of TB vaccine. PMID:25905680

Immunogenicity and protective efficacy of DMT liposome-adjuvanted tuberculosis subunit CTT3H vaccine.

PubMed

Teng, Xindong; Tian, Maopeng; Li, Jianrong; Tan, Songwei; Yuan, Xuefeng; Yu, Qi; Jing, Yukai; Zhang, Zhiping; Yue, Tingting; Zhou, Lei; Fan, Xionglin

2015-01-01

Different strategies have been proposed for the development of protein subunit vaccine candidates for tuberculosis (TB), which shows better safety than other types of candidates and the currently used Bacillus Calmette-Guérin (BCG) vaccine. In order to develop more effective protein subunits depending on the mechanism of cell-mediated immunity against TB, a polyprotein CTT3H, based on 5 immunodominant antigens (CFP10, TB10.4, TB8.4, Rv3615c, and HBHA) with CD8(+) epitopes of Mycobacterium tuberculosis, was constructed in this study. We vaccinated C57BL/6 mice with a TB subunit CTT3H protein in an adjuvant of dimethyldioctadecylammonium/monophosphoryl lipid A/trehalose 6,6'-dibehenate (DDA/MPL/TDB, DMT) liposome to investigate the immunogenicity and protective efficacy of this novel vaccine. Our results demonstrated that DMT liposome-adjuvanted CTT3H vaccine not only induced an antigen-specific CD4(+) Th1 response, but also raised the number of PPD- and CTT3H-specific IFN-γ(+) CD8(+) T cells and elicited strong CTL responses against TB10.4, which provided more effective protection against a 60 CFU M. tuberculosis aerosol challenge than PBS control and DMT adjuvant alone. Our findings indicate that DMT-liposome is an effective adjuvant to stimulate CD8(+) T cell responses and the DMT-adjuvanted subunit CTT3H vaccine is a promising candidate for the next generation of TB vaccine.

Novel Injectable Pentablock Copolymer Based Thermoresponsive Hydrogels for Sustained Release Vaccines.

PubMed

Bobbala, Sharan; Tamboli, Viral; McDowell, Arlene; Mitra, Ashim K; Hook, Sarah

2016-01-01

The need for multiple vaccinations to enhance the immunogenicity of subunit vaccines may be reduced by delivering the vaccine over an extended period of time. Here, we report two novel injectable pentablock copolymer based thermoresponsive hydrogels made of polyethyleneglycol-polycaprolactone-polylactide-polycaprolactone-polyethyleneglycol (PEG-PCL-PLA-PCL-PEG) with varying ratios of polycaprolactone (PCL) and polylactide (PLA), as single shot sustained release vaccines. Pentablock copolymer hydrogels were loaded with vaccine-encapsulated poly lactic-co-glycolic acid nanoparticles (PLGA-NP) or with the soluble vaccine components. Incorporation of PLGA-NP into the thermoresponsive hydrogels increased the complex viscosity of the gels, lowered the gelation temperature, and minimized the burst release of antigen and adjuvants. The two pentablock hydrogels stimulated both cellular and humoral responses. The addition of PLGA-NP to the hydrogels sustained immune responses for up to 49 days. The polymer with a higher ratio of PCL to PLA formed a more rigid gel, induced stronger immune responses, and stimulated effective anti-tumor responses in a prophylactic melanoma tumor model.

Altered Memory T-Cell Responses to Bacillus Calmette-Guerin and Tetanus Toxoid Vaccination and Altered Cytokine Responses to Polyclonal Stimulation in HIV-Exposed Uninfected Kenyan Infants.

PubMed

Garcia-Knight, Miguel A; Nduati, Eunice; Hassan, Amin S; Gambo, Faith; Odera, Dennis; Etyang, Timothy J; Hajj, Nassim J; Berkley, James Alexander; Urban, Britta C; Rowland-Jones, Sarah L

2015-01-01

Implementation of successful prevention of mother-to-child transmission of HIV strategies has resulted in an increased population of HIV-exposed uninfected (HEU) infants. HEU infants have higher rates of morbidity and mortality than HIV-unexposed (HU) infants. Numerous factors may contribute to poor health in HEU infants including immunological alterations. The present study assessed T-cell phenotype and function in HEU infants with a focus on memory Th1 responses to vaccination. We compared cross-sectionally selected parameters at 3 and 12 months of age in HIV-exposed (n = 42) and HU (n = 28) Kenyan infants. We measured ex vivo activated and bulk memory CD4 and CD8 T-cells and regulatory T-cells by flow cytometry. In addition, we measured the magnitude, quality and memory phenotype of antigen-specific T-cell responses to Bacillus Calmette-Guerin and Tetanus Toxoid vaccine antigens, and the magnitude and quality of the T cell response following polyclonal stimulation with staphylococcal enterotoxin B. Finally, the influence of maternal disease markers on the immunological parameters measured was assessed in HEU infants. Few perturbations were detected in ex vivo T-cell subsets, though amongst HEU infants maternal HIV viral load positively correlated with CD8 T cell immune activation at 12 months. Conversely, we observed age-dependent differences in the magnitude and polyfunctionality of IL-2 and TNF-α responses to vaccine antigens particularly in Th1 cells. These changes mirrored those seen following polyclonal stimulation, where at 3 months, cytokine responses were higher in HEU infants compared to HU infants, and at 12 months, HEU infant cytokine responses were consistently lower than those seen in HU infants. Finally, reduced effector memory Th1 responses to vaccine antigens were observed in HEU infants at 3 and 12 months and higher central memory Th1 responses to M. tuberculosis antigens were observed at 3 months only. Long-term monitoring of vaccine efficacy

A Systematic Review of Recent Advances in Equine Influenza Vaccination

PubMed Central

Paillot, Romain

2014-01-01

Equine influenza (EI) is a major respiratory disease of horses, which is still causing substantial outbreaks worldwide despite several decades of surveillance and prevention. Alongside quarantine procedures, vaccination is widely used to prevent or limit spread of the disease. The panel of EI vaccines commercially available is probably one of the most varied, including whole inactivated virus vaccines, Immuno-Stimulating Complex adjuvanted vaccines (ISCOM and ISCOM-Matrix), a live attenuated equine influenza virus (EIV) vaccine and a recombinant poxvirus-vectored vaccine. Several other strategies of vaccination are also evaluated. This systematic review reports the advances of EI vaccines during the last few years as well as some of the mechanisms behind the inefficient or sub-optimal response of horses to vaccination. PMID:26344892

Vaccines: Shaping global health.

PubMed

Pagliusi, Sonia; Ting, Ching-Chia; Lobos, Fernando

2017-03-14

The Developing Countries Vaccine Manufacturers' Network (DCVMN) gathered leaders in immunization programs, vaccine manufacturing, representatives of the Argentinean Health Authorities and Pan American Health Organization, among other global health stakeholders, for its 17th Annual General Meeting in Buenos Aires, to reflect on how vaccines are shaping global health. Polio eradication and elimination of measles and rubella from the Americas is a result of successful collaboration, made possible by timely supply of affordable vaccines. After decades of intense competition for high-value markets, collaboration with developing countries has become critical, and involvement of multiple manufacturers as well as public- and private-sector investments are essential, for developing new vaccines against emerging infectious diseases. The recent Zika virus outbreak and the accelerated Ebola vaccine development exemplify the need for international partnerships to combat infectious diseases. A new player, Coalition for Epidemic Preparedness Innovations (CEPI) has made its entrance in the global health community, aiming to stimulate research preparedness against emerging infections. Face-to-face panel discussions facilitated the dialogue around challenges, such as risks of viability to vaccine development and regulatory convergence, to improve access to sustainable vaccine supply. It was discussed that joint efforts to optimizing regulatory pathways in developing countries, reducing registration time by up to 50%, are required. Outbreaks of emerging infections and the global Polio eradication and containment challenges are reminders of the importance of vaccines' access, and of the importance of new public-private partnerships. Copyright © 2017.

Vaccine-derived polioviruses.

PubMed

Agol, Vadim I

2006-06-01

The Sabin oral poliovaccine (OPV) is extremely efficacious and safe, despite its inherent genetic instability. While reversion to nearly wild-type phenotype regularly occurs soon after the onset of OPV reproduction in the gastro-intestinal tract of vaccine recipients or their contacts, this is usually not a big problem, provided the vaccine is used either for mass vaccination or in populations with a relatively high level of anti-polio immunity. However, if these conditions are not met, the vaccine viruses are likely to be converted into highly transmissible agents with a nearly wild-type level of neurovirulence. Moreover, OPV viruses may persist and evolve even in adequately immunized populations. The current strategy for the "endgame" of poliovirus eradication envisions cessation of OPV usage shortly after the last isolation of a wild poliovirus. If implemented, this strategy would result in rapid growth of non-immune human populations at the time when OPV derivatives would very likely be persisting. Therefore, the planned cessation of OPV vaccination is associated with a very high, and in the author's opinion, unacceptable risk of polio outbreaks caused by OPV derivatives. The only currently available tool to curb such outbreaks is OPV, which should have been used at a global scale. Safe discontinuation of OPV vaccination will be possible only after an efficient new vaccine or an anti-poliovirus drug is available. To achieve this goal, stimulation of poliovirus research and elimination of organizational and financial obstacles preventing it are needed.

Neurologic complications of vaccinations.

PubMed

Miravalle, Augusto A; Schreiner, Teri

2014-01-01

This chapter reviews the most common neurologic disorders associated with common vaccines, evaluates the data linking the disorder with the vaccine, and discusses the potential mechanism of disease. A literature search was conducted in PubMed using a combination of the following terms: vaccines, vaccination, immunization, and neurologic complications. Data were also gathered from publications of the American Academy of Pediatrics Committee on Infectious Diseases, the World Health Organization, the US Centers for Disease Control and Prevention, and the Vaccine Adverse Event Reporting System. Neurologic complications of vaccination are rare. Many associations have been asserted without objective data to support a causal relationship. Rarely, patients with a neurologic complication will have a poor outcome. However, most patients recover fully from the neurologic complication. Vaccinations have altered the landscape of infectious disease. However, perception of risk associated with vaccinations has limited the success of disease eradication measures. Neurologic complications can be severe, and can provoke fear in potential vaccines. Evaluating whether there is causal link between neurologic disorders and vaccinations, not just temporal association, is critical to addressing public misperception of risk of vaccination. Among the vaccines available today, the cost-benefit analysis of vaccinations and complications strongly argues in favor of vaccination. © 2014 Elsevier B.V. All rights reserved.

Novel adjuvants & delivery vehicles for vaccines development: a road ahead.

PubMed

Mohan, Teena; Verma, Priyanka; Rao, D Nageswara

2013-11-01

The pure recombinant and synthetic antigens used in modern day vaccines are generally less immunogenic than older style live/attenuated and killed whole organism vaccines. One can improve the quality of vaccine production by incorporating immunomodulators or adjuvants with modified delivery vehicles viz. liposomes, immune stimulating complexes (ISCOMs), micro/nanospheres apart from alum, being used as gold standard. Adjuvants are used to augment the effect of a vaccine by stimulating the immune system to respond to the vaccine, more vigorously, and thus providing increased immunity to a particular disease. Adjuvants accomplish this task by mimicking specific sets of evolutionary conserved molecules which include lipopolysaccharides (LPS), components of bacterial cell wall, endocytosed nucleic acids such as dsRNA, ssDNA and unmethylated CpG dinucleotide containing DNA. This review provides information on various vaccine adjuvants and delivery vehicles being developed to date. From literature, it seems that the humoral immune responses have been observed for most adjuvants and delivery platforms while viral-vector, ISCOMs and Montanides have shown cytotoxic T-cell response in the clinical trials. MF59 and MPL® have elicited Th1 responses, and virus-like particles (VLPs), non-degradable nanoparticle and liposomes have also generated cellular immunity. Such vaccine components have also been evaluated for alternative routes of administration with clinical success reported for intranasal delivery of viral-vectors and proteosomes and oral delivery of VLP vaccines.

Novel adjuvants & delivery vehicles for vaccines development: A road ahead

PubMed Central

Mohan, Teena; Verma, Priyanka; Rao, D. Nageswara

2013-01-01

The pure recombinant and synthetic antigens used in modern day vaccines are generally less immunogenic than older style live/attenuated and killed whole organism vaccines. One can improve the quality of vaccine production by incorporating immunomodulators or adjuvants with modified delivery vehicles viz. liposomes, immune stimulating complexes (ISCOMs), micro/nanospheres apart from alum, being used as gold standard. Adjuvants are used to augment the effect of a vaccine by stimulating the immune system to respond to the vaccine, more vigorously, and thus providing increased immunity to a particular disease. Adjuvants accomplish this task by mimicking specific sets of evolutionary conserved molecules which include lipopolysaccharides (LPS), components of bacterial cell wall, endocytosed nucleic acids such as dsRNA, ssDNA and unmethylated CpG dinucleotide containing DNA. This review provides information on various vaccine adjuvants and delivery vehicles being developed to date. From literature, it seems that the humoral immune responses have been observed for most adjuvants and delivery platforms while viral-vector, ISCOMs and Montanides have shown cytotoxic T-cell response in the clinical trials. MF59 and MPL® have elicited Th1 responses, and virus-like particles (VLPs), non-degradable nanoparticle and liposomes have also generated cellular immunity. Such vaccine components have also been evaluated for alternative routes of administration with clinical success reported for intranasal delivery of viral-vectors and proteosomes and oral delivery of VLP vaccines. PMID:24434331

Modes of Action for Mucosal Vaccine Adjuvants

PubMed Central

2017-01-01

Abstract Vaccine adjuvants induce innate immune responses and the addition of adjuvants to the vaccine helps to induce protective immunity in the host. Vaccines utilizing live attenuated or killed whole pathogens usually contain endogenous adjuvants, such as bacterial cell wall products and their genomic nucleic acids, which act as pathogen-associated molecular patterns and are sufficient to induce adaptive immune responses. However, purified protein- or antigen-based vaccines, including component or recombinant vaccines, usually lose these endogenous innate immune stimulators, so the addition of an exogenous adjuvant is essential for the success of these vaccine types. Although this adjuvant requirement is mostly the same for parental and mucosal vaccines, the development of mucosal vaccine adjuvants requires the specialized consideration of adapting the adjuvants to characteristic mucosal conditions. This review provides a brief overview of mucosa-associated immune response induction processes, such as antigen uptake and dendritic cell subset-dependent antigen presentation. It also highlights several mucosal vaccine adjuvants from recent reports, particularly focusing on their modes of action. PMID:28436755

Immunogenicity of sanofi pasteur tetravalent dengue vaccine.

PubMed

Guy, Bruno

2009-10-01

A candidate tetravalent (TV) dengue vaccine based on the yellow fever (YF) 17D vaccine has been developed by sanofi pasteur. This dengue TV vaccine induced a controlled dendritic cell stimulation in vitro. In clinical trials, Th1 and CD8 responses were induced with an IFN-gamma/TNF-alpha ratio favouring IFN-gamma in both cases, regardless of whether the vaccine recipients were flavivirus naive or not. There was an absence of Th2 response in all cases. The Th1 response was dominated by the D4 serotype in flavivirus naive individuals after initial vaccination but broadened to include all serotypes after second vaccination. This broadened response was also observed after primary dengue TV vaccination in subjects previously administered monovalent live-attenuated dengue 1 and dengue 2 vaccines. Notably, virtually no cross-reactivity between YF 17D and dengue NS3 antigens at the CD8 level was observed. Clinical and pre-clinical results support the favourable immunogenicity and short-term safety of the dengue TV. Future studies will establish the longevity of the vaccine-induced immunity and requirements for boosters.

Towards a human oral vaccine for anthrax: the utility of a Salmonella Typhi Ty21a-based prime boost immunization strategy

PubMed Central

Baillie, Leslie W.J.; Rodriguez, Ana L.; Moore, Stephen; Atkins, Helen S.; Feng, Chiguang; Nataro, James P.; Pasetti, Marcela F.

2008-01-01

We previously demonstrated the ability of an orally administered attenuated Salmonella enterica serovar Typhimurium strain expressing the protective antigen (PA) of Bacillus anthracis to confer protection against lethal anthrax aerosol spore challenge [1]. To extend the utility of this approach to humans we constructed variants of S. enterica serovar Typhi Ty21a, an attenuated typhoid vaccine strain licensed for human use, which expressed and exported PA via two distinct plasmid-based transport systems: the Escherichia coli HlyA haemolysin and the S. Typhi ClyA export apparatus. Murine immunogenicity studies confirmed the ability of these constructs, especially Ty21a expressing the ClyA-PA fusion protein, to stimulate strong PA-specific immune responses following intranasal immunization. These responses were further enhanced by a subsequent boost with either parenterally delivered recombinant PA or the licensed US human alum-adsorbed anthrax vaccine (AVA). Anthrax toxin neutralizing antibody responses using this prime-boost regimen were rapid, vigorous and broad in nature. The results of this study demonstrate the feasibility of employing a mucosal prime with a licensed Salmonella Typhi vaccine strain followed by a parenteral protein boost to stimulate rapid protective immunity against anthrax. PMID:18805452

"To each his own": Discussions of vaccine decision-making in top parenting blogs.

PubMed

Meleo-Erwin, Zoë; Basch, Corey; MacLean, Sarah A; Scheibner, Courtney; Cadorett, Valerie

2017-08-03

Although social media provides a way for people to congregate with like-minded others, it can also play a role in spreading misinformation about public health interventions. Previous research demonstrates that parents who use the Internet to gather information on vaccination are more likely to hold anti-vaccination beliefs. There has been little examination of vaccination decision-making discussions on parenting blogs. This study seeks to fill that gap. Posts and comments on the top 25 top parenting blogs were analyzed using a mixed-method approach. Comments were analyzed using deductive coding scheme that examined whether content areas of interest were present or absent in vaccination discussions. Posts were coded inductively using a thematic analysis. Posts and comments were further coded as strongly vaccine-discouraging, vaccine-ambivalent, or strongly vaccine-encouraging. Finally, posts were grouped by year of publication and comments were analyzed within each group to examine the evolution of vaccination decision-making discussions in the parenting blogosphere over the past decade. Fifty-two percent of posts were categorized as strongly vaccine-discouraging and were most commonly associated with expressions of individual liberty. Comments were nearly 3 times as likely to strongly discourage vaccination than to strongly encourage it. Comments on the oldest posts (2006-2009), were more likely to strongly discourage vaccination (p = 0.008), whereas comments on newer posts (2013-2015), were more likely to strongly encourage vaccination (p = 0.003). These findings suggest there is a need for public health professionals to understand the concerns being expressed in these forums, and develop innovative ways to dispel anti-vaccination myths, as these views may create obstacles in the meeting the goals of the public health agenda.

InCVAX, a novel in situ autologous cancer vaccine (Conference Presentation)

NASA Astrophysics Data System (ADS)

Lam, Samuel Siu Kit; Chen, Wei R.

2017-02-01

Cancer immunotherapy is the concept of harnessing our own immune system to fight against cancer cells. The most attractive features of immunotherapy include relatively low toxicities compared to traditional therapies (surgery, chemotherapy and radiation), the possibility of eliminating distant metastases and the potential of preventing relapses. After decades of research, its therapeutic efficacy has finally been recognized and a number of approaches has been approved by the FDA over the past 10 years. Dendritic cell vaccine and checkpoint blockade strategies were among the first to enter the clinic, with many other strategies such as peptide vaccine, whole cell tumor vaccine, and adoptive T cell transfer (with Chimeric Antigen Receptors) etc. closely following in clinical trials. Immunophotonics is developing a novel in situ autologous cancer vaccine (InCVAX) by combining thermal laser phototherapy with immunotherapy. InCVAX is a two-step procedure: (1) Delivery of low-power thermal laser to any accessible tumor to cause partial cell death, increase tumor immunogenicity by releasing tumor antigens and Damage Associated Molecular Patterns (DAMPs). This is followed immediately by (2) injection of our proprietary immunostimulant, N-dihydro-acetylglucosamine (GC), into the laser-treated region to stimulate antigen presenting cells. These two steps work synergistically to enhance the systemic anti-tumor T cell response which is capable of eliminating both primary and metastatic cancers in some patients with advanced, stage III/IV, breast cancer with minimal toxicity. Our approach has the unique benefits of stimulating an immune response against a wide array of tumor antigens, and thus the potential to induce a strong, comprehensive and long-term anti-tumor protection in patients with minimal costs. Following early data showing efficacy in breast cancer patients, a multi-center, randomized clinical trial is currently underway in South America to consolidate the findings

Strong protection induced by an experimental DIVA subunit vaccine against bluetongue virus serotype 8 in cattle.

PubMed

Anderson, Jenna; Hägglund, Sara; Bréard, Emmanuel; Riou, Mickaël; Zohari, Siamak; Comtet, Loic; Olofson, Ann-Sophie; Gélineau, Robert; Martin, Guillaume; Elvander, Marianne; Blomqvist, Gunilla; Zientara, Stéphan; Valarcher, Jean Francois

2014-11-20

Bluetongue virus (BTV) infections in ruminants pose a permanent agricultural threat since new serotypes are constantly emerging in new locations. Clinical disease is mainly observed in sheep, but cattle were unusually affected during an outbreak of BTV seroype 8 (BTV-8) in Europe. We previously developed an experimental vaccine based on recombinant viral protein 2 (VP2) of BTV-8 and non-structural proteins 1 (NS1) and NS2 of BTV-2, mixed with an immunostimulating complex (ISCOM)-matrix adjuvant. We demonstrated that bovine immune responses induced by this vaccine were as good or superior to those induced by a classic commercial inactivated vaccine. In this study, we evaluated the protective efficacy of the experimental vaccine in cattle and, based on the detection of VP7 antibodies, assessed its DIVA compliancy following virus challenge. Two groups of BTV-seronegative calves were subcutaneously immunized twice at a 3-week interval with the subunit vaccine (n=6) or with adjuvant alone (n=6). Following BTV-8 challenge 3 weeks after second immunization, controls developed viremia and fever associated with other mild clinical signs of bluetongue disease, whereas vaccinated animals were clinically and virologically protected. The vaccine-induced protection was likely mediated by high virus-neutralizing antibody titers directed against VP2 and perhaps by cellular responses to NS1 and NS2. T lymphocyte responses were cross-reactive between BTV-2 and BTV-8, suggesting that NS1 and NS2 may provide the basis of an adaptable vaccine that can be varied by using VP2 of different serotypes. The detection of different levels of VP7 antibodies in vaccinated animals and controls after challenge suggested a compliancy between the vaccine and the DIVA companion test. This BTV subunit vaccine is a promising candidate that should be further evaluated and developed to protect against different serotypes. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

New Vaccines for the World's Poorest People.

PubMed

Hotez, Peter J; Bottazzi, Maria Elena; Strych, Ulrich

2016-01-01

The 2000 Millennium Development Goals helped stimulate the development of life-saving childhood vaccines for pneumococcal and rotavirus infections while greatly expanding coverage of existing vaccines. However, there remains an urgent need to develop new vaccines for HIV/AIDS, malaria, and tuberculosis, as well as for respiratory syncytial virus and those chronic and debilitating (mostly parasitic) infections known as neglected tropical diseases (NTDs). The NTDs represent the most common diseases of people living in extreme poverty and are the subject of this review. The development of NTD vaccines, including those for hookworm infection, schistosomiasis, leishmaniasis, and Chagas disease, is being led by nonprofit product development partnerships (PDPs) working in consortia of academic and industrial partners, including vaccine manufacturers in developing countries. NTD vaccines face unique challenges with respect to their product development and manufacture, as well as their preclinical and clinical testing. We emphasize global efforts to accelerate the development of NTD vaccines and some of the hurdles to ensuring their availability to the world's poorest people.

Psychological factors associated with uptake of the childhood influenza vaccine and perception of post-vaccination side-effects: A cross-sectional survey in England.

PubMed

Smith, Louise E; Webster, Rebecca K; Weinman, John; Amlôt, Richard; Yiend, Jenny; Rubin, G James

2017-04-04

To identify predictors of: uptake of the childhood influenza vaccine in the 2015-2016 influenza season, parental perceptions of side-effects from the influenza vaccine and intention to vaccinate one's child for influenza in the 2016-2017 influenza season. Cross-sectional online survey. Data were collected in England shortly after the end of the 2015-2016 immunization campaign. 1001 parents or guardians of children aged between two and seven. Self-reported uptake of the childhood influenza vaccine in the 2015-2016 influenza season, perception of side-effects from the influenza vaccine and intention to vaccinate one's child in the 2016-2017 influenza season. Self-reported uptake of the childhood influenza vaccine was 52.8%. Factors strongly positively associated with uptake included the child having previously been vaccinated against influenza, perceiving the vaccine to be effective and perceiving the child to be susceptible to flu. Factors strongly negatively associated with uptake included perceiving the vaccine to be unsafe, to cause short-term side-effects or long-term health problems and believing that yearly vaccination may overload the immune system. Predictors of intended vaccine uptake in 2016-2017 were similar. Participants who perceived side-effects after the 2015-2016 vaccination reported being less likely to vaccinate their child next year. Side-effects were more likely to be reported in first-born children, by participants who knew another child who had side-effects, those who thought that the vaccine would interact with medication that the child was currently taking, and those who believed the vaccine causes short-term side-effects. Perceptions about the childhood influenza vaccine show strong associations with uptake, intended uptake and perception of side-effects. Attempts to improve uptake rates from their current low levels must address these perceptions. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Synthetic Self-Adjuvanting Glycopeptide Cancer Vaccines

NASA Astrophysics Data System (ADS)

Payne, Richard; McDonald, David; Byrne, Scott

2015-10-01

Due to changes in glycosyltransferase expression during tumorigenesis, the glycoproteins of cancer cells often carry highly truncated carbohydrate chains compared to those on healthy cells. These glycans are known as tumor-associated carbohydrate antigens, and are prime targets for use in vaccines for the prevention and treatment of cancer. Herein, we review the state-of-the-art in targeting the immune system towards tumor-associated glycopeptide antigens via synthetic self adjuvanting vaccines, in which the antigenic and adjuvanting moieties of the vaccines are present in the same molecule. The majority of the self-adjuvanting glycopeptide cancer vaccines reported to date employ antigens from mucin 1, a protein which is highly over-expressed and aberrantly glycosylated in many forms of cancer. The adjuvants used in these vaccines predominantly include lipopeptide- or lipoamino acid-based TLR2 agonists, although studies investigating stimulation of TLR9 and TLR4 are also discussed. Most of these adjuvants are highly lipophilic, and, upon conjugation to antigenic peptides, provide amphiphilic vaccine molecules. The amphiphilic nature of these vaccine constructs can lead to the formation of higher-order structures by vaccines in solution, which are likely to be important for their efficacy in vivo.

Evaluation of the persistence of vaccine-induced protection with human vaccines.

PubMed

Vidor, E

2010-01-01

The persistence of protection induced by vaccines is a key aspect of the implementation of human vaccination policies, particularly for ageing populations. At the time of initial licensure, the duration of protection induced by a vaccine is generally only documented by longitudinal follow up of cohorts of subjects enrolled in the pre-licensure trials over a period of 1-5 years. The follow up of these cohorts provides two types of data: antibody kinetics (or another clinically relevant immunological parameter) over time and the disease incidence. Generally, the latter trials, if implemented during the pre-licensure period, are designed to follow-up cohorts in order to demonstrate vaccine efficacy above the minimal level required for the license. For vaccines already licensed, additional tools exist. The use of immunological surrogate markers of protection is a practical way to monitor the duration of protection. Measuring the persistence of circulating antibodies is widely used in human vaccines. For several vaccines, observed data have allowed the creation of mathematical models to predict the antibody persistence over periods of time longer than those effectively documented. Clinical trials assessing the capacity of the immune system to mount a quick anamnestic response upon re-stimulation a long time after initial priming (measurement of immune memory) is also a tool employed to document the duration of protection. The waning of protection can also be demonstrated by an increase of disease incidence in the subsequent 'time-to-last-vaccine administration' age segments. Seroprevalence studies in a given age group of people that were vaccinated under real-life conditions are another way to document the persistence of protection. Finally, case-control studies in outbreak situations or in situations of persisting endemicity can also be used to document the persistence of the vaccine efficacy. All of these tools are used in the development of new vaccines, and also

Towards a human oral vaccine for anthrax: the utility of a Salmonella Typhi Ty21a-based prime-boost immunization strategy.

PubMed

Baillie, Leslie W J; Rodriguez, Ana L; Moore, Stephen; Atkins, Helen S; Feng, Chiguang; Nataro, James P; Pasetti, Marcela F

2008-11-11

We previously demonstrated the ability of an orally administered attenuated Salmonella enterica serovar Typhimurium strain expressing the protective antigen (PA) of Bacillus anthracis to confer protection against lethal anthrax aerosol spore challenge [Stokes MG, Titball RW, Neeson BN, et al. Oral administration of a Salmonella enterica-based vaccine expressing Bacillus anthracis protective antigen confers protection against aerosolized B. anthracis. Infect Immun 2007;75(April (4)):1827-34]. To extend the utility of this approach to humans we constructed variants of S. enterica serovar Typhi Ty21a, an attenuated typhoid vaccine strain licensed for human use, which expressed and exported PA via two distinct plasmid-based transport systems: the Escherichia coli HlyA haemolysin and the S. Typhi ClyA export apparatus. Murine immunogenicity studies confirmed the ability of these constructs, especially Ty21a expressing the ClyA-PA fusion protein, to stimulate strong PA-specific immune responses following intranasal immunization. These responses were further enhanced by a subsequent boost with either parenterally delivered recombinant PA or the licensed US human alum-adsorbed anthrax vaccine (AVA). Anthrax toxin neutralizing antibody responses using this prime-boost regimen were rapid, vigorous and broad in nature. The results of this study demonstrate the feasibility of employing a mucosal prime with a licensed Salmonella Typhi vaccine strain followed by a parenteral protein boost to stimulate rapid protective immunity against anthrax.

CHEMOKINE RECEPTOR 7 (CCR7)-EXPRESSION AND IFNγ PRODUCTION DEFINE VACCINE-SPECIFIC CANINE T CELL SUBSETS

PubMed Central

Hartley, Ashley N.; Tarleton, Rick L.

2015-01-01

Canines suffer from and serve as strong translational animals models for many immunological disorders and infectious diseases. Routine vaccination has been a mainstay of protecting dogs through the stimulation of robust antibody responses and expansion of memory T cell populations. Commercially available reagents and described techniques are limited for identifying and characterizing canine T cell subsets and evaluating T cell-specific effector function. To define reagents for delineating naïve versus activated T cells and identify antigen-specific T cells, we tested anti-human and anti-bovine T-cell specific cell surface marker reagents for cross-reactivity with canine peripheral blood mononuclear cells (PBMCs. Both CD4+ and CD8+ T cells from healthy canine donors showed reactivity to CCL19-Ig, a CCR7 ligand, and coexpression with CD62L. An in vitro stimulation with concanavalin A validated downregulation of CCR7 and CD62L expression on stimulated healthy control PBMCs, consistent with an activated T cell phenotype. Anti-IFNγ antibodies identified antigen-specific IFNγ-producing CD4+ and CD8+ T cells upon in vitro vaccine antigen PBMC stimulation. PBMC isolation within 24 hours of sample collection allowed for efficient cell recovery and accurate T cell effector function characterization. These data provide a reagent and techniques platform via flow cytometry for identifying canine T cell subsets and characterizing circulating antigen-specific canine T cells for potential use in diagnostic and field settings. PMID:25758065

Influence of strong and weak hydrogen bonds in ices on stimulated Raman scattering.

PubMed

Li, Tianyu; Li, Fangfang; Li, Zhanlong; Sun, Chenglin; Tong, Junhong; Fang, Wenhui; Men, Zhiwei

2016-03-15

Stimulated Raman scattering (SRS) in liquid water and ice Ih using Nd:YAG laser is investigated. The spectrum of backward SRS (BSRS) in water is acquired. The spectrum shows an unexpected SRS peak at around 3453  cm(-1) besides the normal peak, which is similar to the spontaneous Raman spectrum of ice VII. The ice VII phase will be formed by laser-induced shock compression in liquid water. Simultaneously, unlike the spontaneous Raman spectrum, the pre-resonance SRS of ice Ih at around 3110 and 3210  cm(-1) is observed. The Raman peaks appeared in liquid water and ice Ih are attributed to the effect of strong and weak hydrogen bonds (H bonds), which should be ubiquitous in other ice phases.

Vaccines and immunization strategies for dengue prevention

PubMed Central

Liu, Yang; Liu, Jianying; Cheng, Gong

2016-01-01

Dengue is currently the most significant arboviral disease afflicting tropical and sub-tropical countries worldwide. Dengue vaccines, such as the multivalent attenuated, chimeric, DNA and inactivated vaccines, have been developed to prevent dengue infection in humans, and they function predominantly by stimulating immune responses against the dengue virus (DENV) envelope (E) and nonstructural-1 proteins (NS1). Of these vaccines, a live attenuated chimeric tetravalent DENV vaccine developed by Sanofi Pasteur has been licensed in several countries. However, this vaccine renders only partial protection against the DENV2 infection and is associated with an unexplained increased incidence of hospitalization for severe dengue disease among children younger than nine years old. In addition to the virus-based vaccines, several mosquito-based dengue immunization strategies have been developed to interrupt the vector competence and effectively reduce the number of infected mosquito vectors, thus controlling the transmission of DENV in nature. Here we summarize the recent progress in the development of dengue vaccines and novel immunization strategies and propose some prospective vaccine strategies for disease prevention in the future. PMID:27436365

Vaccine platforms to control Lassa fever.

PubMed

Lukashevich, Igor S; Pushko, Peter

2016-09-01

Lassa virus (LASV), the most prominent human pathogen of the Arenaviridae, is transmitted to humans from infected rodents and can cause Lassa Fever (LF). The sizeable disease burden in West Africa, numerous imported LF cases worldwide, and the possibility that LASV can be used as an agent of biological warfare make a strong case for vaccine development. There are no licensed LASV vaccines and the antiviral treatment is limited to an off-label use of ribavirin that is only partially effective. LASV vaccine development is hampered by high cost of biocontainment requirement, the absence of appropriate small animal models, genetic diversity of LASV species, and by high HIV-1 prevalence in LASV endemic areas. Over the past 15 years several vaccine platforms have been developed. Natural history of LASV and pathogenesis of the disease provide strong justification for replication-competent (RC) vaccine as one of the most feasible approaches to control LF. Development of LASV vaccine candidates based on reassortant, recombinant, and alphavirus replicon technologies is covered in this review. Expert commentary: Two lead RC vaccine candidates, reassortant ML29 and recombinant VSV/LASV, have been successfully tested in non-human primates and have been recommended by international vaccine experts for rapid clinical development. Both platforms have powerful molecular tools to further secure safety, improve immunogenicity, and cross-protection. These platforms are well positioned to design multivalent vaccines to protect against all LASV strains citculatrd in West Africa. The regulatory pathway of Candid #1, the first live-attenuated arenaviral vaccine against Argentine hemorrhagic, will be a reasonable guideline for LASV vaccine efficacy trials.

Association of the expression of Th cytokines with peripheral CD4 and CD8 lymphocyte subsets after vaccination with FMD vaccine in Holstein young sires.

PubMed

Yang, Ling; Liu, Zhichao; Li, Jianbin; He, Kaili; Kong, Lingna; Guo, Runqing; Liu, Wenjiao; Gao, Yundong; Zhong, Jifeng

2018-05-25

High immune response (HIR) cows have a balanced and robust host defense and lower disease incidence, and immune response is more important to consider for selecting young sires than for selecting cows. The protective immune response against foot-and-mouth disease (FMD) virus infection is T-cell-independent in an animal experimental model. However, there is no convenient method to select young sires with a HIR to FMD virus. In this study, 39 healthy Holstein young sires were vaccinated with the trivalent (A, O and Asia 1) FMD vaccine, and T-lymphocyte subsets in peripheral blood lymphocytes (PBLs) were detected using flow cytometric analysis before and after vaccination. The expression of interferon-gamma (IFN-γ), interleukin-2 (IL-2), IL-4, and IL-6 mRNA in PBLs was analyzed after stimulation by lipopolysaccharide (LPS) or Concanavalin A (ConA) after vaccination. According to the percentage of CD4 + lymphocyte and CD4/CD8 ratio after vaccination for selecting the HIR young sires, the results showed that the percentages of CD3 + , CD4 + , CD3 + CD4 + lymphocytes and the CD4/CD8 ratio in the HIR group were higher compared to those in the medium immune response (MIR) and low immune response (LIR) groups before vaccination. Additionally, the percentage of CD4 + lymphocytes and the CD4/CD8 ratio after vaccination were positively associated with the expression level of IFN-γ mRNA in the PBLs after stimulation by LPS. In conclusion, the in vitro expression level of IFN-γ mRNA in the PBLs stimulated by LPS may serve as a parameter for selecting young sires with a HIR to FMD virus. Copyright © 2018 Elsevier Ltd. All rights reserved.

Next generation vaccines.

PubMed

Riedmann, Eva M

2011-07-01

In February this year, about 100 delegates gathered for three days in Vienna (Austria) for the Next Generation Vaccines conference. The meeting held in the Vienna Hilton Hotel from 23rd-25th February 2011 had a strong focus on biotech and industry. The conference organizer Jacob Fleming managed to put together a versatile program ranging from the future generation of vaccines to manufacturing, vaccine distribution and delivery, to regulatory and public health issues. Carefully selected top industry experts presented first-hand experience and shared solutions for overcoming the latest challenges in the field of vaccinology. The program also included several case study presentations on novel vaccine candidates in different stages of development. An interactive pre-conference workshop as well as interactive panel discussions during the meeting allowed all delegates to gain new knowledge and become involved in lively discussions on timely, interesting and sometimes controversial topics related to vaccines.

“To each his own”: Discussions of vaccine decision-making in top parenting blogs

PubMed Central

Meleo-Erwin, Zoë; Basch, Corey; MacLean, Sarah A.; Scheibner, Courtney; Cadorett, Valerie

2017-01-01

ABSTRACT Although social media provides a way for people to congregate with like-minded others, it can also play a role in spreading misinformation about public health interventions. Previous research demonstrates that parents who use the Internet to gather information on vaccination are more likely to hold anti-vaccination beliefs. There has been little examination of vaccination decision-making discussions on parenting blogs. This study seeks to fill that gap. Posts and comments on the top 25 top parenting blogs were analyzed using a mixed-method approach. Comments were analyzed using deductive coding scheme that examined whether content areas of interest were present or absent in vaccination discussions. Posts were coded inductively using a thematic analysis. Posts and comments were further coded as strongly vaccine-discouraging, vaccine-ambivalent, or strongly vaccine-encouraging. Finally, posts were grouped by year of publication and comments were analyzed within each group to examine the evolution of vaccination decision-making discussions in the parenting blogosphere over the past decade. Fifty-two percent of posts were categorized as strongly vaccine-discouraging and were most commonly associated with expressions of individual liberty. Comments were nearly 3 times as likely to strongly discourage vaccination than to strongly encourage it. Comments on the oldest posts (2006–2009), were more likely to strongly discourage vaccination (p = 0.008), whereas comments on newer posts (2013–2015), were more likely to strongly encourage vaccination (p = 0.003). These findings suggest there is a need for public health professionals to understand the concerns being expressed in these forums, and develop innovative ways to dispel anti-vaccination myths, as these views may create obstacles in the meeting the goals of the public health agenda. PMID:28481675

Beyond empiricism: Informing vaccine development through innate immunity research

PubMed Central

Levitz, Stuart M.; Golenbock, Douglas T.

2012-01-01

Summary While a great public heath success, vaccines provide suboptimal protection in some patient populations and are not available to protect against many infectious diseases. Insights from innate immunity research have led to a better understanding of how existing vaccines work and informed vaccine development. New adjuvants and delivery systems are being designed based upon their capacity to stimulate innate immune sensors and target antigens to dendritic cells, the cells responsible for initiating adaptive immune responses. Incorporating these adjuvants and delivery systems in vaccines can beneficially alter the quantitative and qualitative nature of the adaptive immune response resulting in enhanced protection. PMID:22424235

Neonatal BCG vaccination is associated with enhanced T-helper 1 immune responses to heterologous infant vaccines

PubMed Central

Libraty, Daniel H.; Zhang, Lei; Woda, Marcia; Acosta, Luz P.; Obcena, AnaMae; Brion, Job D.; Capeding, Rosario Z.

2014-01-01

Neonatal Bacille Calmette Guérin (BCG) vaccination has been reported to have beneficial effects beyond preventing infantile tuberculous meningitis and miliary disease. We hypothesized that BCG vaccine given at birth would enhance T-helper 1 (Th1) immune responses to the first vaccines given later in infancy. We conducted a nested case-control study of neonatal BCG vaccination and its heterologous Th1 immune effects in 2–3 months old infants. BCG vaccination at birth was associated with an increased frequency of interferon-γ (IFN-γ) producing spot-forming cells (SFC) to tetanus toxoid 2–3 months later. The frequency of IFN-γ producing SFC to polioviruses 1–3 also trended higher among infants who received BCG vaccination at birth. The frequency of IFN-γ+/tumor necrosis factor-α (TNF-α)+CD45RO+CD4+ T-cells upon stimulation with phorbol myristate acetate (PMA)/Ionomycin was higher in 2–3 months old infants who received BCG vaccination at birth compared to those who did not. The circulating frequency of forkhead box P3 (FoxP3)+ CD45RO+ regulatory CD4+ T-cells also trended lower in these infants. Neonatal BCG vaccination is associated with heterologous Th1 immune effects 2–3 months later. PMID:24611083

Neonatal BCG vaccination is associated with enhanced T-helper 1 immune responses to heterologous infant vaccines.

PubMed

Libraty, Daniel H; Zhang, Lei; Woda, Marcia; Acosta, Luz P; Obcena, Anamae; Brion, Job D; Capeding, Rosario Z

2014-01-01

Neonatal Bacille Calmette Guérin (BCG) vaccination has been reported to have beneficial effects beyond preventing infantile tuberculous meningitis and miliary disease. We hypothesized that BCG vaccine given at birth would enhance T-helper 1 (Th1) immune responses to the first vaccines given later in infancy. We conducted a nested case-control study of neonatal BCG vaccination and its heterologous Th1 immune effects in 2-3 months old infants. BCG vaccination at birth was associated with an increased frequency of interferon-γ (IFN-γ) producing spot-forming cells (SFC) to tetanus toxoid 2-3 months later. The frequency of IFN-γ producing SFC to polioviruses 1-3 also trended higher among infants who received BCG vaccination at birth. The frequency of IFN-γ+/tumor necrosis factor-α (TNF-α)+CD45RO+CD4+ T-cells upon stimulation with phorbol myristate acetate (PMA)/Ionomycin was higher in 2-3 months old infants who received BCG vaccination at birth compared to those who did not. The circulating frequency of forkhead box P3 (FoxP3)+ CD45RO+ regulatory CD4+ T-cells also trended lower in these infants. Neonatal BCG vaccination is associated with heterologous Th1 immune effects 2-3 months later.

Managing the effect of TRIPS on availability of priority vaccines.

PubMed Central

Milstien, Julie; Kaddar, Miloud

2006-01-01

The stated purpose of intellectual property protection is to stimulate innovation. The Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS) requires all Members of the World Trade Organization (WTO) to enact national laws conferring minimum standards of intellectual property protection by certain deadlines. Critics of the Agreement fear that such action is inconsistent with ensuring access to medicines in the developing world. A WHO convened meeting on intellectual property rights and vaccines in developing countries, on which this paper is based, found no evidence that TRIPS has stimulated innovation in developing market vaccine development (where markets are weak) or that protection of intellectual property rights has had a negative effect on access to vaccines. However, access to future vaccines in the developing world could be threatened by compliance with TRIPS. The management of such threats requires adherence of all countries to the Doha Declaration on TRIPS, and the protections guaranteed by the Agreement itself, vigilance on TRIPS-plus elements of free trade agreements, developing frameworks for licensing and technology transfer, and promoting innovative vaccine development in developing countries. The role of international organizations in defining best practices, dissemination of information, and monitoring TRIPS impact will be crucial to ensuring optimal access to priority new vaccines for the developing world. PMID:16710544

HPV vaccination uptake among Cambodian mothers.

PubMed

Taylor, Victoria M; Burke, Nancy; Do, Hoai; Liu, Qi; Yasui, Yutaka; Bastani, Roshan

2012-03-01

Women of Southeast Asian descent have higher cervical cancer incidence rates than any other group. Widespread use of HPV vaccination could prevent up to 70% of cervical cancers. There is little published information addressing HPV vaccination uptake among Asian Americans. We conducted a survey of Cambodian women with daughters who were age-eligible for HPV vaccination. Survey items addressed HPV vaccination barriers, facilitators, and uptake. Only 26% of the survey participants reported any of their age-eligible daughters had received vaccination, and only 40% reported a previous physician recommendation for vaccination. Higher levels of vaccine uptake were strongly associated with having received a doctor's recommendation for vaccination (p < 0.001) and having asked a doctor for vaccination (p = 0.002). HPV vaccine uptake was relatively low in our Cambodian study group. Educational initiatives should encourage health care providers who serve Cambodian families to recommend HPV vaccination and empower Cambodian mothers to ask their daughters' doctors for vaccination.

Association of both consistency and strength of self-reported clinician recommendation for HPV vaccination and HPV vaccine uptake among 11- to 12-year-old children.

PubMed

Finney Rutten, Lila J; St Sauver, Jennifer L; Beebe, Timothy J; Wilson, Patrick M; Jacobson, Debra J; Fan, Chun; Breitkopf, Carmen Radecki; Vadaparampil, Susan T; MacLaughlin, Kathy L; Jacobson, Robert M

2017-10-27

We tested the hypotheses that consistency and strength of clinician recommendation of the human papillomavirus (HPV) vaccination would be associated with vaccine delivery rates. From October 2015 through January 2016, we conducted a survey of primary care clinicians (n=227) in Southeastern Minnesota to evaluate clinician behaviors regarding HPV vaccination. The survey response rate was 41.0% (51 clinical sites). We used the Rochester Epidemiology Project, a clinical data linkage infrastructure, to ascertain clinical site-level HPV vaccination rates. We examined associations of clinician self-reports of both the consistency and strength of their recommendations for HPV vaccination for patients aged 11-12years (n=14,406) with site-level vaccination rates. The majority of clinicians reported consistently (always or usually) recommending the HPV vaccine to females (79.0%) and to males (62.2%); 71.9% of clinicians reported strongly recommending the vaccine to females while 58.6% reported strongly recommending to males. Consistency and strength of recommending the HPV vaccine was significantly higher among those practicing in pediatrics and board certified in pediatrics compared to family medicine. Higher rates of initiation (1 dose) [Incidence Rate Ratio (IRR)=1.05; 95% CI (1.01-1.09)] and completion (3 doses) [IRR=1.08; 95% CI (1.02-1.13)] were observed among clinical sites where, on average, clinicians more frequently reported always or usually recommending the vaccine for females compared to sites where, on average, clinicians reported recommending the vaccine less frequently. Similarly, higher rates of initiation [IRR=1.03; 95% CI (1.00-1.06)] and completion [IRR=1.04; CI (1.00, 1.08)] were observed among sites where clinicians reported strongly recommending the vaccine to females more frequently compared to sites where, on average, clinicians reported strongly recommending the HPV vaccine less frequently; similar associations were observed for male initiation [IRR

Impact of Virginia's School-Entry Vaccine Mandate on Human Papillomavirus Vaccination Among 13-17-Year-Old Females.

PubMed

Pierre-Victor, Dudith; Page, Timothy F; Trepka, Mary Jo; Stephens, Dionne P; Li, Tan; Madhivanan, Purnima

2017-03-01

The link between human papillomavirus (HPV) and anogenital cancers is well established in the literature. Many states have passed laws requiring funding for HPV education or vaccination. Mandatory HPV vaccination policies have been considered and passed in several states; yet their effectiveness has not been evaluated. This study sought to assess the impact of Virginia's HPV vaccine mandate for school-entry on HPV vaccine uptake among females aged 13-17 years. Data from the National Immunization Survey-Teen for the 2008-2012 period were used, and 3,203 adolescent females were included in the analysis. We performed difference-in-differences estimation and logistic regression with a policy and period interaction term. Virginia was considered the treatment state, and South Carolina and Tennessee were the comparison states to account for nonpolicy factors that may have affected vaccination rates during the time period considered in the analysis. There was no evidence of an effect of Virginia's HPV vaccine mandate for school-entry on vaccination rates or on physician vaccination recommendation using either the difference-by-differences analysis or the policy and period interaction term in the logistic regression. Physician recommendation was the factor most strongly associated with vaccination in the Virginia-South Carolina analysis (adjusted odds ratio [aOR] = 9.33; 95% confidence interval [CI]: 6.11-14.3) and in the Virginia-Tennessee analysis (aOR = 9.33; 95% CI: 6.11-14.3). Study findings suggest that Virginia's HPV vaccine mandate for school-entry did not lead to a significant increase in HPV vaccination among adolescent females or physician recommendations. However, physician recommendation was the factor most strongly associated with vaccination.

Safety and immunogenecity of a live attenuated Rift Valley fever vaccine (CL13T) in camels.

PubMed

Daouam, S; Ghzal, F; Naouli, Y; Tadlaoui, K O; Ennaji, M M; Oura, C; El Harrak, M

2016-07-26

Rift Valley fever is an emerging zoonotic viral disease, enzootic and endemic in Africa and the Arabian Peninsula, which poses a significant threat to both human and animal health. The disease is most severe in ruminants causing abortions in pregnant animals, especially sheep animals and high mortality in young populations. High mortality rates and severe clinical manifestation have also been reported among camel populations in Africa, to attend however none of the currently available live vaccines against RVF have been tested for safety and efficacy in this species. In this study, the safety and efficacy (through a neutralizing antibody response) of the thermostable live attenuated RVF CL13T vaccine were evaluated in camels in two different preliminary experiments involving 16 camels, (that 12 camels and 4 pregnant camels). The study revealed that the CL13T vaccine was safe to use in camels and no abortions or teratogenic effects were observed. The single dose of the vaccine stimulated a strong and long-lasting neutralizing antibody response for up to 12 months. The presence of neutralization antibodies is likely to correlate with protection; however protection would need to be confirmed by challenge experiments using the virulent RVF virus.

TLR-adjuvanted nanoparticle vaccines differentially influence the quality and longevity of responses to malaria antigen Pfs25.

PubMed

Thompson, Elizabeth A; Ols, Sebastian; Miura, Kazutoyo; Rausch, Kelly; Narum, David L; Spångberg, Mats; Juraska, Michal; Wille-Reece, Ulrike; Weiner, Amy; Howard, Randall F; Long, Carole A; Duffy, Patrick E; Johnston, Lloyd; O'Neil, Conlin P; Loré, Karin

2018-05-17

Transmission-blocking vaccines (TBVs) are considered an integral element of malaria eradication efforts. Despite promising evaluations of Plasmodium falciparum Pfs25-based TBVs in mice, clinical trials have failed to induce robust and long-lived Ab titers, in part due to the poorly immunogenic nature of Pfs25. Using nonhuman primates, we demonstrate that multiple aspects of Pfs25 immunity were enhanced by antigen encapsulation in poly(lactic-co-glycolic acid)-based [(PLGA)-based] synthetic vaccine particles (SVP[Pfs25]) and potent TLR-based adjuvants. SVP[Pfs25] increased Ab titers, Pfs25-specific plasmablasts, circulating memory B cells, and plasma cells in the bone marrow when benchmarked against the clinically tested multimeric form Pfs25-EPA given with GLA-LSQ. SVP[Pfs25] also induced the first reported Pfs25-specific circulating Th1 and Tfh cells to our knowledge. Multivariate correlative analysis indicated several mechanisms for the improved Ab responses. While Pfs25-specific B cells were responsible for increasing Ab titers, T cell responses stimulated increased Ab avidity. The innate immune activation differentially stimulated by the adjuvants revealed a strong correlation between type I IFN polarization, induced by R848 and CpG, and increased Ab half-life and longevity. Collectively, the data identify ways to improve vaccine-induced immunity to poorly immunogenic proteins, both by the choice of antigen and adjuvant formulation, and highlight underlying immunological mechanisms.

Acellular Pertussis Vaccines and Pertussis Resurgence: Revise or Replace?

PubMed Central

Ausiello, Clara Maria

2014-01-01

ABSTRACT The resurgence of pertussis (whooping cough) in countries with high vaccination coverage is alarming and invites reconsideration of the use of current acellular pertussis (aP) vaccines, which have largely replaced the old, reactogenic, whole-cell pertussis (wP) vaccine. Some drawbacks of these vaccines in terms of limited antigenic composition and early waning of antibody levels could be anticipated by the results of in-trial or postlicensure human investigations of B- and T-cell responses in aP versus wP vaccine recipients or unvaccinated, infected children. Recent data in experimental models, including primates, suggest that generation of vaccines capable of a potent, though regulated, stimulation of innate immunity driving effective, persistent adaptive immune responses against Bordetella pertussis infection should be privileged. Adjuvants that skew Th1/Th17 responses or new wP (detoxified or attenuated) vaccines should be explored. Nonetheless, the high merits of the current aP vaccines in persuading people to resume vaccination against pertussis should not be forgotten. PMID:24917600

HPV vaccination prevalence, parental barriers and motivators to vaccinating children in Hawai'i.

PubMed

Dela Cruz, May Rose Isnec; Braun, Kathryn L; Tsark, Jo Ann Umilani; Albright, Cheryl Lynn; Chen, John J

2018-05-10

To determine the prevalence and barriers to human papillomavirus (HPV) vaccine uptake among 11-18 year olds in the Hawai'i's four major ethnic groups-Native Hawaiians, Filipinos, Japanese, and Caucasians. A telephone survey assessed parents' knowledge of HPV and the HPV vaccine, status of their child's HPV vaccine uptake, variables operationalizing the Health Belief Model, and barriers and motivators to uptake. Across the groups, 799 parents completed the survey. About 35% of daughters and 19% of sons had received all three shots. Although ethnic differences in vaccine uptake were seen in bivariate analysis (with significantly lower uptake in Filipino youth), in multivariable logistic regression analysis, only Caucasian parents were significantly less likely to start their sons on the HPV vaccine series compared with Japanese parents (reference group). Having heard about the vaccine, believing in its effectiveness, and older age of the child were also associated with vaccine uptake. Motivators for HPV vaccination were physician's recommendation and wanting to protect one's child. The primary barrier to uptake was lack of knowledge about the vaccine. Findings reinforce the fact that a physician's recommendation and receipt of information about the vaccine are strong motivators for parents to vaccinate their children, regardless of ethnicity.

Parents’ perceptions of provider communication regarding adolescent vaccines

PubMed Central

Dempsey, Amanda F.; Pyrzanowski, Jennifer; Lockhart, Steven; Campagna, Elizabeth; Barnard, Juliana; O'Leary, Sean T.

2016-01-01

ABSTRACT Strong provider recommendations for adolescent vaccines are critical for achieving high vaccination levels.  However, little is known about parents’ preferred provider communication strategies for adolescent vaccines in general, and for human papillomavirus (HPV) vaccines specifically. We performed a cross-sectional survey of 800 parents of 9-14 year olds in April 2014 to assess current adolescent vaccine communication practices by providers, parents’ preferred HPV vaccine-specific communication strategies, and the association of these two outcomes with experiential, attitudinal and demographic characteristics.  Among the 356 parents in the study (response rate 48%), HPV vaccines were reported as less likely to have been “very strongly” recommended by their adolescent’s provider (39%) than other adolescent-targeted vaccines (45%-59%, <0.05 for all comparisons).  Receiving a very strong recommendation for HPV vaccines was associated with a higher likelihood of vaccine receipt (71% versus 39%, p<0.001), or among those not yet vaccinated, increased likelihood of positive vaccination intentions (82% vs. 60%, p = 0.015).  Nearly all parents (87%) reported that, if available, they would use a website providing personalized HPV vaccine-related materials before their adolescent’s next check-up, and other technology-based communications were also endorsed by the majority of parents.   From these data we conclude that parents received weaker recommendations for HPV vaccines than other adolescent vaccines, and that most parents want additional HPV vaccine-related materials, preferably delivered using a variety of technology-based modalities which is not their providers’ current practice. PMID:27078515

A novel, disruptive vaccination technology: self-adjuvanted RNActive(®) vaccines.

PubMed

Kallen, Karl-Josef; Heidenreich, Regina; Schnee, Margit; Petsch, Benjamin; Schlake, Thomas; Thess, Andreas; Baumhof, Patrick; Scheel, Birgit; Koch, Sven D; Fotin-Mleczek, Mariola

2013-10-01

Nucleotide based vaccines represent an enticing, novel approach to vaccination. We have developed a novel immunization technology, RNActive(®) vaccines, that have two important characteristics: mRNA molecules are used whose protein expression capacity has been enhanced by 4 to 5 orders of magnitude by modifications of the nucleotide sequence with the naturally occurring nucleotides A (adenosine), G (guanosine), C (cytosine), U (uridine) that do not affect the primary amino acid sequence. Second, they are complexed with protamine and thus activate the immune system by involvement of toll-like receptor (TLR) 7. Essentially, this bestows self-adjuvant activity on RNActive(®) vaccines. RNActive(®) vaccines induce strong, balanced immune responses comprising humoral and cellular responses, effector and memory responses as well as activation of important subpopulations of immune cells, such as Th1 and Th2 cells. Pre-germinal center and germinal center B cells were detected in human patients upon vaccination. RNActive(®) vaccines successfully protect against lethal challenges with a variety of different influenza strains in preclinical models. Anti-tumor activity was observed preclinically under therapeutic as well as prophylactic conditions. Initial clinical experiences suggest that the preclinical immunogenicity of RNActive(®) could be successfully translated to humans.

Detecting T-cell reactivity to whole cell vaccines

PubMed Central

Brusic, Ana; Hainz, Ursula; Wadleigh, Martha; Neuberg, Donna; Su, Mei; Canning, Christine M.; DeAngelo, Daniel J.; Stone, Richard M.; Lee, Jeng-Shin; Mulligan, Richard C.; Ritz, Jerome; Dranoff, Glenn; Sasada, Tetsuro; Wu, Catherine J.

2012-01-01

BCR-ABL+ K562 cells hold clinical promise as a component of cancer vaccines, either as bystander cells genetically modified to express immunostimulatory molecules, or as a source of leukemia antigens. To develop a method for detecting T-cell reactivity against K562 cell-derived antigens in patients, we exploited the dendritic cell (DC)-mediated cross-presentation of proteins generated from apoptotic cells. We used UVB irradiation to consistently induce apoptosis of K562 cells, which were then fed to autologous DCs. These DCs were used to both stimulate and detect antigen-specific CD8+ T-cell reactivity. As proof-of-concept, we used cross-presented apoptotic influenza matrix protein-expressing K562 cells to elicit reactivity from matrix protein-reactive T cells. Likewise, we used this assay to detect increased anti-CML antigen T-cell reactivity in CML patients that attained long-lasting clinical remissions following immunotherapy (donor lymphocyte infusion), as well as in 2 of 3 CML patients vaccinated with lethally irradiated K562 cells that were modified to secrete high levels of granulocyte macrophage colony-stimulating factor (GM-CSF). This methodology can be readily adapted to examine the effects of other whole tumor cell-based vaccines, a scenario in which the precise tumor antigens that stimulate immune responses are unknown. PMID:23170257

Aluminum hydroxide colloid vaccine encapsulated in yeast shells with enhanced humoral and cellular immune responses.

PubMed

Liu, Hui; Jia, Zhenghu; Yang, Chengmao; Song, Mei; Jing, Zhe; Zhao, Yapu; Wu, Zhenzhou; Zhao, Liqing; Wei, Dongsheng; Yin, Zhinan; Hong, Zhangyong

2018-06-01

Aluminum salt (Alum) is one of the most important immune adjuvants approved for use in humans, however it is not suitable for vaccination against various chronic infectious diseases and cancers for not being able to induce cell-mediated (Th1) immunity. Here, we encapsulated an Alum colloid inside β-glucan particles (GPs), which are a type of natural particles derived from the yeast glucan shells, to prepare hybrid GP-Alum (GP-Al) adjuvant particles with a very uniform size of 2-4 μm. These hybrid particles can be used to load antigen proteins through a simple mixing procedure, and can be highly specifically targeted to antigen-presenting cells (APCs) and strongly activate dendritic cells (DCs) maturation and cytokine secretion. In an animal model, they elicit a strong Th1-biased immune response and extremely high antibody titer, and cause marked prophylactic and therapeutic effects against tumors. As Alum has been proven to be a safe adjuvant to induce strong humoral responses and β-glucans are safe for human use, this very uniform hybrid Alum particulate system could have important application as a vaccine carrier to stimulate humoral and cellular immune responses at the same time. Copyright © 2018 Elsevier Ltd. All rights reserved.

Eimeria maxima recombinant Gam82 gametocyte antigen vaccine protects against coccidiosis and augments humoral and cell-mediated immunity.

PubMed

Jang, Seung I; Lillehoj, Hyun S; Lee, Sung Hyen; Lee, Kyung Woo; Park, Myeong Seon; Cha, Sung-Rok; Lillehoj, Erik P; Subramanian, B Mohana; Sriraman, R; Srinivasan, V A

2010-04-09

Intestinal infection with Eimeria, the etiologic agent of avian coccidiosis, stimulates protective immunity to subsequent colonization by the homologous parasite, while cross-protection against heterologous species is poor. As a first step toward the development of a broad specificity Eimeria vaccine, this study was designed to assess a purified recombinant protein from Eimeria maxima gametocytes (Gam82) in stimulating immunity against experimental infection with live parasites. Following Gam82 intramuscular immunization and oral parasite challenge, body weight gain, fecal oocyst output, lesion scores, serum antibody response, and cytokine production were assessed to evaluate vaccination efficacy. Animals vaccinated with Gam82 and challenged with E. maxima showed lower oocyst shedding and reduced intestinal pathology compared with non-vaccinated and parasite-challenged animals. Gam82 vaccination also stimulated the production of antigen-specific serum antibodies and induced greater levels of IL-2 and IL-15 mRNAs compared with non-vaccinated controls. These results demonstrate that the Gam82 recombinant protein protects against E. maxima and augments humoral and cell-mediated immunity. Published by Elsevier Ltd.

Mucosal Vaccine Development Based on Liposome Technology

PubMed Central

Norling, Karin; Bally, Marta; Höök, Fredrik

2016-01-01

Immune protection against infectious diseases is most effective if located at the portal of entry of the pathogen. Hence, there is an increasing demand for vaccine formulations that can induce strong protective immunity following oral, respiratory, or genital tract administration. At present, only few mucosal vaccines are found on the market, but recent technological advancements and a better understanding of the principles that govern priming of mucosal immune responses have contributed to a more optimistic view on the future of mucosal vaccines. Compared to live attenuated vaccines, subcomponent vaccines, most often protein-based, are considered safer, more stable, and less complicated to manufacture, but they require the addition of nontoxic and clinically safe adjuvants to be effective. In addition, another limiting factor is the large antigen dose that usually is required for mucosal vaccines. Therefore, the combination of mucosal adjuvants with the recent progress in nanoparticle technology provides an attractive solution to these problems. In particular, the liposome technology is ideal for combining protein antigen and adjuvant into an effective mucosal vaccine. Here, we describe and discuss recent progress in nanoparticle formulations using various types of liposomes that convey strong promise for the successful development of the next generation of mucosal vaccines. PMID:28127567

λ-Carrageenan improves the antitumor effect of dendritic cellbased vaccine.

PubMed

Li, Jinyao; Aipire, Adila; Li, Jinyu; Zhu, Hongge; Wang, Yanping; Guo, Wenjia; Li, Xiaoqin; Yang, Jia; Liu, Chunling

2017-05-02

In this study, we investigated the effect of λ-carrageenan on the maturation and function of dendritic cells (DCs) and its adjuvant effect on DC-based vaccine. We found that λ-carrageenan dose-dependently decreased the endocytosis of DCs, promoted DC maturation and increased cytokine production through TLR4 mediated signaling pathway. λ-carrageenan treatment also enhanced the ability of DCs in the stimulating allogenic splenocyte proliferation. In TC-1 tumor mouse model, HPV peptides pulsed λ-carrageenan-DC (HPV-CGN-DC) significantly inhibited tumor growth compared with control group. The frequencies of CD4+ and CD8+ T cells in spleens of tumor mice and their activation status were significantly increased in HPV-CGN-DC group, but the frequencies of natural regulatory T cells and CD11b+Gr-1+ cells were significantly decreased. Further, HPV-CGN-DC induced strong CD8+ T cell responses, which are negatively correlated with tumor volumes. The results suggested that λ-carrageenan promoted DC maturation through TLR4 signaling pathway and could be used as the adjuvant in DC-based vaccines.

Humoral and cellular immune responses to Yersinia pestis Pla antigen in humans immunized with live plague vaccine.

PubMed

Feodorova, Valentina A; Lyapina, Anna M; Khizhnyakova, Maria A; Zaitsev, Sergey S; Sayapina, Lidiya V; Arseneva, Tatiana E; Trukhachev, Alexey L; Lebedeva, Svetlana A; Telepnev, Maxim V; Ulianova, Onega V; Lyapina, Elena P; Ulyanov, Sergey S; Motin, Vladimir L

2018-06-01

To establish correlates of human immunity to the live plague vaccine (LPV), we analyzed parameters of cellular and antibody response to the plasminogen activator Pla of Y. pestis. This outer membrane protease is an essential virulence factor that is steadily expressed by Y. pestis. PBMCs and sera were obtained from a cohort of naïve (n = 17) and LPV-vaccinated (n = 34) donors. Anti-Pla antibodies of different classes and IgG subclasses were determined by ELISA and immunoblotting. The analysis of antibody response was complicated with a strong reactivity of Pla with normal human sera. The linear Pla B-cell epitopes were mapped using a library of 15-mer overlapping peptides. Twelve peptides that reacted specifically with sera of vaccinated donors were found together with a major cross-reacting peptide IPNISPDSFTVAAST located at the N-terminus. PBMCs were stimulated with recombinant Pla followed by proliferative analysis and cytokine profiling. The T-cell recall response was pronounced in vaccinees less than a year post-immunization, and became Th17-polarized over time after many rounds of vaccination. The Pla protein can serve as a biomarker of successful vaccination with LPV. The diagnostic use of Pla will require elimination of cross-reactive parts of the antigen.

Vaccination of rhesus macaques with the anthrax vaccine adsorbed vaccine produces a serum antibody response that effectively neutralizes receptor-bound protective antigen in vitro.

PubMed

Clement, Kristin H; Rudge, Thomas L; Mayfield, Heather J; Carlton, Lena A; Hester, Arelis; Niemuth, Nancy A; Sabourin, Carol L; Brys, April M; Quinn, Conrad P

2010-11-01

Anthrax toxin (ATx) is composed of the binary exotoxins lethal toxin (LTx) and edema toxin (ETx). They have separate effector proteins (edema factor and lethal factor) but have the same binding protein, protective antigen (PA). PA is the primary immunogen in the current licensed vaccine anthrax vaccine adsorbed (AVA [BioThrax]). AVA confers protective immunity by stimulating production of ATx-neutralizing antibodies, which could block the intoxication process at several steps (binding of PA to the target cell surface, furin cleavage, toxin complex formation, and binding/translocation of ATx into the cell). To evaluate ATx neutralization by anti-AVA antibodies, we developed two low-temperature LTx neutralization activity (TNA) assays that distinguish antibody blocking before and after binding of PA to target cells (noncomplexed [NC] and receptor-bound [RB] TNA assays). These assays were used to investigate anti-PA antibody responses in AVA-vaccinated rhesus macaques (Macaca mulatta) that survived an aerosol challenge with Bacillus anthracis Ames spores. Results showed that macaque anti-AVA sera neutralized LTx in vitro, even when PA was prebound to cells. Neutralization titers in surviving versus nonsurviving animals and between prechallenge and postchallenge activities were highly correlated. These data demonstrate that AVA stimulates a myriad of antibodies that recognize multiple neutralizing epitopes and confirm that change, loss, or occlusion of epitopes after PA is processed from PA83 to PA63 at the cell surface does not significantly affect in vitro neutralizing efficacy. Furthermore, these data support the idea that the full-length PA83 monomer is an appropriate immunogen for inclusion in next-generation anthrax vaccines.

B Lymphocyte Stimulator Levels in Systemic Lupus Erythematosus: Higher Circulating Levels in African American Patients and Increased Production after Influenza Vaccination in Patients with Low Baseline Levels

PubMed Central

Ritterhouse, Lauren L.; Crowe, Sherry R.; Niewold, Timothy B.; Merrill, Joan T.; Roberts, Virginia C.; Dedeke, Amy B.; Neas, Barbara R.; Thompson, Linda F.; Guthridge, Joel M.; James, Judith A.

2011-01-01

Objective Examine the relationship between circulating B lymphocyte stimulator (BLyS) levels and humoral responses to influenza vaccination in systemic lupus erythematosus (SLE) patients, as well as the effect of vaccination on BLyS levels. Clinical and serologic features of SLE that are associated with elevated BLyS levels will also be investigated. Methods Clinical history, disease activity measurements and blood specimens were collected from sixty SLE patients at baseline and after influenza vaccination. Sera were tested for BLyS levels, lupus-associated autoantibodies, serum IFN-α activity, 25-hydroxyvitamin D, and humoral responses to influenza vaccination. Results Thirty percent of SLE patients had elevated BLyS levels, with African American patients having higher BLyS levels than European American patients (p=0.006). Baseline BLyS levels in patients were not correlated with humoral responses to influenza vaccination (p=0.863), and BLyS levels increased post-vaccination only in the subset of patients in the lowest quartile of BLyS levels (p=0.0003). Elevated BLyS levels were associated with increased disease activity as measured by SLEDAI, PGA, and SLAM in European Americans (p=0.035, p=0.016, p=0.018, respectively), but not in African Americans. Elevated BLyS levels were also associated with anti-nRNP (p=0.0003) and decreased 25(OH)D (p=0.018). Serum IFN-α activity was a significant predictor of elevated BLyS in a multivariate analysis (p=0.002). Conclusion African American SLE patients have higher BLyS levels regardless of disease activity. Humoral response to influenza vaccination is not correlated with baseline BLyS levels in SLE patients and only those patients with low baseline BLyS levels demonstrate an increased BLyS response after vaccination. PMID:22127709

Impact of BRICS’ investment in vaccine development on the global vaccine market

PubMed Central

Milstien, Julie; Schmitt, Sarah

2014-01-01

Abstract Brazil, the Russian Federation, India, China and South Africa – the countries known as BRICS – have made considerable progress in vaccine production, regulation and development over the past 20 years. In 1993, all five countries were producing vaccines but the processes used were outdated and non-standardized, there was little relevant research and there was negligible international recognition of the products. By 2014, all five countries had strong initiatives for the development of vaccine technology and had greatly improved their national regulatory capacity. South Africa was then the only BRICS country that was not completely producing vaccines. South Africa is now in the process of re-establishing its own vaccine production and passing beyond the stage of simply importing, formulating and filling vaccine bulks. Changes in the public sector’s price per dose of selected vaccines, the global market share represented by products from specific manufacturers, and the attractiveness, for multinational companies, of partnership and investment opportunities in BRICS companies have all been analysed. The results indicate that the BRICS countries have had a major impact on vaccine price and availability, with much of that impact attributable to the output of Indian vaccine manufacturers. China is expected to have a greater impact soon, given the anticipated development of Chinese vaccine manufacturers in the near future. BRICS’ accomplishments in the field of vaccine development are expected to reshape the global vaccine market and accelerate access to vaccines in the developing world. The challenge is to turn these expectations into strategic actions and practical outcomes. PMID:24940018

Impact of BRICS' investment in vaccine development on the global vaccine market.

PubMed

Kaddar, Miloud; Milstien, Julie; Schmitt, Sarah

2014-06-01

Brazil, the Russian Federation, India, China and South Africa--the countries known as BRICS--have made considerable progress in vaccine production, regulation and development over the past 20 years. In 1993, all five countries were producing vaccines but the processes used were outdated and non-standardized, there was little relevant research and there was negligible international recognition of the products. By 2014, all five countries had strong initiatives for the development of vaccine technology and had greatly improved their national regulatory capacity. South Africa was then the only BRICS country that was not completely producing vaccines. South Africa is now in the process of re-establishing its own vaccine production and passing beyond the stage of simply importing, formulating and filling vaccine bulks. Changes in the public sector's price per dose of selected vaccines, the global market share represented by products from specific manufacturers, and the attractiveness, for multinational companies, of partnership and investment opportunities in BRICS companies have all been analysed. The results indicate that the BRICS countries have had a major impact on vaccine price and availability, with much of that impact attributable to the output of Indian vaccine manufacturers. China is expected to have a greater impact soon, given the anticipated development of Chinese vaccine manufacturers in the near future. BRICS' accomplishments in the field of vaccine development are expected to reshape the global vaccine market and accelerate access to vaccines in the developing world. The challenge is to turn these expectations into strategic actions and practical outcomes.

Intranasal vaccination with an inactivated whole influenza virus vaccine induces strong antibody responses in serum and nasal mucus of healthy adults

PubMed Central

Ainai, Akira; Tamura, Shin-ichi; Suzuki, Tadaki; van Riet, Elly; Ito, Ryo; Odagiri, Takato; Tashiro, Masato; Kurata, Takeshi; Hasegawa, Hideki

2013-01-01

Haemagglutination inhibition (HI) and neutralization (NT) titers as well as haemagglutinin (HA) specific antibody responses were examined in 50 healthy adults aged between 22 and 69 y old after two intranasal administrations of an inactivated whole virus vaccine derived from A/Victoria/210/2009 virus (45 μg HA per dose) at 3 week intervals. Serum HI titers after two-doses of the nasal vaccine showed >2.5-fold rise in the ratio of geometric mean titer upon vaccination, >40% of subjects with a ≥4-fold increase in titer and >70% of subjects with a titer of ≥1:40, all parameters associated with an effective outcome of vaccination in the criteria defined by the European Medicines Agency. Serum neutralizing antibody responses correlated with HI antibody responses, although NT titers were about 2-fold higher than HI titers. These high levels of serum responses were accompanied by high levels of HI and neutralizing antibody responses in nasal mucus as measured in concentrated nasal wash samples that were about 10 times diluted compared with natural nasal mucus. Serum and nasal HI and neutralizing antibody responses consisted of HA-specific IgG and IgA antibody responses, with IgG and IgA antibodies being dominant in serum and nasal responses, respectively. PMID:23896606

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

Beyond empiricism: informing vaccine development through innate immunity research.

PubMed

Levitz, Stuart M; Golenbock, Douglas T

2012-03-16

Although a great public heath success, vaccines provide suboptimal protection in some patient populations and are not available to protect against many infectious diseases. Insights from innate immunity research have led to a better understanding of how existing vaccines work and have informed vaccine development. New adjuvants and delivery systems are being designed based upon their capacity to stimulate innate immune sensors and target antigens to dendritic cells, the cells responsible for initiating adaptive immune responses. Incorporating these adjuvants and delivery systems in vaccines can beneficially alter the quantitative and qualitative nature of the adaptive immune response, resulting in enhanced protection. Copyright © 2012 Elsevier Inc. All rights reserved.

A Review of Clinical Trials of Human Papillomavirus Prophylactic Vaccines

PubMed Central

Schiller, John T.; Castellsagué, Xavier; Garland, Suzanne M.

2015-01-01

End of study analyses of the phase III trials of prophylactic human papillomavirus (HPV) virus-like particle (VLP) vaccines in young women are now largely completed. Two distinct vaccines were evaluated, Gardasil® (Merck & Co., Whitehouse Station, NJ USA) a quadrivalent vaccine containing VLPs of types 6, 11, 16 and 18 and Cervarix® (GlaxoSmithKline Biologicals, Rixensart, Belgium), a bivalent vaccine containing VLPs of types 16 and 18. Both vaccines exhibited excellent safety and immunogenicity profiles. The vaccines also demonstrated remarkably high and similar efficacy against the vaccine-targeted types for a range of cervical endpoints from persistent infection to cervical intraepithelial neoplasia grade 3 (CIN3) in women naïve to the corresponding type at the time of vaccination. However, protection from incident infection or disease from non-vaccine types was restricted, and the vaccines had no effect on prevalent infection or disease. Gardasil® also demonstrated strong protection against genital warts and vulvar/vaginal neoplasia associated with the vaccine types. In other trials, Gardasil® protected mid-adult women from incident infection and CIN caused by the vaccine types and protected men for incident infection, genital warts and anal intraepithelial neoplasia by the vaccine types. Cervarix® protected against vaccine-targeted anal infections in women in an end of study evaluation. For practical reasons, efficacy studies have not been conducted in the primary target populations of current vaccination programs, adolescent girls and boys. However, immunogenicity bridging studies demonstrating excellent safety and strong immune responses in adolescence, coupled with the documentation of durable antibody responses and protection in young adults, leads to an optimistic projection of the effectiveness of the vaccines in adolescent vaccination programs. Taken together, the excellent clinical trial results strongly support the potential of the vaccines as

Vaccines and the infant's immune system--what nurses need to know.

PubMed

Heurter, Helen; Langman, Eileen

2005-01-01

Vaccines prevent serious infections by stimulating the immune system to identify and destroy invading organisms rapidly before they have a chance to cause disease. Armed with the scientific facts to refute current misconceptions surrounding vaccines and the infant's immune system, nurses can provide parents with the answers they need.

Vaccine Hesitancy Among Caregivers and Association with Childhood Vaccination Timeliness in Addis Ababa, Ethiopia.

PubMed

Masters, Nina B; Tefera, Yemesrach A; Wagner, Abram L; Boulton, Matthew L

2018-05-24

Vaccines are vital to reducing childhood mortality, and prevent an estimated 2 to 3 million deaths annually which disproportionately occur in the developing world. Overall vaccine coverage is typically used as a metric to evaluate the adequacy of vaccine program performance, though it does not account for untimely administration, which may unnecessarily prolong children's susceptibility to disease. This study explored a hypothesized positive association between increasing vaccine hesitancy and untimeliness of immunizations administered under the Expanded Program on Immunization (EPI) in Addis Ababa, Ethiopia. This cross-sectional survey employed a multistage sampling design, randomly selecting one health center within five sub-cities of Addis Ababa. Caregivers of 3 to 12-month-old infants completed a questionnaire on vaccine hesitancy, and their infants' vaccination cards were examined to assess timeliness of received vaccinations. The sample comprised 350 caregivers. Overall, 82.3% of the surveyed children received all recommended vaccines, although only 55.9% of these vaccinations were timely. Few caregivers (3.4%) reported ever hesitating and 3.7% reported ever refusing a vaccine for their child. Vaccine hesitancy significantly increased the odds of untimely vaccination (AOR 1.94, 95% CI: 1.02, 3.71) in the adjusted analysis. This study found high vaccine coverage among a sample of 350 young children in Addis Ababa, though only half received all recommended vaccines on time. High vaccine hesitancy was strongly associated with infants' untimely vaccination, indicating that increased efforts to educate community members and providers about vaccines may have a beneficial impact on vaccine timeliness in Addis Ababa.

Development of Membrane-Bound GM-CSF and IL-18 as an Effective Tumor Vaccine

PubMed Central

Cheng, Ta-Chun; Chuang, Chih-Hung; Kao, Chien-Han; Hsieh, Yuan-Chin; Cheng, Kuang-Hung; Wang, Jaw-Yuan; Cheng, Chiu-Min; Chen, Chien-Shu; Cheng, Tian-Lu

2015-01-01

The development of effective adjuvant is the key factor to boost the immunogenicity of tumor cells as a tumor vaccine. In this study, we expressed membrane-bound granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-18 (IL-18) as adjuvants in tumor cells to stimulate immune response. B7 transmembrane domain fused GM-CSF and IL-18 was successfully expressed in the cell membrane and stimulated mouse splenocyte proliferation. Co-expression of GM-CSF and IL-18 reduced tumorigenesis (P<0.05) and enhanced tumor protective efficacy (P<0.05) significantly in comparison with GM-CSF alone. These results indicated that the combination of GM-CSF andIL-18 will enhance the immunogenicity of a cell-based anti-tumor vaccine. This membrane-bound approach can be applied to other cytokines for the development of novel vaccine strategies. PMID:26186692

Universal influenza vaccines: Shifting to better vaccines.

PubMed

Berlanda Scorza, Francesco; Tsvetnitsky, Vadim; Donnelly, John J

2016-06-03

Influenza virus causes acute upper and lower respiratory infections and is the most likely, among known pathogens, to cause a large epidemic in humans. Influenza virus mutates rapidly, enabling it to evade natural and vaccine-induced immunity. Furthermore, influenza viruses can cross from animals to humans, generating novel, potentially pandemic strains. Currently available influenza vaccines induce a strain specific response and may be ineffective against new influenza viruses. The difficulty in predicting circulating strains has frequently resulted in mismatch between the annual vaccine and circulating viruses. Low-resource countries remain mostly unprotected against seasonal influenza and are particularly vulnerable to future pandemics, in part, because investments in vaccine manufacturing and stockpiling are concentrated in high-resource countries. Antibodies that target conserved sites in the hemagglutinin stalk have been isolated from humans and shown to confer protection in animal models, suggesting that broadly protective immunity may be possible. Several innovative influenza vaccine candidates are currently in preclinical or early clinical development. New technologies include adjuvants, synthetic peptides, virus-like particles (VLPs), DNA vectors, messenger RNA, viral vectors, and attenuated or inactivated influenza viruses. Other approaches target the conserved exposed epitope of the surface exposed membrane matrix protein M2e. Well-conserved influenza proteins, such as nucleoprotein and matrix protein, are mainly targeted for developing strong cross-protective T cell responses. With multiple vaccine candidates moving along the testing and development pipeline, the field is steadily moving toward a product that is more potent, durable, and broadly protective than previously licensed vaccines. Copyright © 2016 World Health Organization. Published by Elsevier Ltd.. All rights reserved.

DNA Vaccination Against Metastatic Breast Cancer

DTIC Science & Technology

2002-07-01

Although DNA vaccines have shown effectiveness in clinical trials , it is essential to demonstrate pre- clinical effectiveness for anti-tumor DNA vaccines...been shown to induce strong anti-tumor immunity in mice (3). Although gene vaccines have shown effectiveness in clinical trials for infectious...stronger justification for a clinical trial . REFERENCES: 1. Fornier, M., P. Munster, and A. D. Seidman. 1999. Update on the management of advanced breast

Newcastle Disease Virus as a Vaccine Vector for Development of Human and Veterinary Vaccines

PubMed Central

Kim, Shin-Hee; Samal, Siba K.

2016-01-01

Viral vaccine vectors have shown to be effective in inducing a robust immune response against the vaccine antigen. Newcastle disease virus (NDV), an avian paramyxovirus, is a promising vaccine vector against human and veterinary pathogens. Avirulent NDV strains LaSota and B1 have long track records of safety and efficacy. Therefore, use of these strains as vaccine vectors is highly safe in avian and non-avian species. NDV replicates efficiently in the respiratory track of the host and induces strong local and systemic immune responses against the foreign antigen. As a vaccine vector, NDV can accommodate foreign sequences with a good degree of stability and as a RNA virus, there is limited possibility for recombination with host cell DNA. Using NDV as a vaccine vector in humans offers several advantages over other viral vaccine vectors. NDV is safe in humans due to host range restriction and there is no pre-existing antibody to NDV in the human population. NDV is antigenically distinct from common human pathogens. NDV replicates to high titer in a cell line acceptable for human vaccine development. Therefore, NDV is an attractive vaccine vector for human pathogens for which vaccines are currently not available. NDV is also an attractive vaccine vector for animal pathogens. PMID:27384578

Newcastle Disease Virus as a Vaccine Vector for Development of Human and Veterinary Vaccines.

PubMed

Kim, Shin-Hee; Samal, Siba K

2016-07-04

Viral vaccine vectors have shown to be effective in inducing a robust immune response against the vaccine antigen. Newcastle disease virus (NDV), an avian paramyxovirus, is a promising vaccine vector against human and veterinary pathogens. Avirulent NDV strains LaSota and B1 have long track records of safety and efficacy. Therefore, use of these strains as vaccine vectors is highly safe in avian and non-avian species. NDV replicates efficiently in the respiratory track of the host and induces strong local and systemic immune responses against the foreign antigen. As a vaccine vector, NDV can accommodate foreign sequences with a good degree of stability and as a RNA virus, there is limited possibility for recombination with host cell DNA. Using NDV as a vaccine vector in humans offers several advantages over other viral vaccine vectors. NDV is safe in humans due to host range restriction and there is no pre-existing antibody to NDV in the human population. NDV is antigenically distinct from common human pathogens. NDV replicates to high titer in a cell line acceptable for human vaccine development. Therefore, NDV is an attractive vaccine vector for human pathogens for which vaccines are currently not available. NDV is also an attractive vaccine vector for animal pathogens.

Epitope-based recombinant diagnostic antigen to distinguish natural infection from vaccination with hepatitis A virus vaccines.

PubMed

Su, Qiudong; Guo, Minzhuo; Jia, Zhiyuan; Qiu, Feng; Lu, Xuexin; Gao, Yan; Meng, Qingling; Tian, Ruiguang; Bi, Shengli; Yi, Yao

2016-07-01

Hepatitis A virus (HAV) infection can stimulate the production of antibodies to structural and non-structural proteins of the virus. However, vaccination with an inactivated or attenuated HAV vaccine produces antibodies mainly against structural proteins, whereas no or very limited antibodies are produced against the non-structural proteins. Current diagnostic assays to determine exposure to HAV, such as the Abbott HAV AB test, detect antibodies only to the structural proteins and so are not able to distinguish a natural infection from vaccination with an inactivated or attenuated virus. Here, we constructed a recombinant tandem multi-epitope diagnostic antigen (designated 'H1') based on the immune-dominant epitopes of the non-structural proteins of HAV to distinguish the two situations. H1 protein expressed in Escherichia coli and purified by affinity and anion exchange chromatography was applied in a double-antigen sandwich ELISA for the detection of anti-non-structural HAV proteins, which was confirmed to distinguish a natural infection from vaccination with an inactivated or attenuated HAV vaccine. Copyright © 2016 Elsevier B.V. All rights reserved.

Genome-Wide Characterization of Transcriptional Patterns in High and Low Antibody Responders to Rubella Vaccination

PubMed Central

Haralambieva, Iana H.; Oberg, Ann L.; Ovsyannikova, Inna G.; Kennedy, Richard B.; Grill, Diane E.; Middha, Sumit; Bot, Brian M.; Wang, Vivian W.; Smith, David I.; Jacobson, Robert M.; Poland, Gregory A.

2013-01-01

Immune responses to current rubella vaccines demonstrate significant inter-individual variability. We performed mRNA-Seq profiling on PBMCs from high and low antibody responders to rubella vaccination to delineate transcriptional differences upon viral stimulation. Generalized linear models were used to assess the per gene fold change (FC) for stimulated versus unstimulated samples or the interaction between outcome and stimulation. Model results were evaluated by both FC and p-value. Pathway analysis and self-contained gene set tests were performed for assessment of gene group effects. Of 17,566 detected genes, we identified 1,080 highly significant differentially expressed genes upon viral stimulation (p<1.00E−15, FDR<1.00E−14), including various immune function and inflammation-related genes, genes involved in cell signaling, cell regulation and transcription, and genes with unknown function. Analysis by immune outcome and stimulation status identified 27 genes (p≤0.0006 and FDR≤0.30) that responded differently to viral stimulation in high vs. low antibody responders, including major histocompatibility complex (MHC) class I genes (HLA-A, HLA-B and B2M with p = 0.0001, p = 0.0005 and p = 0.0002, respectively), and two genes related to innate immunity and inflammation (EMR3 and MEFV with p = 1.46E−08 and p = 0.0004, respectively). Pathway and gene set analysis also revealed transcriptional differences in antigen presentation and innate/inflammatory gene sets and pathways between high and low responders. Using mRNA-Seq genome-wide transcriptional profiling, we identified antigen presentation and innate/inflammatory genes that may assist in explaining rubella vaccine-induced immune response variations. Such information may provide new scientific insights into vaccine-induced immunity useful in rational vaccine development and immune response monitoring. PMID:23658707

Three-year duration of immunity in cats vaccinated with a canarypox-vectored recombinant rabies virus vaccine.

PubMed

Jas, D; Coupier, C; Toulemonde, C Edlund; Guigal, P-M; Poulet, H

2012-11-19

Despite the availability of efficacious vaccines for animals and humans, rabies is still a major zoonosis. Prevention of rabies in dogs and cats is key for reducing the risk of transmission of this deadly disease to humans. Most veterinary vaccines are adjuvanted inactivated vaccines and have been shown to provide one to four-year duration of immunity. In response to debates about the safety of adjuvanted vaccines in cats, a non-adjuvanted feline rabies vaccine with one-year duration of immunity claim was specifically developed using the canarypoxvirus vector technology. The objective of this study was to validate a vaccination program based on primary vaccination, revaccination one year later and boosters every three years. Seronegative cats were vaccinated at 12 weeks of age and received a booster vaccination one year later. This vaccination regimen induced a strong and sustained antibody response, and all vaccinated animals were protected against virulent rabies challenge carried out 3 years after vaccination. These results validated 3-year duration of immunity after a complete basic vaccination program consisting in primary vaccination from 12 weeks of age followed by revaccination one year later with a non-adjuvanted canarypox-vectored vaccine. Copyright © 2012 Elsevier Ltd. All rights reserved.

Innovation Partnership for a Roadmap on Vaccines in Europe (IPROVE): A vision for the vaccines of tomorrow.

PubMed

Medaglini, Donata; De Azero, Magdalena R; Leroy, Odile; Bietrix, Florence; Denoel, Philippe

2018-02-21

A clear vision for vaccines research and development (R&D) is needed if Europe is to continue to lead the discovery of next generation vaccines. Innovation Partnership for a Roadmap on Vaccines in Europe (IPROVE) is a collaboration between leading vaccine experts to develop a roadmap setting out how Europe can best invest in the science and technology essential for vaccines innovation. This FP7 project, started in December 2013, brought together more than 130 key public and private stakeholders from academia, public health institutes, regulators, industry and small and medium-sized enterprises to determine and prioritise the gaps and challenges to be addressed to bolster innovation in vaccines and vaccination in Europe. The IPROVE consultation process was structured around seven themes: vaccine R&D, manufacturing and quality control, infrastructure, therapeutic vaccines, needs of small and medium-sized enterprises, vaccines acceptance and training needs. More than 80 recommendations were made by the consultation groups, mainly focused on the need for a multidisciplinary research approach to stimulate innovation, accelerated translation of scientific knowledge into technological innovation, and fostering of real collaboration within the European vaccine ecosystem. The consultation also reinforced the fact that vaccines are only as good as their vaccine implementation programmes, and that more must be done to understand and address vaccination hesitancy of both the general public and healthcare professionals. Bringing together a wide range of stakeholders to work on the IPROVE roadmap has increased mutual understanding of their different perspectives, needs and priorities. IPROVE is a first attempt to develop such a comprehensive view of the vaccine sector. This prioritisation effort, aims to help policy-makers and funders identify those vaccine-related areas and technologies where key investment is needed for short and medium-long term success. Copyright © 2017 The

Vaccine and microbicide tax credit legislation introduced in Congress.

PubMed

1999-04-02

The Lifesaving Vaccine Technology Act of 1999, a House bill to stimulate HIV vaccine research and development, has been introduced by Representative Nancy Pelosi (D - Calif.), Representative Charles Rangel (D - N.Y.), and seven other cosponsors. Pelosi presents a summary of the Act, which may offer tax credits to companies for vaccine research costs in the areas of malaria, tuberculosis, HIV, or other infectious diseases. These companies would also be obligated to establish a way of maximizing access to the vaccine. The Act reflects the idea that the President and specific Federal agencies should work together to increase vaccine access. The need for this Act is shown in the 1998 survey results from Pharmaceutical Research and Manufacturers of America, which indicate that none of the 43 vaccines in development were for HIV. Information is provided for accessing the full-text of the Act.

Comparison of Th1- and Th2-associated immune reactivities stimulated by single versus multiple vaccination of mice with irradiated Schistosoma mansoni cercariae

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

Caulada-Benedetti, Z.; Al-Zamel, F.; Sher, A.

1991-03-01

Mice immunized against Schistosoma mansoni by a single percutaneous exposure to radiation-attenuated parasite larvae demonstrate partial resistance to challenge infection that has been shown to correlate with development of cell-mediated immunity, whereas mice hyperimmunized by multiple exposure to attenuated larvae produce antibodies capable of transferring partial protection to naive recipients. Measurement of Ag-specific lymphokine responses in these animals suggested that the difference in resistance mechanisms may be due to the differential induction of Th subset response by the two immunization protocols. Thus, upon Ag stimulation, singly immunized mice predominantly demonstrated responses associated with Th1 reactivity, including IL-2 and IFN-gamma production,more » whereas multiply immunized animals showed increased IL-5, IL-4, and IgG1 antibody production associated with enhanced Th2 response. These responses demonstrated some degree of organ compartmentalization, with splenocytes demonstrating higher Th1-related lymphokine production and cells from draining lymph nodes showing stronger proliferation and Th2 type reactivity. However, hyperimmunized mice also continued to demonstrate substantial Th1-associated immune reactivity. Moreover, in vivo Ag challenge elicited activated larvacidal macrophages in hyperimmunized animals. These observations indicate that protective cell-mediated mechanisms associated with induction of CD4+ Th1 cell reactivity predominate in singly vaccinated mice. Further vaccination stimulates Th2 responses, such as enhanced IgG1 production, that may also contribute to protective immunity.« less

Yellow fever vaccine YF-17D activates multiple dendritic cell subsets via TLR2, 7, 8, and 9 to stimulate polyvalent immunity.

PubMed

Querec, Troy; Bennouna, Soumaya; Alkan, Sefik; Laouar, Yasmina; Gorden, Keith; Flavell, Richard; Akira, Shizuo; Ahmed, Rafi; Pulendran, Bali

2006-02-20

The live attenuated yellow fever vaccine 17D (YF-17D) is one of the most effective vaccines available, with a 65-yr history of use in >400 million people globally. Despite this efficacy, there is presently no information about the immunological mechanisms by which YF-17D acts. Here, we present data that suggest that YF-17D activates multiple Toll-like receptors (TLRs) on dendritic cells (DCs) to elicit a broad spectrum of innate and adaptive immune responses. Specifically, YF-17D activates multiple DC subsets via TLRs 2, 7, 8, and 9 to elicit the proinflammatory cytokines interleukin (IL)-12p40, IL-6, and interferon-alpha. Interestingly, the resulting adaptive immune responses are characterized by a mixed T helper cell (Th)1/Th2 cytokine profile and antigen-specific CD8+ T cells. Furthermore, distinct TLRs appear to differentially control the Th1/Th2 balance; thus, whilst MyD88-deficient mice show a profound impairment of Th1 cytokines, TLR2-deficient mice show greatly enhanced Th1 and Tc1 responses to YF-17D. Together, these data enhance our understanding of the molecular mechanism of action of YF-17D, and highlight the potential of vaccination strategies that use combinations of different TLR ligands to stimulate polyvalent immune responses.

Lentiviral Protein Transfer Vectors Are an Efficient Vaccine Platform and Induce a Strong Antigen-Specific Cytotoxic T Cell Response

PubMed Central

Uhlig, Katharina M.; Schülke, Stefan; Scheuplein, Vivian A. M.; Malczyk, Anna H.; Reusch, Johannes; Kugelmann, Stefanie; Muth, Anke; Koch, Vivian; Hutzler, Stefan; Bodmer, Bianca S.; Schambach, Axel; Buchholz, Christian J.; Waibler, Zoe; Scheurer, Stephan

2015-01-01

ABSTRACT To induce and trigger innate and adaptive immune responses, antigen-presenting cells (APCs) take up and process antigens. Retroviral particles are capable of transferring not only genetic information but also foreign cargo proteins when they are genetically fused to viral structural proteins. Here, we demonstrate the capacity of lentiviral protein transfer vectors (PTVs) for targeted antigen transfer directly into APCs and thereby induction of cytotoxic T cell responses. Targeting of lentiviral PTVs to APCs can be achieved analogously to gene transfer vectors by pseudotyping the particles with truncated wild-type measles virus (MV) glycoproteins (GPs), which use human SLAM (signaling lymphocyte activation molecule) as a main entry receptor. SLAM is expressed on stimulated lymphocytes and APCs, including dendritic cells. SLAM-targeted PTVs transferred the reporter protein green fluorescent protein (GFP) or Cre recombinase with strict receptor specificity into SLAM-expressing CHO and B cell lines, in contrast to broadly transducing vesicular stomatitis virus G protein (VSV-G) pseudotyped PTVs. Primary myeloid dendritic cells (mDCs) incubated with targeted or nontargeted ovalbumin (Ova)-transferring PTVs stimulated Ova-specific T lymphocytes, especially CD8+ T cells. Administration of Ova-PTVs into SLAM-transgenic and control mice confirmed the observed predominant induction of antigen-specific CD8+ T cells and demonstrated the capacity of protein transfer vectors as suitable vaccines for the induction of antigen-specific immune responses. IMPORTANCE This study demonstrates the specificity and efficacy of antigen transfer by SLAM-targeted and nontargeted lentiviral protein transfer vectors into antigen-presenting cells to trigger antigen-specific immune responses in vitro and in vivo. The observed predominant activation of antigen-specific CD8+ T cells indicates the suitability of SLAM-targeted and also nontargeted PTVs as a vaccine for the induction of

Current state and challenges in developing oral vaccines.

PubMed

Vela Ramirez, Julia E; Sharpe, Lindsey A; Peppas, Nicholas A

2017-05-15

While vaccination remains the most cost effective strategy for disease prevention, communicable diseases persist as the second leading cause of death worldwide. There is a need to design safe, novel vaccine delivery methods to protect against unaddressed and emerging diseases. Development of vaccines administered orally is preferable to traditional injection-based formulations for numerous reasons including improved safety and compliance, and easier manufacturing and administration. Additionally, the oral route enables stimulation of humoral and cellular immune responses at both systemic and mucosal sites to establish broader and long-lasting protection. However, oral delivery is challenging, requiring formulations to overcome the harsh gastrointestinal (GI) environment and avoid tolerance induction to achieve effective protection. Here we address the rationale for oral vaccines, including key biological and physicochemical considerations for next-generation oral vaccine design. Copyright © 2017 Elsevier B.V. All rights reserved.

[The experimental evaluation with flow cytofluorimetry technique of the level of cellular immunologic memory in persons vaccinated against plague and anthrax].

PubMed

Bogacheva, N V; Kriuchkov, A V; Darmov, I V; Vorob'ev, K A; Pechenkin, D V; Elagin, G D; Kolesnikiov, D P

2013-11-01

The article deals with experimental evaluation with flow cytofluorimetry technique of the level of cellular immunologic memory in persons vaccinated with plague and anthrax live dry vaccines. It is established that the introduction of plague and anthrax live dry vaccines into organism of vaccinated persons ignites immunologic rearrangement manifested by reliable increase of level of blood concentration of Th1-lymphocytes (immunologic memory cells) against the background of vaccination. The higher correlation coefficient is detected between leucocytes lysis coefficient and stimulation coefficient according blood concentration level of T-lymphocytes predominantly at the expense of Th1-lymphocytes. The values of stimulation coefficient were calculated for corresponding blood cells of vaccinated persons. This data testifies the effectiveness of application of vaccination against plague and anthrax.

VIOLIN: vaccine investigation and online information network.

PubMed

Xiang, Zuoshuang; Todd, Thomas; Ku, Kim P; Kovacic, Bethany L; Larson, Charles B; Chen, Fang; Hodges, Andrew P; Tian, Yuying; Olenzek, Elizabeth A; Zhao, Boyang; Colby, Lesley A; Rush, Howard G; Gilsdorf, Janet R; Jourdian, George W; He, Yongqun

2008-01-01

Vaccines are among the most efficacious and cost-effective tools for reducing morbidity and mortality caused by infectious diseases. The vaccine investigation and online information network (VIOLIN) is a web-based central resource, allowing easy curation, comparison and analysis of vaccine-related research data across various human pathogens (e.g. Haemophilus influenzae, human immunodeficiency virus (HIV) and Plasmodium falciparum) of medical importance and across humans, other natural hosts and laboratory animals. Vaccine-related peer-reviewed literature data have been downloaded into the database from PubMed and are searchable through various literature search programs. Vaccine data are also annotated, edited and submitted to the database through a web-based interactive system that integrates efficient computational literature mining and accurate manual curation. Curated information includes general microbial pathogenesis and host protective immunity, vaccine preparation and characteristics, stimulated host responses after vaccination and protection efficacy after challenge. Vaccine-related pathogen and host genes are also annotated and available for searching through customized BLAST programs. All VIOLIN data are available for download in an eXtensible Markup Language (XML)-based data exchange format. VIOLIN is expected to become a centralized source of vaccine information and to provide investigators in basic and clinical sciences with curated data and bioinformatics tools for vaccine research and development. VIOLIN is publicly available at http://www.violinet.org.

Varicella-zoster virus vaccine, successes and difficulties.

PubMed

Sarkadi, Julia

2013-12-01

Despite intensive efforts in recent decades to develop preventive or therapeutic vaccines against diseases caused by herpes simplex virus (HSV), or varicella-zoster virus (VZV), members of the Alpha herpes virinae subfamily of human herpes viruses,a safe and efficient vaccine has been approved for commercial development only against VZV. The VZV vaccine contains a live attenuated strain, OKA. It consists of amixture of at least 13 subpopulations of viruses, all with deletions, insertions or mutations in the genome; the most common mutations are observed in the open reading frame 62 (ORF62). Experience over more than 30 years in Japan, the USA and other countries where VZV vaccination is provided has demonstrated that the vaccine is safe and the effectiveness of two doses compared to unvaccinated children is 98-99%. When administered in a higher dose to stimulate the declining cell-mediated immunity, the same vaccine has been shown to reduce the incidence and severity of herpes zoster in immunocompetent individuals older than 60 years. Vaccination of immuno-compromised subjects with this VZV vaccine is problematic and various strategies need to be explored. Differences in the pathomechanisms of infection, latency and immune evasion of VZV and HSV, together with host genetic factors, may explain the availability of the successful VZV vaccine and the failures of the past HSV vaccine candidates.

Cellular Immune Responses to Nine Mycobacterium tuberculosis Vaccine Candidates following Intranasal Vaccination

PubMed Central

Sable, Suraj B.; Cheruvu, Mani; Nandakumar, Subhadra; Sharma, Sunita; Bandyopadhyay, Kakali; Kellar, Kathryn L.; Posey, James E.; Plikaytis, Bonnie B.; Amara, Rama Rao; Shinnick, Thomas M.

2011-01-01

Background The identification of Mycobacterium tuberculosis vaccines that elicit a protective immune response in the lungs is important for the development of an effective vaccine against tuberculosis. Methods and Principal Findings In this study, a comparison of intranasal (i.n.) and subcutaneous (s.c.) vaccination with the BCG vaccine demonstrated that a single moderate dose delivered intranasally induced a stronger and sustained M. tuberculosis-specific T-cell response in lung parenchyma and cervical lymph nodes of BALB/c mice than vaccine delivered subcutaneously. Both BCG and a multicomponent subunit vaccine composed of nine M. tuberculosis recombinant proteins induced strong antigen-specific T-cell responses in various local and peripheral immune compartments. Among the nine recombinant proteins evaluated, the alanine proline rich antigen (Apa, Rv1860) was highly antigenic following i.n. BCG and immunogenic after vaccination with a combination of the nine recombinant antigens. The Apa-induced responses included induction of both type 1 and type 2 cytokines in the lungs as evaluated by ELISPOT and a multiplexed microsphere-based cytokine immunoassay. Of importance, i.n. subunit vaccination with Apa imparted significant protection in the lungs and spleen of mice against M. tuberculosis challenge. Despite observed differences in the frequencies and location of specific cytokine secreting T cells both BCG vaccination routes afforded comparable levels of protection in our study. Conclusion and Significance Overall, our findings support consideration and further evaluation of an intranasally targeted Apa-based vaccine to prevent tuberculosis. PMID:21799939

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.

Understanding modern-day vaccines: what you need to know.

PubMed

Vetter, Volker; Denizer, Gülhan; Friedland, Leonard R; Krishnan, Jyothsna; Shapiro, Marla

2018-03-01

Vaccines are considered to be one of the greatest public health achievements of the last century. Depending on the biology of the infection, the disease to be prevented, and the targeted population, a vaccine may require the induction of different adaptive immune mechanisms to be effective. Understanding the basic concepts of different vaccines is therefore crucial to understand their mode of action, benefits, risks, and their potential real-life impact on protection. This review aims to provide healthcare professionals with background information about the main vaccine designs and concepts of protection in a simplified way to improve their knowledge and understanding, and increase their confidence in the science of vaccination ( Supplementary Material ). KEY MESSAGE Different vaccine designs, each with different advantages and limitations, can be applied for protection against a particular disease. Vaccines may contain live-attenuated pathogens, inactivated pathogens, or only parts of pathogens and may also contain adjuvants to stimulate the immune responses. This review explains the mode of action, benefits, risks and real-life impact of vaccines by highlighting key vaccine concepts. An improved knowledge and understanding of the main vaccine designs and concepts of protection will help support the appropriate use and expectations of vaccines, increase confidence in the science of vaccination, and help reduce vaccine hesitancy.

Cell-mediated and humoral immune responses induced by scarification vaccination of human volunteers with a new lot of the live vaccine strain of Francisella tularensis.

PubMed Central

Waag, D M; Galloway, A; Sandstrom, G; Bolt, C R; England, M J; Nelson, G O; Williams, J C

1992-01-01

Tularemia is a disease caused by the facultative intracellular bacterium Francisella tularensis. We evaluated a new lot of live F. tularensis vaccine for its immunogenicity in human volunteers. Scarification vaccination induced humoral and cell-mediated immune responses. Indications of a positive immune response after vaccination included an increase in specific antibody levels, which were measured by enzyme-linked immunosorbent and immunoblot assays, and the ability of peripheral blood lymphocytes to respond to whole F. tularensis bacteria as recall antigens. Vaccination caused a significant rise (P less than 0.05) in immunoglobulin A (IgA), IgG, and IgM titers. Lymphocyte stimulation indices were significantly increased (P less than 0.01) in vaccinees 14 days after vaccination. These data verify that this new lot of live F. tularensis vaccine is immunogenic. Images PMID:1400988

The future for blood-stage vaccines against malaria.

PubMed

Richards, Jack S; Beeson, James G

2009-07-01

Malaria is a leading cause of mortality and morbidity globally, and effective vaccines are urgently needed. Malaria vaccine approaches can be broadly grouped as pre-erythrocytic, blood stage and transmission blocking. This review focuses on blood-stage vaccines, and considers the evidence supporting the development of blood-stage vaccines, the advantages and challenges of this approach, potential targets, human vaccine studies and future directions. There is a strong rationale for the development of vaccines based on antigens of blood-stage parasites. Symptomatic malaria is caused by blood-stage parasitemia and acquired immunity in humans largely targets blood-stage antigens. Several candidate vaccines have proved efficacious in animal models and at least one vaccine showed partial efficacy in a clinical trial. At present, all leading candidate blood-stage antigens are merozoite proteins, located on the merozoite surface or within the apical organelles. Major challenges and priorities include overcoming antigenic diversity, identification of protective epitopes, understanding the nature and targets of protective immune responses, and defining antigen combinations that give the greatest efficacy. Additionally, objective criteria and approaches are needed to prioritize the large number of candidate antigens, and strong candidates need to be tested in clinical trials as quickly as possible.

HSV-2: in pursuit of a vaccine

PubMed Central

Johnston, Christine; Koelle, David M.; Wald, Anna

2011-01-01

Herpes simplex virus type 2 (HSV-2) is one of the most prevalent sexually transmitted infections worldwide. In addition to recurrent genital ulcers, HSV-2 causes neonatal herpes, and it is associated with a 3-fold increased risk for HIV acquisition. Although many HSV-2 vaccines have been studied in animal models, few have reached clinical trials, and those that have been tested in humans were not consistently effective. Here, we review HSV-2 pathogenesis, with a focus on novel understanding of mucosal immunobiology of HSV-2, and vaccine efforts to date, in an attempt to stimulate thinking about future directions for development of effective prophylactic and therapeutic HSV-2 vaccines. PMID:22133885

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

Status of arenavirus vaccines and their application

PubMed Central

Johnson, Karl M.

1975-01-01

A limited but definite need exists for vaccines against Lassa, Junin, and Machupo viruses. Medical and laboratory personnel, as well as defined high-risk population groups, require protection from these highly virulent agents. To date little work has been done on inactivated vaccines for these viruses. A live attenuated Junin vaccine has been tested successfully in more than 600 persons, and a high-passage Machupo virus strain has protected rhesus monkeys against lethal infection produced by a homologous field strain. Work has been initiated on possible heterologous protection induced by infection or antigenic stimulation with arenaviruses not pathogenic for man. Crucial for the eventual development of effective vaccines are the construction of more maximum security laboratories and the further elucidation of the experimental and natural biology of the agents in lower animals and man. PMID:182407

Milestones in contraceptive vaccines development and hurdles in their application

PubMed Central

Gupta, Satish Kumar; Shrestha, Abhinav; Minhas, Vidisha

2014-01-01

Contraceptive vaccines have been proposed for controlling the growing human population and wildlife population management. Multiple targets such as gonadotropin releasing hormone (GnRH), luteinizing hormone, follicle stimulating hormone, gonadotropin receptors, sperm-specific proteins and zona pellucida glycoproteins have been exploited to develop contraceptive vaccine and their efficacy investigated and shown in various experimental animal models. Vaccines based on GnRH have found application in immuno-castration of male pigs for prevention of boar-taint. Vaccines based on zona pellucida glycoproteins have shown promising results for population management of wild horses and white-tailed deer. Phase II clinical trials in women with β-human chorionic gonadotropin (β-hCG)-based contraceptive vaccine established proof of principle that these can be developed for human application. Block in fertility by β-hCG contraceptive vaccine was reversible. Further research inputs are required to establish the safety of contraceptive vaccines, improve their immunogenicity and to develop novel vaccine delivery platforms for providing long lasting immunity. PMID:24262991

Lack of broad functional differences in immunity in fully vaccinated vs. unvaccinated children.

PubMed

Sherrid, Ashley M; Ruck, Candice E; Sutherland, Darren; Cai, Bing; Kollmann, Tobias R

2017-04-01

Concerns have been raised that with an increase in the number of vaccines administered early in life, immune development could be altered, leading to either increased or decreased immune reactivity. We investigated the impact of vaccination on immune status, contrasting the immune response to general, nonantigen-specific stimuli in a cohort of entirely unvaccinated vs. fully vaccinated children at 3-5 y of age. Innate immunity was assessed by quantifying bulk and cell-type-specific cytokine production in response to stimulation with pathogen associated microbial patterns. Adaptive immune status was characterized by assessing lymphocyte proliferation and cytokine production in response to generic T cell stimuli. Our investigations failed to reveal a broadly evident alteration of either innate or adaptive immunity in vaccinated children. Equivalently robust innate and adaptive responses to pathogen associated microbial patterns and generic T cell stimulants were observed in both groups. Although our sample size was small, our data suggest that standard childhood vaccinations do not lead to long-lasting gross alterations of the immune system.

Engineering intranasal mRNA vaccines to enhance lymph node trafficking and immune responses.

PubMed

Li, Man; Li, You; Peng, Ke; Wang, Ying; Gong, Tao; Zhang, Zhirong; He, Qin; Sun, Xun

2017-12-01

Intranasal mRNA vaccination provides immediate immune protection against pandemic diseases. Recent studies have shown that diverse forms of polyethyleneimine (PEI) have potent mucosal adjuvant activity, which could significantly facilitate the delivery of intranasal mRNA vaccines. Nevertheless, optimizing the chemical structure of PEI to maximize its adjuvanticity and decrease its toxicity remains a challenge. Here we show that the chemical structure of PEI strongly influences how well nanocomplexes of PEI and mRNA migrate to the lymph nodes and elicit immune responses. Conjugating cyclodextrin (CD) with PEI600 or PEI2k yielded CP (CD-PEI) polymers with different CD/PEI ratios. We analyzed the delivery efficacy of CP600, CP2k, and PEI25k as intranasal mRNA vaccine carriers by evaluating the lymph nodes migration and immune responses. Among these polymers, CP2k/mRNA showed significantly higher in vitro transfection efficiency, stronger abilities to migrate to lymph nodes and stimulate dendritic cells maturation in vivo, which further led to potent humoral and cellular immune responses, and showed lower local and systemic toxicity than PEI25k/mRNA. These results demonstrate the potential of CD-PEI2k/mRNA nanocomplex as a self-adjuvanting vaccine delivery vehicle that traffics to lymph nodes with high efficiency. As we face outbreaks of pandemic diseases such as Zika virus, intranasal mRNA vaccination provides instant massive protection against highly variant viruses. Various polymer-based delivery systems have been successfully applied in intranasal vaccine delivery. However, the influence of molecular structure of the polymeric carriers on the lymph node trafficking and dendritic cell maturation is seldom studied for intranasal vaccination. Therefore, engineering polymer-based vaccine delivery system and elucidating the relationship between molecular structure and the intranasal delivery efficiency are essential for maximizing the immune responses. We hereby

Combinations of various CpG motifs cloned into plasmid backbone modulate and enhance protective immunity of viral replicon DNA anthrax vaccines.

PubMed

Yu, Yun-Zhou; Ma, Yao; Xu, Wen-Hui; Wang, Shuang; Sun, Zhi-Wei

2015-08-01

DNA vaccines are generally weak stimulators of the immune system. Fortunately, their efficacy can be improved using a viral replicon vector or by the addition of immunostimulatory CpG motifs, although the design of these engineered DNA vectors requires optimization. Our results clearly suggest that multiple copies of three types of CpG motifs or combinations of various types of CpG motifs cloned into a viral replicon vector backbone with strong immunostimulatory activities on human PBMC are efficient adjuvants for these DNA vaccines to modulate and enhance protective immunity against anthrax, although modifications with these different CpG forms in vivo elicited inconsistent immune response profiles. Modification with more copies of CpG motifs elicited more potent adjuvant effects leading to the generation of enhanced immunity, which indicated a CpG motif dose-dependent enhancement of antigen-specific immune responses. Notably, the enhanced and/or synchronous adjuvant effects were observed in modification with combinations of two different types of CpG motifs, which provides not only a contribution to the knowledge base on the adjuvant activities of CpG motifs combinations but also implications for the rational design of optimal DNA vaccines with combinations of CpG motifs as "built-in" adjuvants. We describe an efficient strategy to design and optimize DNA vaccines by the addition of combined immunostimulatory CpG motifs in a viral replicon DNA plasmid to produce strong immune responses, which indicates that the CpG-modified viral replicon DNA plasmid may be desirable for use as vector of DNA vaccines.

Strong-field adiabatic passage in the continuum: Electromagnetically induced transparency and stimulated Raman adiabatic passage

NASA Astrophysics Data System (ADS)

Eilam, A.; Shapiro, M.

2012-01-01

We present a fully quantum-mechanical theory of the mutual light-matter effects when two laser pulses interact with three discrete states coupled to a (quasi)continuum. Our formulation uses a single set of equations to describe the time dependence of the discrete and continuum populations, as well as pulse propagation in electromagnetically induced transparency (EIT) and stimulated Raman adiabatic passage (STIRAP) situations, for both weak and strong laser pulses. The theory gives a mechanistic picture of the “slowing down of light” and the state of spontaneously emitted photons during this process. Surprising features regarding the time dependence of material and radiative transients as well as limitations on quantum light storage and retrieval are unraveled.

Epidemiological and economic impact of pandemic influenza in Chicago: Priorities for vaccine interventions

PubMed Central

Dorratoltaj, Nargesalsadat; Marathe, Achla; Swarup, Samarth; Eubank, Stephen G.

2017-01-01

The study objective is to estimate the epidemiological and economic impact of vaccine interventions during influenza pandemics in Chicago, and assist in vaccine intervention priorities. Scenarios of delay in vaccine introduction with limited vaccine efficacy and limited supplies are not unlikely in future influenza pandemics, as in the 2009 H1N1 influenza pandemic. We simulated influenza pandemics in Chicago using agent-based transmission dynamic modeling. Population was distributed among high-risk and non-high risk among 0–19, 20–64 and 65+ years subpopulations. Different attack rate scenarios for catastrophic (30.15%), strong (21.96%), and moderate (11.73%) influenza pandemics were compared against vaccine intervention scenarios, at 40% coverage, 40% efficacy, and unit cost of $28.62. Sensitivity analysis for vaccine compliance, vaccine efficacy and vaccine start date was also conducted. Vaccine prioritization criteria include risk of death, total deaths, net benefits, and return on investment. The risk of death is the highest among the high-risk 65+ years subpopulation in the catastrophic influenza pandemic, and highest among the high-risk 0–19 years subpopulation in the strong and moderate influenza pandemics. The proportion of total deaths and net benefits are the highest among the high-risk 20–64 years subpopulation in the catastrophic, strong and moderate influenza pandemics. The return on investment is the highest in the high-risk 0–19 years subpopulation in the catastrophic, strong and moderate influenza pandemics. Based on risk of death and return on investment, high-risk groups of the three age group subpopulations can be prioritized for vaccination, and the vaccine interventions are cost saving for all age and risk groups. The attack rates among the children are higher than among the adults and seniors in the catastrophic, strong, and moderate influenza pandemic scenarios, due to their larger social contact network and homophilous interactions

Low-dose priming before vaccination with the phase I chloroform-methanol residue vaccine against Q fever enhances humoral and cellular immune responses to Coxiella burnetii.

PubMed

Waag, David M; England, Marilyn J; Bolt, Christopher R; Williams, Jim C

2008-10-01

Although the phase I Coxiella burnetii cellular vaccine is completely efficacious in humans, adverse local and systemic reactions may develop if immune individuals are inadvertently vaccinated. The phase I chloroform-methanol residue (CMRI) vaccine was developed as a potentially safer alternative. Human volunteers with no evidence of previous exposure to C. burnetii received a subcutaneous vaccination with the CMRI vaccine in phase I studies under protocol IND 3516 to evaluate the safety and immunogenicity of the vaccine. This clinical trial tested escalating doses of the CMRI vaccine, ranging from 0.3 to 60 microg, followed by a booster dose of 30 microg, in a placebo-controlled study. Although priming doses of the CMRI vaccine did not induce a specific antibody detectable by enzyme-linked immunosorbent assay, booster vaccination stimulated the production of significant levels of anti-C. burnetii antibody. Peripheral blood cells (PBCs) of vaccinees responded to C. burnetii cellular antigen in vitro in a vaccine dose-dependent manner. After the booster dose, PBCs were activated by recall antigen in vitro, regardless of the priming dose. These findings suggest that vaccination with the CMRI vaccine can effectively prime the immune system to mount significant anamnestic responses after infection.

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

Impact of cytokine in type 1 narcolepsy: Role of pandemic H1N1 vaccination ?

PubMed

Lecendreux, Michel; Libri, Valentina; Jaussent, Isabelle; Mottez, Estelle; Lopez, Régis; Lavault, Sophie; Regnault, Armelle; Arnulf, Isabelle; Dauvilliers, Yves

2015-06-01

Recent advances in the identification of susceptibility genes and environmental exposures (pandemic influenza 2009 vaccination) provide strong support that narcolepsy type 1 is an immune-mediated disease. Considering the limited knowledge regarding the immune mechanisms involved in narcolepsy whether related to flu vaccination or not and the recent progresses in cytokine measurement technology, we assessed 30 cytokines, chemokines and growth factors using the Luminex technology in either peripheral (serum) or central (CSF) compartments in a large population of 90 children and adult patients with narcolepsy type 1 in comparison to 58 non-hypocretin deficient hypersomniacs and 41 healthy controls. Furthermore, we compared their levels in patients with narcolepsy whether exposed to pandemic flu vaccine or not, and analyzed the effect of age, duration of disease and symptom severity. Comparison for sera biomarkers between narcolepsy (n = 84, 54 males, median age: 15.5 years old) and healthy controls (n = 41, 13 males, median age: 20 years old) revealed an increased stimulation of the immune system with high release of several pro- and anti-inflammatory serum cytokines and growth factors with interferon-γ, CCL11, epidermal growth factor, and interleukin-2 receptor being independently associated with narcolepsy. Increased levels of interferon-γ, CCL11, and interleukin-12 were found when close to narcolepsy onset. After several adjustments, only one CSF biomarker differed between narcolepsy (n = 44, 26 males, median age: 15 years old) and non-hypocretin deficient hypersomnias (n = 57, 24 males, median age: 36 years old) with higher CCL 3 levels found in narcolepsy. Comparison for sera biomarkers between patients with narcolepsy who developed the disease post-pandemic flu vaccination (n = 36) to those without vaccination (n = 48) revealed an increased stimulation of the immune system with high release of three cytokines, regulated upon activation normal T-cell expressed

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.

Leishmaniasis vaccines: past, present and future.

PubMed

Modabber, Farrokh

2010-11-01

No vaccine exists against any form of leishmaniasis. Because recovery from infection is usually accompanied by a strong immunity and because it is possible to protect experimental animals against live challenge, hope for the development of a vaccine for humans has been high. However, leishmaniasis is a disease of the poor and the market for a vaccine is very limited. Until a few years ago, with minimal resources, only a pragmatic approach was possible for testing the first-generation vaccines (i.e. killed whole parasites). Recently, funding has become available for developing defined second-generation vaccines, including recombinant proteins and DNA constructs. With new adjuvants also being developed there is new hope, and several new vaccines are in development against leishmaniasis. Copyright © 2010 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Increasing Coverage of Hepatitis B Vaccination in China

PubMed Central

Wang, Shengnan; Smith, Helen; Peng, Zhuoxin; Xu, Biao; Wang, Weibing

2016-01-01

Abstract This study used a system evaluation method to summarize China's experience on improving the coverage of hepatitis B vaccine, especially the strategies employed to improve the uptake of timely birth dosage. Identifying successful methods and strategies will provide strong evidence for policy makers and health workers in other countries with high hepatitis B prevalence. We conducted a literature review included English or Chinese literature carried out in mainland China, using PubMed, the Cochrane databases, Web of Knowledge, China National Knowledge Infrastructure, Wanfang data, and other relevant databases. Nineteen articles about the effectiveness and impact of interventions on improving the coverage of hepatitis B vaccine were included. Strong or moderate evidence showed that reinforcing health education, training and supervision, providing subsidies for facility birth, strengthening the coordination among health care providers, and using out-of-cold-chain storage for vaccines were all important to improving vaccination coverage. We found evidence that community education was the most commonly used intervention, and out-reach programs such as out-of-cold chain strategy were more effective in increasing the coverage of vaccination in remote areas where the facility birth rate was respectively low. The essential impact factors were found to be strong government commitment and the cooperation of the different government departments. Public interventions relying on basic health care systems combined with outreach care services were critical elements in improving the hepatitis B vaccination rate in China. This success could not have occurred without exceptional national commitment. PMID:27175710

A Randomized Controlled Trial to Evaluate a Potential Hepatitis B Booster Vaccination Strategy Using Combined Hepatitis A and B Vaccine.

PubMed

Li, Fangjun; Hu, Yuansheng; Zhou, Youming; Chen, Lixin; Xia, Wei; Song, Yufei; Tan, Zhengliang; Gao, Lidong; Yang, Zhong; Zeng, Gang; Han, Xing; Li, Junhua; Li, Jing

2017-05-01

Booster doses could play a major role in no responders or low responders to primary hepatitis B (HB) vaccine. Planed time point for hepatitis A vaccination in China provides a good opportunity to carry out HB booster dose by using combined hepatitis A and B vaccine. A randomized, double-blinded clinical trial was conducted to compare the immunogenicity and safety of toddlers 18-24 months of age receiving 3 different vaccination regimens: 2 doses of inactivated hepatitis A vaccine (group 1), 1 dose of inactivated hepatitis A vaccine plus 1 dose of combined hepatitis A and B vaccine (group 2) or 2 doses of combined hepatitis A and B vaccine (group 3). All 3 groups showed 100% seroprotection for antihepatitis A virus antibody after vaccination. Seroprotection rate for anti-HB antibody before vaccination ranged from 79.5% to 92.9% in the 3 groups. After second inoculation, anti-HBs seroprotection increased from 92.9% to 100% in group 2 with postvaccination geometric mean concentration (GMC) of 2258.3 mIU/mL and from 79.5% to 98.9% in group 3 with postvaccination GMC of 2055.3 mIU/mL. The adverse events were not statistically different among groups (P = 0.345). Combined hepatitis A and B vaccine could stimulate high level of both antihepatitis A virus and anti-HBs antibodies and not increase adverse events, providing a new choice for HB booster.

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.

Learning immunology from the yellow fever vaccine: innate immunity to systems vaccinology.

PubMed

Pulendran, Bali

2009-10-01

Despite their great success, we understand little about how effective vaccines stimulate protective immune responses. Two recent developments promise to yield such understanding: the appreciation of the crucial role of the innate immune system in sensing microorganisms and tuning immune responses, and advances in systems biology. Here I review how these developments are yielding insights into the mechanism of action of the yellow fever vaccine, one of the most successful vaccines ever developed, and the broader implications for vaccinology.

We strongly support childhood immunisation-statement from the European Academy of Paediatrics (EAP).

PubMed

Dornbusch, Hans Juergen; Hadjipanayis, Adamos; Del Torso, Stefano; Mercier, Jean-Christophe; Wyder, Corinne; Schrier, Lenneke; Ross-Russell, Robert; Stiris, Tom; Ludvigsson, Jonas F

2017-05-01

The eradication of smallpox and the elimination of several other infectious diseases from much of the world has provided convincing evidence that vaccines are among the most effective interventions for promoting health. The current scepticism about immunisation among members of the new US administration carries a risk of decreasing immunisation rates also in Europe. While only a small minority of the population are strongly anti-vaccine, their public activities have significantly influenced an uncertainty among the general population about both the safety of and the necessity for vaccination. Therefore, the EAP calls for greater publically available, scientifically supported information on vaccination, particularly targeted at health care providers, for the further development of electronically based immunisation information systems (IIS). We further call on all European countries to work together both in legislative and public health arenas in order to increase vaccination coverage among the paediatric population. In the interest of children and their parents, the EAP expresses its strong support for childhood immunisation and recommended vaccination schedules. We are prepared to work with governments and media and share the extensive evidence demonstrating the effectiveness and safety of vaccines.

Herpes zoster caused by vaccine-strain varicella zoster virus in an immunocompetent recipient of zoster vaccine.

PubMed

Tseng, Hung Fu; Schmid, D Scott; Harpaz, Rafael; LaRussa, Philip; Jensen, Nancy J; Rivailler, Pierre; Radford, Kay; Folster, Jennifer; Jacobsen, Steven J

2014-04-01

We report the first laboratory-documented case of herpes zoster caused by the attenuated varicella zoster virus (VZV) contained in Zostavax in a 68-year-old immunocompetent adult with strong evidence of prior wild-type VZV infection. The complete genome sequence of the isolate revealed that the strain carried 15 of 42 (36%) recognized varicella vaccine-associated single-nucleotide polymorphisms, including all 5 of the fixed vaccine markers present in nearly all of the strains in the vaccine. The case of herpes zoster was relatively mild and resolved without complications.

Inspecting the Mechanism: A Longitudinal Analysis of Socioeconomic Status Differences in Perceived Influenza Risks, Vaccination Intentions, and Vaccination Behaviors during the 2009-2010 Influenza Pandemic.

PubMed

Maurer, Jürgen

2016-10-01

Influenza vaccination is strongly associated with socioeconomic status, but there is only limited evidence on the respective roles of socioeconomic differences in vaccination intentions versus corresponding differences in follow-through on initial vaccination plans for subsequent socioeconomic differences in vaccine uptake. Nonparametric mean smoothing, linear regression, and probit models were used to analyze longitudinal survey data on perceived influenza risks, behavioral vaccination intentions, and vaccination behavior of adults during the 2009-2010 influenza A/H1N1 ("swine flu") pandemic in the United States. Perceived influenza risks and behavioral vaccination intentions were elicited prior to the availability of H1N1 vaccine using a probability scale question format. H1N1 vaccine uptake was assessed at the end of the pandemic. Education, income, and health insurance coverage displayed positive associations with behavioral intentions to get vaccinated for pandemic influenza while employment was negatively associated with stated H1N1 vaccination intentions. Education and health insurance coverage also displayed significant positive associations with pandemic vaccine uptake. Moreover, behavioral vaccination intentions showed a strong and statistically significant positive partial association with later H1N1 vaccination. Incorporating vaccination intentions in a statistical model for H1N1 vaccine uptake further highlighted higher levels of follow-through on initial vaccination plans among persons with higher education levels and health insurance. Sampling bias, misreporting in self-reported data, and limited generalizability to nonpandemic influenza are potential limitations of the analysis. Closing the socioeconomic gap in influenza vaccination requires multipronged strategies that not only increase vaccination intentions by improving knowledge, attitudes, and beliefs but also facilitate follow-through on initial vaccination plans by improving behavioral

Inspecting the Mechanism: A Longitudinal Analysis of Socioeconomic Status Differences in Perceived Influenza Risks, Vaccination Intentions and Vaccination Behaviors during the 2009-2010 Influenza Pandemic

PubMed Central

Maurer, Jürgen

2015-01-01

Background Influenza vaccination is strongly associated with socioeconomic status, but there is only limited evidence on the respective roles of socioeconomic differences in vaccination intentions vs. corresponding differences in follow through on initial vaccination plans for subsequent socioeconomic differences in vaccine uptake. Methods Nonparametric mean smoothing, linear regression and Probit models were used to analyze longitudinal survey data on perceived influenza risks, behavioral vaccination intentions and vaccination behavior of adults during the 2009-10 influenza A/H1N1 (“Swine Flu”) pandemic in the United States. Perceived influenza risks and behavioral vaccination intentions were elicited prior to the availability of H1N1 vaccine using a probability scale question format. H1N1 vaccine uptake was assessed at the end of the pandemic. Results Education, income and health insurance coverage displayed positive associations with behavioral intentions to get vaccinated for pandemic influenza while employment was negatively associated with stated H1N1 vaccination intentions. Education and health insurance coverage also displayed significant positive associations with pandemic vaccine uptake. Moreover, behavioral vaccination intentions showed a strong and statistically significant positive partial association with later H1N1 vaccination. Incorporating vaccination intentions in a statistical model for H1N1 vaccine uptake further highlighted higher levels of follow through on initial vaccination plans among persons with higher education levels and health insurance. Limitations Sampling bias, misreporting in self-reported data, and limited generalizability to non-pandemic influenza are potential limitations of the analysis. Conclusions Closing the socioeconomic gap in influenza vaccination requires multi-pronged strategies that not only increase vaccination intentions by improving knowledge, attitudes and beliefs but also facilitate follow through on initial

Impact of imitation processes on the effectiveness of ring vaccination.

PubMed

Wells, Chad R; Tchuenche, Jean M; Meyers, Lauren Ancel; Galvani, Alison P; Bauch, Chris T

2011-11-01

Ring vaccination can be a highly effective control strategy for an emerging disease or in the final phase of disease eradication, as witnessed in the eradication of smallpox. However, the impact of behavioural dynamics on the effectiveness of ring vaccination has not been explored in mathematical models. Here, we analyze a series of stochastic models of voluntary ring vaccination. Contacts of an index case base vaccinating decisions on their own individual payoffs to vaccinate or not vaccinate, and they can also imitate the behaviour of other contacts of the index case. We find that including imitation changes the probability of containment through ring vaccination considerably. Imitation can cause a strong majority of contacts to choose vaccination in some cases, or to choose non-vaccination in other cases-even when the equivalent solution under perfectly rational (non-imitative) behaviour yields mixed choices. Moreover, imitation processes can result in very different outcomes in different stochastic realizations sampled from the same parameter distributions, by magnifying moderate tendencies toward one behaviour or the other: in some realizations, imitation causes a strong majority of contacts not to vaccinate, while in others, imitation promotes vaccination and reduces the number of secondary infections. Hence, the effectiveness of ring vaccination can depend significantly and unpredictably on imitation processes. Therefore, our results suggest that risk communication efforts should be initiated early in an outbreak when ring vaccination is to be applied, especially among subpopulations that are heavily influenced by peer opinions.

Calcium phosphate coupled Newcastle disease vaccine elicits humoral and cell mediated immune responses in chickens.

PubMed

Koppad, Sanganagouda; Raj, G Dhinakar; Gopinath, V P; Kirubaharan, J John; Thangavelu, A; Thiagarajan, V

2011-12-01

Calcium phosphate (CaP) particles were coupled with inactivated Newcastle disease virus (NDV) vaccine. The surface morphology of CaP particles coupled to NDV was found to be spherical, smooth and with a tendency to agglomerate. The mean (± SE) size of CaP particles was found 557.44 ± 18.62 nm. The mean percent encapsulation efficiency of CaP particles coupled to NDV assessed based on total protein content and haemagglutination (HA) activity in eluate was found to be 10.72 ± 0.89 and 12.50 ± 2.09, respectively. The humoral and cell mediated immune responses induced by CaP coupled NDV vaccine were assessed in comparison to a commercial live vaccine (RDV 'F'). CaP coupled NDV vaccine elicited prolonged haemagglutination inhibition (HI) and enzyme linked immunosorbent assay (ELISA) titres in the serum even at fourth and fifth week post-vaccination (PV), unlike RDV 'F' inoculated chickens whose titres declined to insignificant levels by this time. CaP coupled NDV vaccine could stimulate HI antibodies in tracheal washings and tears from second and first week PV, respectively. IgA ELISA antibodies were also seen in tracheal washings of these birds from third week PV and in tears from second week PV. CaP coupled NDV vaccine elicited cell mediated immune responses (CMI) from two to four weeks PV. The stimulation indices obtained after stimulation with specific antigen was not significantly different between CaP coupled antigen and live NDV virus except on first week PV. However, CaP coupled antigen did not cause suppression of lympo proliferation as indicated by statistically similar responses to mitogen, concanavalin A between the two groups. Overall, CaP coupled NDV vaccine elicited stronger and prolonged immune responses in comparison to the commercial live vaccine. No increase in the serum calcium and phosphorous levels were seen in CaP coupled NDV vaccine inoculated chickens. Copyright © 2010 Elsevier Ltd. All rights reserved.

Identification of L. infantum chagasi proteins in VL patients' urine: a promising antigen discovery approach of vaccine candidates

PubMed Central

Kashino, Suely S.; Abeijon, Claudia; Qin, Lizeng; Kanunfre, Kelly A.; Kubrusly, Flávia S.; Silva, Fernando O.; Costa, Dorcas L.; Campos, Dioclécio; Costa, Carlos H.N.; Raw, Isaias; Campos-Neto, Antonio

2012-01-01

Visceral leishmaniasis (VL) is a serious lethal parasitic disease caused by Leishmania donovani in Asia and by Leishmania infantum chagasi in Southern Europe and South America. VL is endemic in 47 countries with an annual incidence estimated to be 500,000 cases. This high incidence is due in part to the lack of an efficacious vaccine. Here, we introduce an innovative approach to directly identify parasite vaccine candidate antigens that are abundantly produced in vivo in humans with VL. We combined RP-HPLC and mass spectrometry and categorized three L. infantum chagasi proteins, presumably produced in spleen, liver, and bone marrow lesions and excreted in the patients’ urine. Specifically, these proteins were the following: Li-isd1 (XP_001467866.1), Li-txn1 (XP_001466642.1), and Li-ntf2 (XP_001463738.1). Initial vaccine validation studies were performed with the rLi-ntf2 protein produced in E. coli mixed with the adjuvant BpMPLA-SE. This formulation stimulated potent Th1 response in BALB/c mice. Compared to control animals, mice immunized with Li-ntf2 + BpMPLASE had a marked parasite burden reduction in spleens at 40 days post-challenge with virulent L. infantum chagasi. These results strongly support the proposed antigen discovery strategy of vaccine candidates to kala-azar and opens novel possibilities for vaccine development to other serious infectious diseases. PMID:22443237

Physician Knowledge and Attitudes About Hepatitis A and Current Practices Regarding Hepatitis A Vaccination Delivery.

PubMed

Nelson, Noele P; Allison, Mandy A; Lindley, Megan C; Brtnikova, Michaela; Crane, Lori A; Beaty, Brenda L; Hurley, Laura P; Kempe, Allison

2017-07-01

To assess physicians': 1) knowledge and attitudes about hepatitis A disease and hepatitis A (HepA) vaccine, 2) child care and school HepA vaccine mandates, 3) practices related to HepA vaccine delivery, 4) factors associated with strongly recommending HepA vaccine to all 1- to 2-year-olds, and 5) feasibility of implementing HepA catch-up vaccination at health maintenance visits. A national survey was conducted among representative networks of pediatricians and family medicine physicians (FMs) from March to June, 2014 via e-mail or mail on the basis of provider preference. Response rates were 81% (356 of 440) among pediatricians and 75% (348 of 464) among FMs. Less than 50% correctly identified that hepatitis A virus (HAV) infection is usually asymptomatic in young children and that morbidity from HAV disease increases with age. Ninety-two percent of pediatricians and 59% of FMs strongly recommend HepA vaccine for all 1- to 2-year-olds. In addition to practice specialty, belief that HepA vaccine is required for kindergarten enrollment was the most robust predictor of strong physician recommendation. Gaps in knowledge regarding HAV infection and hepatitis A recommendations and lack of a strong recommendation for routine HepA vaccination of young children among FMs likely contribute to suboptimal coverage. Closing knowledge gaps and addressing barriers that prevent all physicians from strongly recommending HepA vaccine to 1- to 2-year-olds could help increase HepA vaccine coverage and ultimately improve population protection against HAV infection. Published by Elsevier Inc.

Developing an Inactivated Rotavirus Vaccine and Evaluating the Immunogenicity Against a Commercially Available Attenuated Rotavirus Vaccine Using a Mice Animal Model.

PubMed

Hashim, Ayaa S M; Aboshanab, Khaled M A; El-Sayed, Aly F M

2016-12-01

There is a high demand for public immunization against Rotavirus (RV), especially in Africa. In Africa, the attenuated RV vaccination is contraindicated in patients with immune diseases and nutrition deficiency. Therefore, the inactivated RV vaccine (IRVV) could be an alternative. In this study, we aimed to develop a pentavalent-IRVV using the most circulating RV strains in Egypt and evaluate it against the commercially available Rotarix ® vaccine. Trial-IRVV was developed with 5% sucrose, 2% polysorbate-80, and adsorbed on Alum to potentiate the vaccine immune response. Then, it was injected subcutaneously into mice groups at 0-, 21-, and 35-time intervals. In parallel, Rotarix was administered twice on 0 and 28 th day. The success of the pentavalent-IRVV/monovalent-Rotarix vaccine immunity rested on achieving immunoglobulin G (IgG) exceeding 1:6,400 that implies less susceptibility to RV infection (RVI). IRVV stimulating IgG >1:6,400 could be an alternative vaccination approach to reach a reasonable protective immunization level against RVI. In addition, Alum adjuvant incorporation effectively provoked a triple elevation of the immunization pattern.

Vaccines for viral diseases with dermatologic manifestations.

PubMed

Brentjens, Mathijs H; Yeung-Yue, Kimberly A; Lee, Patricia C; Tyring, Stephen K

2003-04-01

Vaccines against infectious diseases have been available since the 1800s, when an immunization strategy against smallpox developed by Jenner gained wide acceptance. Until recently, the only vaccination strategies available involved the use of protein-based, whole killed, and attenuated live virus vaccines. These strategies have led to the development of effective vaccines against a variety of diseases with primary or prominent cutaneous manifestations. Effective and safe vaccines now used worldwide include those directed against measles and rubella (now commonly used together with a mumps vaccine as the trivalent MMR), chickenpox, and hepatitis B. The eradication of naturally occurring smallpox remains one of the greatest successes in the history of modern medicine, but stockpiles of live smallpox exist in the United States and Russia. Renewed interest in the smallpox vaccine reflects concerns about a possible bioterrorist threat using this virus. Yellow fever is a hemorrhagic virus endemic to tropical areas of South America and Africa. An effective vaccine for this virus has existed since 1937, and it is used widely in endemic areas of South America, and to a lesser extent in Africa. This vaccine is recommended once every 10 years for people who are traveling to endemic areas. Advances in immunology have led to a greater understanding of immune system function in viral diseases. Progress in genetics and molecular biology has allowed researchers to design vaccines with novel mechanisms of action (eg, DNA, vector, and VLP vaccines). Vaccines have also been designed to specifically target particular viral components, allowing for stimulation of various arms of the immune system as desired. Ongoing research shows promise in prophylactic and therapeutic vaccination for viral infections with cutaneous manifestations. Further studies are necessary before vaccines for HSV, HPV, and HIV become commercially available.

Relation between experimental and non-experimental study designs. HB vaccines: a case study.

PubMed

Jefferson, T; Demicheli, V

1999-01-01

To examine the relation between experimental and non-experimental study design in vaccinology. Assessment of each study design's capability of testing four aspects of vaccine performance, namely immunogenicity (the capacity to stimulate the immune system), duration of immunity conferred, incidence and seriousness of side effects, and number of infections prevented by vaccination. Experimental and non-experimental studies on hepatitis B (HB) vaccines in the Cochrane Vaccines Field Database. Experimental and non-experimental vaccine study designs are frequently complementary but some aspects of vaccine quality can only be assessed by one of the types of study. More work needs to be done on the relation between study quality and its significance in terms of effect size.

Forging a potent vaccine adjuvant: CpG ODN/cationic peptide nanorings.

PubMed

Gungor, Bilgi; Yagci, Fuat Cem; Gursel, Ihsan; Gursel, Mayda

Type I interferon inducers may potentially be engineered to function as antiviral and anticancer agents, or alternatively, vaccine adjuvants, all of which may have clinical applications. We recently described a simple strategy to convert a Toll-like receptor 9 (TLR9) agonist devoid of interferon α (IFNα) stimulating activity into a robust Type I interferon inducer with potent vaccine adjuvant activity.

HPV vaccine: immersed in controversy.

PubMed

Ohri, Linda K

2007-11-01

There has been substantial media coverage of the quadrivalent human papillomavirus (HPV) vaccine since the Food and Drug Administration approved Gardasil (Merck & Co., Inc.) on June 8, 2006. The most vocal complaints maintain that its use will promote promiscuity among teenagers, and condemn proposed mandated use for school entry. Some also question evidence for the vaccine's safety. There have been concerns raised by both providers and patients regarding financial barriers to access. Still others argue that additional populations could benefit who have not been included in current recommendations. Clarification of these issues is essential to advance optimal use of this important new vaccine. There is strong evidence to support HPV vaccine as an effective, safe, and efficient public health measure. School mandates are valuable tools to reduce disparities in availability of immunizations. The time has come to consider universal funding as a means to improve access to all recommended vaccines.

MUC1-specific immune therapy generates a strong anti-tumor response in a MUC1-tolerant colon cancer model.

PubMed

Mukherjee, P; Pathangey, L B; Bradley, J B; Tinder, T L; Basu, G D; Akporiaye, E T; Gendler, S J

2007-02-19

A MUC1-based vaccine was used in a preclinical model of colon cancer. The trial was conducted in a MUC1-tolerant immune competent host injected with MC38 colon cancer cells expressing MUC1. The vaccine included: MHC class I-restricted MUC1 peptides, MHC class II-restricted pan-helper-peptide, unmethylated CpG oligodeoxynucleotide, and granulocyte macrophage-colony stimulating factor. Immunization was successful in breaking MUC1 self-tolerance, and in eliciting a robust anti-tumor response. The vaccine stimulated IFN-gamma-producing CD4(+) helper and CD8(+) cytotoxic T cells against MUC1 and other undefined MC38 tumor antigens. In the prophylactic setting, immunization caused complete rejection of tumor cells, while in the therapeutic regimen, tumor burden was significantly reduced.

Prolonging herd immunity to cholera via vaccination: Accounting for human mobility and waning vaccine effects

PubMed Central

Buckee, Caroline O.

2018-01-01

Background Oral cholera vaccination is an approach to preventing outbreaks in at-risk settings and controlling cholera in endemic settings. However, vaccine-derived herd immunity may be short-lived due to interactions between human mobility and imperfect or waning vaccine efficacy. As the supply and utilization of oral cholera vaccines grows, critical questions related to herd immunity are emerging, including: who should be targeted; when should revaccination be performed; and why have cholera outbreaks occurred in recently vaccinated populations? Methods and findings We use mathematical models to simulate routine and mass oral cholera vaccination in populations with varying degrees of migration, transmission intensity, and vaccine coverage. We show that migration and waning vaccine efficacy strongly influence the duration of herd immunity while birth and death rates have relatively minimal impacts. As compared to either periodic mass vaccination or routine vaccination alone, a community could be protected longer by a blended “Mass and Maintain” strategy. We show that vaccination may be best targeted at populations with intermediate degrees of mobility as compared to communities with very high or very low population turnover. Using a case study of an internally displaced person camp in South Sudan which underwent high-coverage mass vaccination in 2014 and 2015, we show that waning vaccine direct effects and high population turnover rendered the camp over 80% susceptible at the time of the cholera outbreak beginning in October 2016. Conclusions Oral cholera vaccines can be powerful tools for quickly protecting a population for a period of time that depends critically on vaccine coverage, vaccine efficacy over time, and the rate of population turnover through human mobility. Due to waning herd immunity, epidemics in vaccinated communities are possible but become less likely through complementary interventions or data-driven revaccination strategies. PMID:29489815

Microneedle-based vaccines

PubMed Central

Prausnitz, Mark R.; Mikszta, John A.; Cormier, Michel; Andrianov, Alexander K.

2010-01-01

The threat of pandemic influenza and other public health needs motivates development of better vaccine delivery systems. To address this need, microneedles have been developed as micron-scale needles fabricated using low-cost manufacturing methods that administer vaccine into the skin using a simple device that may be suitable for self-administration. Delivery using solid or hollow microneedles can be accomplished by (i) piercing the skin and then applying a vaccine formulation or patch onto the permeabilized skin, (ii) coating or encapsulating vaccine onto or within microneedles for rapid, or delayed, dissolution and release in the skin and (iii) injection into the skin using a modified syringe or pump. Extensive clinical experience with smallpox, TB and other vaccines has shown that vaccine delivery into the skin using conventional intradermal injection is generally safe and effective and often elicits the same immune responses at lower doses compared to intramuscular injection. Animal experiments using microneedles have shown similar benefits. Microneedles have been used to deliver whole, inactivated virus; trivalent split antigen vaccines; and DNA plasmid encoding the influenza hemagglutinin to rodents and found strong antibody responses. In addition, ChimeriVax™-JE against yellow fever was administered to non-human primates and generated protective levels of neutralizing antibodies more than seven times greater than subcutaneous delivery; DNA plasmid encoding hepatitis B surface antigen was administered to mice and generated antibody and T cell responses at least as strong as hypodermic injections; recombinant Protective Antigen of Baccilus anthracis was administered to rabbits and provided complete protection from lethal aerosol anthrax spore challenge at a lower dose than intramuscular injection; and DNA plasmid encoding four vaccinia virus genes administered to mice in combination with electroporation generated neutralizing antibodies that apparently

Improving Physician Recommendations for Human Papillomavirus Vaccination: The Role of Professional Organizations.

PubMed

Hswen, Yulin; Gilkey, Melissa B; Rimer, Barbara K; Brewer, Noel T

2017-01-01

To address low human papillomavirus (HPV) vaccination coverage, the American Academy of Family Physicians (AAFP) and the American Academy of Pediatrics (AAP) have launched national campaigns encouraging physicians to deliver strong HPV vaccine recommendations. We surveyed family physicians and pediatricians to examine the impact of these efforts on physicians' recommendation practices. A national sample of family physicians and pediatricians (n = 776) completed our online survey in 2014. The survey assessed reach, content, and influence of AAFP and AAP communications about HPV vaccination. The survey also assessed quality of physicians' communication practices for recommending HPV vaccination. Forty-seven percent of family physicians reported receiving information on HPV vaccination from AAFP, whereas 62% of pediatricians reported receiving information from AAP. Among physicians reached by AAFP or AAP, most reported receiving the message to give strong recommendations to adolescent boys (71%) and girls (78%). Although receiving information was not associated with HPV vaccine recommendation quality, receiving the message to give strong recommendations correlated with delivering higher-quality recommendations for boys (odds ratio, 4.19, 95% confidence interval, 2.64-6.64) and girls (odds ratio, 3.15, 95% confidence interval, 1.91-5.18). Over half of physicians reported improving their HPV vaccine communication after receiving information from AAFP (69%) or AAP (53%). Our findings suggest that it is important for AAFP and AAP to communicate the need for strong HPV vaccine recommendations. Given that many physicians reported improving their recommendation practices, professional organizations stand to contribute to increasing HPV vaccination coverage, but they will likely need to increase the intensity of quality improvement efforts to do so.

In vivo production of a novel glycoconjugate vaccine against Shigella flexneri 2a in recombinant Escherichia coli: identification of stimulating factors for in vivo glycosylation.

PubMed

Kämpf, Michael M; Braun, Martin; Sirena, Dominique; Ihssen, Julian; Thöny-Meyer, Linda; Ren, Qun

2015-01-23

Glycoconjugated vaccines composed of polysaccharide antigens covalently linked to immunogenic carrier proteins have proved to belong to the most effective and safest vaccines for combating bacterial pathogens. The functional transfer of the N-glycosylation machinery from Campylobacter jejuni to the standard prokaryotic host Escherichia coli established a novel bioconjugation methodology termed bacterial glycoengineering. In this study, we report on the production of a new recombinant glycoconjugate vaccine against Shigella flexneri 2a representing the major serotype for global outbreaks of shigellosis. We demonstrate that S. flexneri 2a O-polysaccharides can be transferred to a detoxified variant of Pseudomonas aeruginosa carrier protein exotoxin A (EPA) by the C. jejuni oligosaccharyltransferase PglB, resulting in glycosylated EPA-2a. Moreover, we optimized the in vivo production of this novel vaccine by identification and quantitative analysis of critical process parameters for glycoprotein synthesis. It was found that sequential induction of oligosaccharyltransferase PglB and carrier protein EPA increased the specific productivity of EPA-2a by a factor of 1.6. Furthermore, by the addition of 10 g/L of the monosaccharide N-acetylglucosamine during induction, glycoconjugate vaccine yield was boosted up to 3.1-fold. The optimum concentration of Mg2+ ions for N-glycan transfer was determined to be 10 mM. Finally, optimized parameters were transferred to high cell density cultures with a 46-fold increase of overall yield of glycoconjugate compared to the one in initial shake flask production. The present study is the first attempt to identify stimulating parameters for improved productivity of S. flexneri 2a bioconjugates. Optimization of glycosylation efficiency will ultimately foster the transfer of lab-scale expression to a cost-effective in vivo production process for a glycoconjugate vaccine against S. flexneri 2a in E. coli. This study is an important step

Low-Dose Priming before Vaccination with the Phase I Chloroform-Methanol Residue Vaccine against Q Fever Enhances Humoral and Cellular Immune Responses to Coxiella burnetii▿

PubMed Central

Waag, David M.; England, Marilyn J.; Bolt, Christopher R.; Williams, Jim C.

2008-01-01

Although the phase I Coxiella burnetii cellular vaccine is completely efficacious in humans, adverse local and systemic reactions may develop if immune individuals are inadvertently vaccinated. The phase I chloroform-methanol residue (CMRI) vaccine was developed as a potentially safer alternative. Human volunteers with no evidence of previous exposure to C. burnetii received a subcutaneous vaccination with the CMRI vaccine in phase I studies under protocol IND 3516 to evaluate the safety and immunogenicity of the vaccine. This clinical trial tested escalating doses of the CMRI vaccine, ranging from 0.3 to 60 μg, followed by a booster dose of 30 μg, in a placebo-controlled study. Although priming doses of the CMRI vaccine did not induce a specific antibody detectable by enzyme-linked immunosorbent assay, booster vaccination stimulated the production of significant levels of anti-C. burnetii antibody. Peripheral blood cells (PBCs) of vaccinees responded to C. burnetii cellular antigen in vitro in a vaccine dose-dependent manner. After the booster dose, PBCs were activated by recall antigen in vitro, regardless of the priming dose. These findings suggest that vaccination with the CMRI vaccine can effectively prime the immune system to mount significant anamnestic responses after infection. PMID:18701647

Novel immunotherapy vaccine development.

PubMed

Jutel, Marek; Akdis, Cezmi A

2014-12-01

Allergen-specific immunotherapy is the only curative treatment for allergic diseases. In spite of the great progress in both vaccine development and the methods of allergen immunotherapy (AIT) in recent years, several key problems related to limited efficacy, side-effects, low patient adherence and the relatively high costs due to the long duration (3-5 years) remain to be solved. The current approaches aiming at optimization of AIT are reviewed, including both conceptual studies in experimental models and proof-of-concept - as well as large, multicenter clinical studies. The most promising approaches to improve efficacy and safety of vaccine-based AIT include bypassing IgE binding and targeting allergen-specific T cells using hypoallergenic recombinant allergen derivatives and immunogenic peptides, the use of new adjuvants and stimulators of the innate immune response, the fusion of allergens to immune modifiers and peptide carrier proteins and new routes of vaccine administration. The cloning of allergen proteins and genetic engineering enabled the production of vaccines that have well defined molecular, immunologic and biologic characteristics as well as modified molecular structure. These new compounds along with new immunization protocols can bring us closer to the ultimate goal of AIT, that is, complete cure of a large number of allergic patients.

Recombinant adenovirus expressing the haemagglutinin of Peste des petits ruminants virus (PPRV) protects goats against challenge with pathogenic virus; a DIVA vaccine for PPR.

PubMed

Herbert, Rebecca; Baron, Jana; Batten, Carrie; Baron, Michael; Taylor, Geraldine

2014-02-26

Peste des petits ruminants virus (PPRV) is a morbillivirus that can cause severe disease in sheep and goats, characterised by pyrexia, pneumo-enteritis, and gastritis. The socio-economic burden of the disease is increasing in underdeveloped countries, with poor livestock keepers being affected the most. Current vaccines consist of cell-culture attenuated strains of PPRV, which induce a similar antibody profile to that induced by natural infection. Generation of a vaccine that enables differentiation of infected from vaccinated animals (DIVA) would benefit PPR control and eradication programmes, particularly in the later stages of an eradication campaign and for countries where the disease is not endemic. In order to create a vaccine that would enable infected animals to be distinguished from vaccinated ones (DIVA vaccine), we have evaluated the immunogenicity of recombinant fowlpox (FP) and replication-defective recombinant human adenovirus 5 (Ad), expressing PPRV F and H proteins, in goats. The Ad constructs induced higher levels of virus-specific and neutralising antibodies, and primed greater numbers of CD8+ T cells than the FP-vectored vaccines. Importantly, a single dose of Ad-H, with or without the addition of Ad expressing ovine granulocyte macrophage colony-stimulating factor and/or ovine interleukin-2, not only induced strong antibody and cell-mediated immunity but also completely protected goats against challenge with virulent PPRV, 4 months after vaccination. Replication-defective Ad-H therefore offers the possibility of an effective DIVA vaccine.

Antibody-Mediated and Cellular Immune Responses Induced in Naive Volunteers by Vaccination with Long Synthetic Peptides Derived from the Plasmodium vivax Circumsporozoite Protein

PubMed Central

Arévalo-Herrera, Myriam; Soto, Liliana; Perlaza, Blanca Liliana; Céspedes, Nora; Vera, Omaira; Lenis, Ana Milena; Bonelo, Anilza; Corradin, Giampietro; Herrera, Sócrates

2011-01-01

Plasmodium vivax circumsporozoite (CS) protein is a leading malaria vaccine candidate. We describe the characterization of specific immune responses induced in 21 malaria-naive volunteers vaccinated with long synthetic peptides derived from the CS protein formulated in Montanide ISA 720. Both antibody- and cell-mediated immune responses were analyzed. Antibodies were predominantly of IgG1 and IgG3 isotypes, recognized parasite proteins on the immunofluorescent antibody test, and partially blocked sporozoite invasion of hepatoma cell lines in vitro. Peripheral blood mononuclear cells from most volunteers (94%) showed IFN-γ production in vitro upon stimulation with both long signal peptide and short peptides containing CD8+ T-cell epitopes. The relatively limited sample size did not allow conclusions about HLA associations with the immune responses observed. In summary, the inherent safety and tolerability together with strong antibody responses, invasion blocking activity, and the IFN-γ production induced by these vaccine candidates warrants further testing in a phase II clinical trial. PMID:21292876

Intranasal DNA Vaccine for Protection against Respiratory Infectious Diseases: The Delivery Perspectives

PubMed Central

Xu, Yingying; Yuen, Pak-Wai; Lam, Jenny Ka-Wing

2014-01-01

Intranasal delivery of DNA vaccines has become a popular research area recently. It offers some distinguished advantages over parenteral and other routes of vaccine administration. Nasal mucosa as site of vaccine administration can stimulate respiratory mucosal immunity by interacting with the nasopharyngeal-associated lymphoid tissues (NALT). Different kinds of DNA vaccines are investigated to provide protection against respiratory infectious diseases including tuberculosis, coronavirus, influenza and respiratory syncytial virus (RSV) etc. DNA vaccines have several attractive development potential, such as producing cross-protection towards different virus subtypes, enabling the possibility of mass manufacture in a relatively short time and a better safety profile. The biggest obstacle to DNA vaccines is low immunogenicity. One of the approaches to enhance the efficacy of DNA vaccine is to improve DNA delivery efficiency. This review provides insight on the development of intranasal DNA vaccine for respiratory infections, with special attention paid to the strategies to improve the delivery of DNA vaccines using non-viral delivery agents. PMID:25014738

A Highly Immunogenic and Protective Middle East Respiratory Syndrome Coronavirus Vaccine Based on a Recombinant Measles Virus Vaccine Platform

PubMed Central

Malczyk, Anna H.; Kupke, Alexandra; Prüfer, Steffen; Scheuplein, Vivian A.; Hutzler, Stefan; Kreuz, Dorothea; Beissert, Tim; Bauer, Stefanie; Hubich-Rau, Stefanie; Tondera, Christiane; Eldin, Hosam Shams; Schmidt, Jörg; Vergara-Alert, Júlia; Süzer, Yasemin; Seifried, Janna; Hanschmann, Kay-Martin; Kalinke, Ulrich; Herold, Susanne; Sahin, Ugur; Cichutek, Klaus; Waibler, Zoe; Eickmann, Markus; Becker, Stephan

2015-01-01

ABSTRACT In 2012, the first cases of infection with the Middle East respiratory syndrome coronavirus (MERS-CoV) were identified. Since then, more than 1,000 cases of MERS-CoV infection have been confirmed; infection is typically associated with considerable morbidity and, in approximately 30% of cases, mortality. Currently, there is no protective vaccine available. Replication-competent recombinant measles virus (MV) expressing foreign antigens constitutes a promising tool to induce protective immunity against corresponding pathogens. Therefore, we generated MVs expressing the spike glycoprotein of MERS-CoV in its full-length (MERS-S) or a truncated, soluble variant of MERS-S (MERS-solS). The genes encoding MERS-S and MERS-solS were cloned into the vaccine strain MVvac2 genome, and the respective viruses were rescued (MVvac2-CoV-S and MVvac2-CoV-solS). These recombinant MVs were amplified and characterized at passages 3 and 10. The replication of MVvac2-CoV-S in Vero cells turned out to be comparable to that of the control virus MVvac2-GFP (encoding green fluorescent protein), while titers of MVvac2-CoV-solS were impaired approximately 3-fold. The genomic stability and expression of the inserted antigens were confirmed via sequencing of viral cDNA and immunoblot analysis. In vivo, immunization of type I interferon receptor-deficient (IFNAR−/−)-CD46Ge mice with 2 × 105 50% tissue culture infective doses of MVvac2-CoV-S(H) or MVvac2-CoV-solS(H) in a prime-boost regimen induced robust levels of both MV- and MERS-CoV-neutralizing antibodies. Additionally, induction of specific T cells was demonstrated by T cell proliferation, antigen-specific T cell cytotoxicity, and gamma interferon secretion after stimulation of splenocytes with MERS-CoV-S presented by murine dendritic cells. MERS-CoV challenge experiments indicated the protective capacity of these immune responses in vaccinated mice. IMPORTANCE Although MERS-CoV has not yet acquired extensive distribution

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

Infants with low vaccine antibody responses have altered innate cytokine response.

PubMed

Surendran, Naveen; Nicolosi, Ted; Pichichero, Michael

2016-11-11

We recently identified a population of 10% of infants who respond with sub-protective antibody levels to most routine primary pediatric vaccinations due to altered innate and adaptive immune responses. We term these infants as low vaccine responders (LVRs). Here we report new data showing that TLR7/8 agonist - R848 stimulation of PBMCs of LVR infants elicit significantly lower IFN-α, IL-12p70 and IL-1β, while inducing higher levels of CCL5 (RANTES) compared to normal vaccine responder (NVR) infants. Copyright © 2016 Elsevier Ltd. All rights reserved.

Vaccination of lambs against Taenia ovis infection using antigens collected during in vitro cultivation of larvae: passive protection via colostrum from vaccinated ewes and the duration of immunity from a single vaccination.

PubMed

Rickard, M D; Boddington, E B; McQuade, N

1977-11-01

Fifty Merino-cross ewes were vaccinated approximately four weeks before parturition with antigens collected during in vitro cultivation of Taenia ovis larvae. A further 50 pregnant ewes were sham-vaccinated at the same time. When the first 20 lambs from each group of ewes were one to two weeks old they were placed, with the ewes, on an experimental paddock heavily contaminated with T ovis eggs. After six weeks the lambs were killed and their total carcase musculature and hearts examined for cysticerci. The results showed that the ewes vaccinated in late pregnancy had conferred a very high degree of transcolostral immunity upon their lambs against the T ovis challenge infection. Eighty T ovis-free Merino-cross weaner lambs, four months old, were divided into two groups of 40. One group was vaccinated with T ovis culture antigens and the other group was sham-vaccinated. At intervals of one, four, eight and 12 months after vaccination 10 lambs from each group were allowed to graze on the plot contaminated with T ovis eggs. After six weeks the lambs were killed and examined for cysticerci of T ovis. The results indicated that the single vaccination had stimulated a high level of immunity which persisted for at least 12 months.

Influence of protein fold stability on immunogenicity and its implications for vaccine design

PubMed Central

Scheiblhofer, Sandra; Laimer, Josef; Machado, Yoan; Weiss, Richard; Thalhamer, Josef

2017-01-01

ABSTRACT Introduction: In modern vaccinology and immunotherapy, recombinant proteins more and more replace whole organisms to induce protective or curative immune responses. Structural stability of proteins is of crucial importance for efficient presentation of antigenic peptides on MHC, which plays a decisive role for triggering strong immune reactions. Areas covered: In this review, we discuss structural stability as a key factor for modulating the potency of recombinant vaccines and its importance for antigen proteolysis, presentation, and stimulation of B and T cells. Moreover, the impact of fold stability on downstream events determining the differentiation of T cells into effector cells is reviewed. We summarize studies investigating the impact of protein fold stability on the outcome of the immune response and provide an overview on computational methods to estimate the effects of point mutations on protein stability. Expert commentary: Based on this information, the rational design of up-to-date vaccines is discussed. A model for predicting immunogenicity of proteins based on their conformational stability at different pH values is proposed. PMID:28290225

Public trust in vaccination: an analytical framework.

PubMed

Gopichandran, Vijayaprasad

2017-01-01

While vaccination is one of the most successful public health interventions, there has always been a parallel movement against vaccines. Apart from scientific factors, the uptake of vaccinations is influenced by historical, political, sociocultural and economic factors. In India, the health system is struggling with logistical weaknesses in taking vaccination to the remotest corners; while on the other hand, some people in places where vaccination is available resist it. Unwillingness to be vaccinated is a growing problem in the developed world. This trend is gradually emerging in several parts of India as well. Other factors, such as heightened awareness of the profit motives of the vaccine industry, conflicts of interest among policy-makers, and social, cultural and religious considerations have eroded the people's trust in vaccination. This paper develops an analytical framework to assess trust in vaccination. The framework considers trust in vaccination from four perspectives - trust in the health system, the vaccine policy, vaccination providers and specific vaccines. The framework considers specific issues involved in vaccination trust, including the increasing scepticism towards medical technology, perceptions of conflicts of interest in the vaccine policy, and of lack of transparency and openness, the presence of strong alternative schools of thought, influence of the social media. The paper will conclude by arguing that engaging with communities and having a dialogue about the vaccination policy is an ethical imperative.

A Prototype Recombinant-Protein Based Chlamydia pecorum Vaccine Results in Reduced Chlamydial Burden and Less Clinical Disease in Free-Ranging Koalas (Phascolarctos cinereus).

PubMed

Waugh, Courtney; Khan, Shahneaz Ali; Carver, Scott; Hanger, Jonathan; Loader, Joanne; Polkinghorne, Adam; Beagley, Kenneth; Timms, Peter

2016-01-01

Diseases associated with Chlamydia pecorum infection are a major cause of decline in koala populations in Australia. While koalas in care can generally be treated, a vaccine is considered the only option to effectively reduce the threat of infection and disease at the population level. In the current study, we vaccinated 30 free-ranging koalas with a prototype Chlamydia pecorum vaccine consisting of a recombinant chlamydial MOMP adjuvanted with an immune stimulating complex. An additional cohort of 30 animals did not receive any vaccine and acted as comparison controls. Animals accepted into this study were either uninfected (Chlamydia PCR negative) at time of initial vaccination, or infected (C. pecorum positive) at either urogenital (UGT) and/or ocular sites (Oc), but with no clinical signs of chlamydial disease. All koalas were vaccinated/sampled and then re-released into their natural habitat before re-capturing and re-sampling at 6 and 12 months. All vaccinated koalas produced a strong immune response to the vaccine, as indicated by high titres of specific plasma antibodies. The incidence of new infections in vaccinated koalas over the 12-month period post-vaccination was slightly less than koalas in the control group, however, this was not statistically significant. Importantly though, the vaccine was able to significantly reduce the infectious load in animals that were Chlamydia positive at the time of vaccination. This effect was evident at both the Oc and UGT sites and was stronger at 6 months than at 12 months post-vaccination. Finally, the vaccine was also able to reduce the number of animals that progressed to disease during the 12-month period. While the sample sizes were small (statistically speaking), results were nonetheless striking. This study highlights the potential for successful development of a Chlamydia vaccine for koalas in a wild setting.

Vaccination of calves against Taenia saginata infection using antigens collected during in vitro cultivation of larvae: passive protection via colostrum from vaccinated cows and vaccination of calves protected by maternal antibody.

PubMed

Rickard, M D; Adolph, A J; Arundel, J H

1977-11-01

Six-to-11-day-old calves which received colostrum from cows vaccinated with in vitro culture antigens of Taenia saginata during their last month of pregnancy showed a high level of resistance to a challenge infection with T saginata eggs. Although colostral antibody reduced the numbers of larvae which became established it did not promote destruction of those which had undergone development. Calves which had received colostrum from vaccinated dams were themselves vaccinated with culture antigen when they were eight to 10 weeks old. These calves showed strong immunity to a challenge infection of T saginata eggs administered four weeks after vaccination.

Development of a multicomponent vaccine for Streptococcus pyogenes based on the antigenic targets of IVIG.

PubMed

Reglinski, Mark; Lynskey, Nicola N; Choi, Yoon Jung; Edwards, Robert J; Sriskandan, Shiranee

2016-04-01

Despite over a century of research and the careful scrutiny of many promising targets, there is currently no vaccine available for the prevention of Streptococcus pyogenes infection. Through analysis of the protective, anti-streptococcal components of pooled human immunoglobulin, we previously identified ten highly conserved and invariant S. pyogenes antigens that contribute to anti-streptococcal immunity in the adult population. We sought to emulate population immunity to S. pyogenes through a process of active vaccination, using the antigens targeted by pooled human immunoglobulin. Seven targets were produced recombinantly and mixed to form a multicomponent vaccine (Spy7). Vaccinated mice were challenged with S. pyogenes isolates representing four globally relevant serotypes (M1, M3, M12 and M89) using an established model of invasive disease. Vaccination with Spy7 stimulated the production of anti-streptococcal antibodies, and limited systemic dissemination of M1 and M3 S. pyogenes from an intramuscular infection focus. Vaccination additionally attenuated disease severity due to M1 S. pyogenes as evidenced by reduction in weight loss, and modulated cytokine release. Spy7 vaccination successfully stimulated the generation of protective anti-streptococcal immunity in vivo. Identification of reactive antigens using pooled human immunoglobulin may represent a novel route to vaccine discovery for extracellular bacteria. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Development of a multicomponent vaccine for Streptococcus pyogenes based on the antigenic targets of IVIG

PubMed Central

Reglinski, Mark; Lynskey, Nicola N.; Choi, Yoon Jung; Edwards, Robert J.; Sriskandan, Shiranee

2016-01-01

Summary Objectives Despite over a century of research and the careful scrutiny of many promising targets, there is currently no vaccine available for the prevention of Streptococcus pyogenes infection. Through analysis of the protective, anti-streptococcal components of pooled human immunoglobulin, we previously identified ten highly conserved and invariant S. pyogenes antigens that contribute to anti-streptococcal immunity in the adult population. We sought to emulate population immunity to S. pyogenes through a process of active vaccination, using the antigens targeted by pooled human immunoglobulin. Methods Seven targets were produced recombinantly and mixed to form a multicomponent vaccine (Spy7). Vaccinated mice were challenged with S. pyogenes isolates representing four globally relevant serotypes (M1, M3, M12 and M89) using an established model of invasive disease. Results Vaccination with Spy7 stimulated the production of anti-streptococcal antibodies, and limited systemic dissemination of M1 and M3 S. pyogenes from an intramuscular infection focus. Vaccination additionally attenuated disease severity due to M1 S. pyogenes as evidenced by reduction in weight loss, and modulated cytokine release. Conclusion Spy7 vaccination successfully stimulated the generation of protective anti-streptococcal immunity in vivo. Identification of reactive antigens using pooled human immunoglobulin may represent a novel route to vaccine discovery for extracellular bacteria. PMID:26880087

Experimental immunization of cats with a recombinant rabies-canine adenovirus vaccine elicits a long-lasting neutralizing antibody response against rabies.

PubMed

Hu, R L; Liu, Y; Zhang, S F; Zhang, F; Fooks, A R

2007-07-20

During the past decade, human rabies caused by cats has ranked the second highest in China. Several recombinant rabies vaccines have been developed for dogs. However, seldom have these vaccines been assessed or used in cats. In this trial, we report the experimental immunization of a recombinant canine adenovirus-rabies vaccine, CAV-2-E3Delta-RGP, in cats. Thirty cats were inoculated with the recombinant vaccine intramuscularly, orally and intranasally, respectively. Safety and efficacy studies were undertaken using the fluorescent antibody virus neutralization (FAVN) test and evaluated. Results showed that this recombinant vaccine is safe for cats as demonstrated by the three different routes of administration. The vaccine stimulated an efficient humoral response in the vaccinated cats when 10(8.5)PFU/ml of the recombinant vaccine was injected intramuscularly in a single dose. The neutralizing antibody level increased above 0.5IU/ml at 4 weeks after the vaccination. The mean antibody level ranged from 0.96+/-0.26 to 4.47+/-1.57IU/ml among individuals, and the antibody levels were elicited for at least 12 months. After this period, the immunized cats survived the challenge of CVS-24 and an obvious anemnestic and protective immune response was stimulated after the challenge. The immune response occurred later than the inactivated vaccine and the overall antibody level in the vaccinated cats was lower, but it was sufficient to confer protection of cats against infection. This demonstrated that a single, intramuscular dose of CAV-2-E3Delta-RGP stimulated a long-lasting protective immune response in cats and suggested that CAV-2-E3Delta-RGP could be considered as a potential rabies vaccine candidate for cats.

Dynamic high pressure induced strong and weak hydrogen bonds enhanced by pre-resonance stimulated Raman scattering in liquid water.

PubMed

Wang, Shenghan; Fang, Wenhui; Li, Fabing; Gong, Nan; Li, Zhanlong; Li, Zuowei; Sun, Chenglin; Men, Zhiwei

2017-12-11

355 nm pulsed laser is employed to excite pre-resonance forward stimulated Raman scattering (FSRS) of liquid water at ambient temperature. Due to the shockwave induced dynamic high pressure, the obtained Raman spectra begin to exhibit double peaks distribution at 3318 and 3373 cm -1 with the input energy of 17 mJ,which correspond with OH stretching vibration with strong and weak hydrogen (H) bonds. With laser energy rising from 17 to 27 mJ, the Stokes line at 3318 cm -1 shifts to 3255 and 3230 cm -1 because of the high pressure being enlarged. When the energy is up to 32 mJ, only 3373 cm -1 peak exists. The strong and weak H bond exhibit quite different energy dependent behaviors.

Current Trends in West Nile Virus Vaccine Development

PubMed Central

Amanna, Ian J.; Slifka, Mark K.

2014-01-01

West Nile virus (WNV) is a mosquito-borne flavivirus that has become endemic in the United States. From 1999-2012, there have been 37,088 reported cases of WNV and 1,549 deaths, resulting in a 4.2% case-fatality rate. Despite development of effective WNV vaccines for horses, there is no vaccine to prevent human WNV infection. Several vaccines have been tested in preclinical studies and to date there have been 8 clinical trials, with promising results in terms of safety and induction of antiviral immunity. Although mass vaccination is unlikely to be cost-effective, implementation of a targeted vaccine program may be feasible if a safe and effective vaccine can be brought to market. Further evaluation of new and advanced vaccine candidates is strongly encouraged. PMID:24689659

Willingness of reproductive-aged women in a Nigerian community to accept human papillomavirus vaccination for their children.

PubMed

Morhason-Bello, Imran O; Wallis, Selina; Adedokun, Babatunde O; Adewole, Isaac F

2015-10-01

The aim of this study was to determine the willingness of reproductive-aged women in a Nigerian community to allow human papillomavirus (HPV) vaccination in their children and the associated factors with this decision. A multistage household survey of 1002 women who participated in the HPV Vaccine and Cervical Cancer Prevention Survey from 26 August to 29 September 2012 at Ibadan North Local Government Area, Mokola Ibadan, Nigeria. Descriptive, bivariate and multivariable analyses were performed, and statistical significance was set at 95% confidence level (CI). There was high willingness (88.6%) to vaccinate, and this attitude was associated with previous history of genital discharge or sores (adjusted odds ratio, 1.91; 95%CI, 1.05-3.45), and knowledge that cervical cancer is preventable (adjusted odds ratio, 1.67; 95%CI, 1.07-2.59). On the likely acceptability of Nigerian HPV vaccine policy, about two-thirds strongly agreed to its incorporation into the routine immunization program (66.9%), it being free (66.7%) and mandatory (64.3%), amongst other factors. The commonest concerns raised were cost/expenses (10.2%), that it might encourage promiscuity (9.9%), or stimulate early sexual debut (6.7%), and fear of infertility (6.3%). This study found that the majority of Nigerian women are willing to vaccinate their children against HPV infection and would prefer free universal HPV vaccination with regulation to ensure better uptake. The concerns expressed would need to be addressed by policy-makers to increase its acceptability. © 2015 Japan Society of Obstetrics and Gynecology.

Ubiquitin-Fused and/or Multiple Early Genes from Cottontail Rabbit Papillomavirus as DNA Vaccines

PubMed Central

Leachman, Sancy A.; Shylankevich, Mark; Slade, Martin D.; Levine, Dana; K. Sundaram, Ranjini; Xiao, Wei; Bryan, Marianne; Zelterman, Daniel; Tiegelaar, Robert E.; Brandsma, Janet L.

2002-01-01

Human papillomavirus (HPV) vaccines have the potential to prevent cervical cancer by preventing HPV infection or treating premalignant disease. We previously showed that DNA vaccination with the cottontail rabbit papillomavirus (CRPV) E6 gene induced partial protection against CRPV challenge and that the vaccine's effects were greatly enhanced by priming with granulocyte-macrophage colony-stimulating factor (GM-CSF). In the present study, two additional strategies for augmenting the clinical efficacy of CRPV E6 vaccination were evaluated. The first was to fuse a ubiquitin monomer to the CRPV E6 protein to enhance antigen processing and presentation through the major histocompatibility complex class I pathway. Rabbits vaccinated with the wild-type E6 gene plus GM-CSF or with the ubiquitin-fused E6 gene formed significantly fewer papillomas than the controls. The papillomas also required a longer time to appear and grew more slowly. Finally, a significant proportion of the papillomas subsequently regressed. The ubiquitin-fused E6 vaccine was significantly more effective than the wild-type E6 vaccine plus GM-CSF priming. The second strategy was to vaccinate with multiple CRPV early genes to increase the breadth of the CRPV-specific response. DNA vaccines encoding the wild-type CRPV E1-E2, E6, or E7 protein were tested alone and in all possible combinations. All vaccines and combinations suppressed papilloma formation, slowed papilloma growth, and stimulated subsequent papilloma regression. Finally, the two strategies were merged and a combination DNA vaccine containing ubiquitin-fused versions of the CRPV E1, E2, and E7 genes was tested. This last vaccine prevented papilloma formation at all challenge sites in all rabbits, demonstrating complete protection. PMID:12097575

CD4+ T-cell responses to foot-and-mouth disease virus in vaccinated cattle.

PubMed

Carr, B Veronica; Lefevre, Eric A; Windsor, Miriam A; Inghese, Cristina; Gubbins, Simon; Prentice, Helen; Juleff, Nicholas D; Charleston, Bryan

2013-01-01

We have performed a series of studies to investigate the role of CD4(+) T-cells in the immune response to foot-and-mouth disease virus (FMDV) post-vaccination. Virus neutralizing antibody titres (VNT) in cattle vaccinated with killed FMD commercial vaccine were significantly reduced and class switching delayed as a consequence of rigorous in vivo CD4(+) T-cell depletion. Further studies were performed to examine whether the magnitude of T-cell proliferative responses correlated with the antibody responses. FMD vaccination was found to induce T-cell proliferative responses, with CD4(+) T-cells responding specifically to the FMDV antigen. In addition, gamma interferon (IFN-γ) was detected in the supernatant of FMDV antigen-stimulated PBMC and purified CD4(+) T-cells from vaccinated cattle. Similarly, intracellular IFN-γ could be detected specifically in purified CD4(+) T-cells after restimulation. It was not possible to correlate in vitro proliferative responses or IFN-γ production of PBMC with VNT, probably as a consequence of the induction of T-independent and T-dependent antibody responses and antigen non-specific T-cell responses. However, our studies demonstrate the importance of stimulating CD4(+) T-cell responses for the induction of optimum antibody responses to FMD-killed vaccines.

Relation between experimental and non-experimental study designs. HB vaccines: a case study

PubMed Central

Jefferson, T.; Demicheli, V.

1999-01-01

STUDY OBJECTIVE: To examine the relation between experimental and non- experimental study design in vaccinology. DESIGN: Assessment of each study design's capability of testing four aspects of vaccine performance, namely immunogenicity (the capacity to stimulate the immune system), duration of immunity conferred, incidence and seriousness of side effects, and number of infections prevented by vaccination. SETTING: Experimental and non-experimental studies on hepatitis B (HB) vaccines in the Cochrane Vaccines Field Database. RESULTS: Experimental and non-experimental vaccine study designs are frequently complementary but some aspects of vaccine quality can only be assessed by one of the types of study. More work needs to be done on the relation between study quality and its significance in terms of effect size.   PMID:10326054

Difference in immune response in vaccinated and unvaccinated Swedish individuals after the 2009 influenza pandemic

PubMed Central

2014-01-01

Background Previous exposures to flu and subsequent immune responses may impact on 2009/2010 pandemic flu vaccine responses and clinical symptoms upon infection with the 2009 pandemic H1N1 influenza strain. Qualitative and quantitative differences in humoral and cellular immune responses associated with the flu vaccination in 2009/2010 (pandemic H1N1 vaccine) and natural infection have not yet been described in detail. We designed a longitudinal study to examine influenza- (flu-) specific immune responses and the association between pre-existing flu responses, symptoms of influenza-like illness (ILI), impact of pandemic flu infection, and pandemic flu vaccination in a cohort of 2,040 individuals in Sweden in 2009–2010. Methods Cellular flu-specific immune responses were assessed by whole-blood antigen stimulation assay, and humoral responses by a single radial hemolysis test. Results Previous seasonal flu vaccination was associated with significantly lower flu-specific IFN-γ responses (using a whole-blood assay) at study entry. Pandemic flu vaccination induced long-lived T-cell responses (measured by IFN-γ production) to influenza A strains, influenza B strains, and the matrix (M1) antigen. In contrast, individuals with pandemic flu infection (PCR positive) exhibited increased flu-specific T-cell responses shortly after onset of ILI symptoms but the immune response decreased after the flu season (spring 2010). We identified non-pandemic-flu vaccinated participants without ILI symptoms who showed an IFN-γ production profile similar to pandemic-flu infected participants, suggesting exposure without experiencing clinical symptoms. Conclusions Strong and long-lived flu-M1 specific immune responses, defined by IFN-γ production, in individuals after vaccination suggest that M1-responses may contribute to protective cellular immune responses. Silent flu infections appeared to be frequent in 2009/2010. The pandemic flu vaccine induced qualitatively and quantitatively

Seasonal and 2009 H1N1 influenza vaccine uptake, predictors of vaccination and self-reported barriers to vaccination among secondary school teachers and staff

PubMed Central

Painter, Julia E; Sales, Jessica M; Morfaw, Christopher; Jones, LaDawna M; Murray, Dennis; Wingood, Gina M; DiClemente, Ralph J; Hughes, James M

2011-01-01

Objective Teachers, like healthcare workers, may be a strategic target for influenza immunization programs. Influenza vaccination is critical to protect both teachers and the students they come into contact with. This study assessed factors associated with seasonal and H1N1 influenza vaccine uptake among middle- and high-school teachers. Results Seventy-eight percent of teachers who planned to receive seasonal influenza vaccine and 36% of those who planned to receive H1N1 influenza vaccine at baseline reported that they did so. Seasonal vaccine uptake was significantly associated with perceived severity (odds ratio [OR] 1.57, p = 0.05) and self-efficacy (OR 4.46, p = 0.006). H1N1 vaccine uptake was associated with perceived barriers (OR 0.7, p = 0.014) and social norms (OR 1.39, p = 0.05). The number one reason for both seasonal and H1N1 influenza vaccine uptake was to avoid getting seasonal/H1N1 influenza disease. The number one reason for seasonal influenza vaccine refusal was a concern it would make them sick and for H1N1 influenza vaccine refusal was concern about vaccine side effects. Methods Participants were recruited from two counties in rural Georgia. Data were collected from surveys in September 2009 and May 2010. Multivariate logistic regression was used to assess the association between teachers' attitudes toward seasonal and H1N1 influenza vaccination and vaccine uptake. Conclusions There is a strong association between the intention to be vaccinated against influenza (seasonal or 2009 H1N1) and actual vaccination uptake. Understanding and addressing factors associated with teachers' influenza vaccine uptake may enhance future influenza immunization efforts. PMID:21263225

Assessment of humoral and cellular-mediated immune response in chickens treated with tilmicosin, florfenicol, or enrofloxacin at the time of Newcastle disease vaccination.

PubMed

Khalifeh, M S; Amawi, M M; Abu-Basha, E A; Yonis, I Bani

2009-10-01

The effect of tilmicosin, florfenicol, or enrofloxacin on humoral and cell-mediated immune response induced by Newcastle disease (ND) vaccination was evaluated in 20-wk-old specific-pathogen-free layer chickens. Humoral immunity was measured by detection of ND virus (NDV) antibody titer and anti-NDV IgG response using the hemagglutination inhibition (HI) test and ELISA, respectively, whereas cell-mediated immunity was evaluated by measurement of chicken interferon gamma (ChIFN-gamma) produced in splenocytes cell culture stimulated with concanavalin A, inactivated NDV antigen, or live attenuated La Sota strain using ELISA. Florfenicol hampered the ND antibody production measured by both HI and ELISA. Tilmicosin and enrofloxacin reduced the production of ND antibody in the first 3 wk after the last ND vaccination measured by HI test, which suggests that these antibiotics exert their effect mainly on the IgM isotype. The ND-vaccinated, but not treated group, showed an increase in ChIFN-gamma production after NDV antigen-specific stimulation above the nonstimulated cell culture, whereas this effect was masked in all the antibiotic-treated groups due to the stronger ChIFN-gamma production background value reported in the nonstimulated cell culture. In conclusion, our results showed, for the first time, that tilmicosin, florfenicol, or enrofloxacin reduced the humoral immune response and had beneficial effects on the cell-mediated immune response. In addition, we demonstrated that the combination of both inactivated and attenuated ND vaccine gave a strong immune response at both the humoral and cellular level.

Preliminary evaluation of a thermosensitive chitosan hydrogel for Echinococcus granulosus vaccine delivery.

PubMed

Umair, Saleh; Pernthaner, Anton; Deng, Qing; Gibson, Blake; Hook, Sarah; Heath, David

2017-03-15

The EG95 vaccine is effective in protecting grazing animals from infection with Echinococcus granulosus. Six male lambs were used in the study, two were each vaccinated subcutaneously with 50μg EG95/1mg Quil-A, two animals were each vaccinated with 50μg EG95/1mg Quil-A in 1% chitosan thermolabile gel subcutaneously, and two animals served as non-vaccinated controls. Two vaccinations were given at a 7 week interval. Two vaccinations induced a significantly higher antibody titre in the chitosan group compared with the Quil-A only group. The chitosan vaccine group also had a significantly higher antibody titre compared with a positive control sera from vaccinated and challenged sheep. Incorporating the EG95/Quil-A vaccine in a thermo-responsive chitosan sol-gel stimulated, after the second injection, a high level of antibody absorbance which remained high for at least one year. This response was significantly greater than the response to vaccine without the gel. Copyright © 2017 Elsevier B.V. All rights reserved.

MUC1-specific immune therapy generates a strong anti-tumor response in a MUC1-tolerant colon cancer model

PubMed Central

Mukherjee, P.; Pathangey, L.B.; Bradley, J.B.; Tinder, T.L.; Basu, G.D.; Akporiaye, E.T.; Gendler, S.J.

2007-01-01

A MUC1-based vaccine was used in a preclinical model of colon cancer. The trial was conducted in a MUC1-tolerant immune competent host injected with MC38 colon cancer cells expressing MUC1. The vaccine included: MHC class I-restricted MUC1 peptides, MHC class II-restricted pan helper peptide, unmethylated CpG oligodeoxynucleotide, and granulocyte macrophage-colony stimulating factor. Immunization was successful in breaking MUC1 self-tolerance, and in eliciting a robust anti-tumor response. The vaccine stimulated IFN-γ-producing CD4+ helper and CD8+ cytotoxic T cells against MUC1 and other undefined MC38 tumor antigens. In the prophylactic setting, immunization caused complete rejection of tumor cells, while in the therapeutic regimen, tumor burden was significantly reduced. PMID:17166639

Provider communication about HPV vaccination: A systematic review

PubMed Central

Gilkey, Melissa B.; McRee, Annie-Laurie

2016-01-01

abstract Background. Improving HPV vaccination coverage in the US will require healthcare providers to recommend the vaccine more effectively. To inform quality improvement efforts, we systematically reviewed studies of provider communication about HPV vaccination. Methods. We searched MEDLINE, CINAHL, EMBASE, and POPLINE in August 2015 to identify studies of provider communication about HPV vaccination. Results. We identified 101 qualitative and quantitative studies. Providers less often recommended HPV vaccine if they were uncomfortable discussing sex, perceived parents as hesitant, or believed patients to be low risk. Patients less often received recommendations if they were younger, male, or from racial/ethnic minorities. Despite parents' preference for unambiguous recommendations, providers often sent mixed messages by failing to endorse HPV vaccine strongly, differentiating it from other vaccines, and presenting it as an “optional” vaccine that could be delayed. Conclusion. Interventions are needed to help providers deliver effective recommendations in the complex communication environment surrounding HPV vaccination. PMID:26838681

A human dendritic cell-based in vitro model to assess Mycobacterium tuberculosis SO2 vaccine immunogenicity.

PubMed

Etna, Marilena P; Giacomini, Elena; Severa, Martina; Pardini, Manuela; Aguilo, Nacho; Martin, Carlos; Coccia, Eliana M

2014-01-01

Among the tuberculosis (TB) vaccine candidates, SO2 is the prototype of the first live-attenuated vaccine that recently entered into clinical trials. To investigate the capacity of SO2 to stimulate an appropriate immune response in vitro within a human immunological context, a comparative analysis of the effects promoted by SO2, the current Bacille Calmette-Guerin (BCG) vaccine and Mycobacterium tuberculosis (Mtb) was conducted in human primary dendritic cells (DC), which are critical modulators of vaccine-induced immunity. In particular, we found that SO2 promotes the expression of maturation markers similarly to BCG but at a lower extent than Mtb. Moreover, SO2-infected DC released higher levels of interleukin (IL)-23 than BCG-infected cells, which account for the expansion of interferon (IFN)-γ-producing T cells in an IL-12-independent manner. In the autologous mixed leukocyte reaction setting, the expansion of IL-17-producing T cells was also observed in response to SO2 infection. Interestingly, apoptosis and autophagic flux, events required for the antigen presentation within MHC class II complex, were not affected in DC infected with SO2, conversely to what observed upon Mtb stimulation. Collectively, our results indicate that SO2 represents a promising TB vaccine candidate, which displays an attenuated phenotype and promotes in DC a stronger capacity to stimulate the Th response than BCG vaccine. Interestingly, the data obtained by using the human DC-based experimental setting mirrored the results derived from studies in animal models, suggesting that this system could be used for an efficient and rapid down-selection of new TB vaccine candidates, contributing to achieve the "3Rs" objective.

Measuring vaccine acceptance among Canadian parents: A survey of the Canadian Immunization Research Network.

PubMed

Dubé, Eve; Gagnon, Dominique; Ouakki, Manale; Bettinger, Julie A; Witteman, Holly O; MacDonald, Shannon; Fisher, William; Saini, Vineet; Greyson, Devon

2018-01-25

Parental decision making about childhood vaccinations is complex and multidimensional. There is a perception that the number of parents having concerns regarding childhood vaccinations has been increasing in Canada. The aim of this study was to explore vaccine hesitancy among Canadian parents and to examine factors associated with a parent's intention to vaccinate his/her child. Informed by the Theory of Planned Behaviour (TPB) this study assesses potential associations between parents' knowledge, attitudes and beliefs toward vaccination and their intention to vaccinate their child in the future. A national sample of Canadian parents of children aged 24-59 months (N = 2013) was surveyed using an online survey methodology. Half of the surveyed parents strongly intended to have their child vaccinated in the future. Parents' information needs and searches as well as parents' trust in different institutions were associated with intention to vaccinate. Parents who reported having frequently looked for vaccine information, who considered that it was their role as parents to question vaccines, or who had previously experienced difficulty accessing vaccination services were less likely to strongly intend to vaccinate their child in the future. Parents who had a high level of trust in doctors and public health were most likely to strongly intend to vaccinate their child. Results of the multivariate analysis showed that positive attitudes (aOR = 8.0; 95% CI: 6.0, 10.4), higher perceived social support (aOR = 3.0; 95% CI: 2.3, 3.93), and higher perceived behavioural control (aOR = 1.8; 95% CI: 1.4, 2.43) were associated with parents' intention to vaccinate their child. Findings of this study suggest that trust-building interventions that promote pro-vaccine social norms and that address negative attitudes toward vaccination could enhance vaccine acceptance among Canadian parents. Copyright © 2017 Elsevier Ltd. All rights reserved.

Exploiting virus-like particles as innovative vaccines against emerging viral infections.

PubMed

Jeong, Hotcherl; Seong, Baik Lin

2017-03-01

Emerging viruses pose a major threat to humans and livestock with global public health and economic burdens. Vaccination remains an effective tool to reduce this threat, and yet, the conventional cell culture often fails to produce sufficient vaccine dose. As an alternative to cell-culture based vaccine, virus-like particles (VLPs) are considered as a highpriority vaccine strategy against emerging viruses. VLPs represent highly ordered repetitive structures via macromolecular assemblies of viral proteins. The particulate nature allows efficient uptake into antigen presenting cells stimulating both innate and adaptive immune responses towards enhanced vaccine efficacy. Increasing research activity and translation opportunity necessitate the advances in the design of VLPs and new bioprocessing modalities for efficient and cost-effective production. Herein, we describe major achievements and challenges in this endeavor, with respect to designing strategies to harnessing the immunogenic potential, production platforms, downstream processes, and some exemplary cases in developing VLP-based vaccines.

The success of microneedle-mediated vaccine delivery into skin

PubMed Central

Marshall, Sarah; Sahm, Laura J.; Moore, Anne C.

2016-01-01

ABSTRACT Microneedles (MNs) are designed to specifically target the outermost, skin barrier layer, the stratum corneum, creating transient pathways for minimally invasive transcutaneous delivery. It is reported that MNs can facilitate delivery without stimulating the pain receptors or damaging blood vessels that lie beneath, thus being perceived as painless and associated with reduced bleeding. This immunocompetence of the skin, coupled with its ease of access, makes this organ an attractive vaccination site. The purpose of this review was to collate primary scientific literature pertaining to MN-mediated in vivo vaccination programmes. A total of 62 original research articles are presented, compiling vaccination strategies in 6 different models (mouse, rat, guinea pig, rabbit, pig, macaque and human). Vaccines tested span a wide range of viral, bacterial and protozoan pathogens and includes 7 of the 13 vaccine-preventable diseases, as defined by the WHO. This review highlights the paucity of available clinical trial data. MN-delivered vaccines have demonstrated safety and immunogenicity in pre-clinical models and boast desirable attributes such as painless administration, thermostability, dose-sparing capacity and the potential for self-administration. These advantages should contribute to enhanced global vaccine access. PMID:27050528

Malaria vaccines: past, present and future.

PubMed

von Seidlein, Lorenz; Bejon, Philip

2013-12-01

The currently available malaria control tools have allowed malaria elimination in many regions but there remain many regions where malaria control has made little progress. A safe and protective malaria vaccine would be a huge asset for malaria control. Despite the many challenges, efforts continue to design and evaluate malaria vaccine candidates. These candidates target different stages in the life cycle of Plasmodia. The most advanced vaccine candidates target the pre-erythrocytic stages in the life cycle of the parasite and include RTS,S/AS01, which has progressed through clinical development to the stage that it may be licensed in 2015. Attenuated whole-parasite vaccine candidates are highly protective, but there are challenges to manufacture and to administration. Cellular immunity is targeted by the prime-boost approach. Priming vectors trigger only modest responses but these are focused on the recombinant antigen. Boosting vectors trigger strong but broad non-specific responses. The heterologous sequence produces strong immunological responses to the recombinant antigen. Candidates that target the blood stages of the parasite have to result in an immune response that is more effective than the response to an infection to abort or control the infection of merozoites and hence disease. Finally, the sexual stages of the parasite offer another target for vaccine development, which would prevent the transmission of malaria. Today it seems unlikely that any candidate targeting a single antigen will provide complete protection against an organism of the complexity of Plasmodium. A systematic search for vaccine targets and combinations of antigens may be a more promising approach.

Adaptive immune responses to booster vaccination against yellow fever virus are much reduced compared to those after primary vaccination.

PubMed

Kongsgaard, Michael; Bassi, Maria R; Rasmussen, Michael; Skjødt, Karsten; Thybo, Søren; Gabriel, Mette; Hansen, Morten Bagge; Christensen, Jan Pravsgaard; Thomsen, Allan Randrup; Buus, Soren; Stryhn, Anette

2017-04-06

Outbreaks of Yellow Fever occur regularly in endemic areas of Africa and South America frequently leading to mass vaccination campaigns straining the availability of the attenuated Yellow Fever vaccine, YF-17D. The WHO has recently decided to discontinue regular booster-vaccinations since a single vaccination is deemed to confer life-long immune protection. Here, we have examined humoral (neutralizing antibody) and cellular (CD8 and CD4 T cell) immune responses in primary and booster vaccinees (the latter spanning 8 to 36 years after primary vaccination). After primary vaccination, we observed strong cellular immune responses with T cell activation peaking ≈2 weeks and subsiding to background levels ≈ 4 weeks post-vaccination. The number of antigen-specific CD8+ T cells declined over the following years. In >90% of vaccinees, in vitro expandable T cells could still be detected >10 years post-vaccination. Although most vaccinees responded to a booster vaccination, both the humoral and cellular immune responses observed following booster vaccination were strikingly reduced compared to primary responses. This suggests that pre-existing immunity efficiently controls booster inoculums of YF-17D. In a situation with epidemic outbreaks, one could argue that a more efficient use of a limited supply of the vaccine would be to focus on primary vaccinations.

Pathogen-mimicking vaccine delivery system designed with a bioactive polymer (inulin acetate) for robust humoral and cellular immune responses.

PubMed

Kumar, Sunny; Kesharwani, Siddharth S; Kuppast, Bhimanna; Bakkari, Mohammed Ali; Tummala, Hemachand

2017-09-10

New and improved vaccines are needed against challenging diseases such as malaria, tuberculosis, Ebola, influenza, AIDS, and cancer. The majority of existing vaccine adjuvants lack the ability to significantly stimulate the cellular immune response, which is required to prevent the aforementioned diseases. This study designed a novel particulate based pathogen-mimicking vaccine delivery system (PMVDS) to target antigen-presenting-cells (APCs) such as dendritic cells. The uniqueness of PMVDS is that the polymer used to prepare the delivery system, Inulin Acetate (InAc), activates the innate immune system. InAc was synthesized from the plant polysaccharide, inulin. PMVDS provided improved and persistent antigen delivery to APCs as an efficient vaccine delivery system, and simultaneously, activated Toll-Like Receptor-4 (TLR-4) on APCs to release chemokine's/cytokines as an immune-adjuvant. Through this dual mechanism, PMVDS robustly stimulated both the humoral (>32 times of IgG1 levels vs alum) and the cell-mediated immune responses against the encapsulated antigen (ovalbumin) in mice. More importantly, PMVDS stimulated both cytotoxic T cells and natural killer cells of cell-mediated immunity to provide tumor (B16-ova-Melanoma) protection in around 40% of vaccinated mice and significantly delayed tumor progression in rest of the mice. PMVDS is a unique bio-active vaccine delivery technology with broader applications for vaccines against cancer and several intracellular pathogens, where both humoral and cellular immune responses are desired. Copyright © 2017 Elsevier B.V. All rights reserved.

A CpG-containing oligodeoxynucleotide as an efficient adjuvant counterbalancing the Th1/Th2 immune response in diphtheria-tetanus-pertussis vaccine.

PubMed

Sugai, Toshiyuki; Mori, Masaaki; Nakazawa, Masatoshi; Ichino, Motohide; Naruto, Takuya; Kobayashi, Naoki; Kobayashi, Yoshinori; Minami, Mutsuhiko; Yokota, Shumpei

2005-11-16

Adjuvants in vaccines are immune stimulants that play an important role in the induction of effective and appropriate immune responses to vaccine component(s). Diphtheria-tetanus-pertussis (DPT) vaccine contains not only aluminum hydrate (alum) to enhance the immune response to the vaccine ingredients, but also, both for that purpose and as a principal ingredient, pertussis toxin (PT). However, both adjuvants strongly promote T helper (Th) 2 type immune responses. Th1 and Th2 type immune responses are counterbalanced in vivo, and a Th2-prone immune response is not effective against intracellular infections but promotes IgE production, which is related to allergic disease. In this study, we used the CpG motif contained in oligodeoxynucleotide (CpG-ODN), which has an adjuvant effect and also induces the Th1 response, as an adjuvant to this vaccine, and we investigated its adjuvanticity and its potential to modulate immune responses to DPT vaccine. Administration of DPT vaccine with CpG-ODN (DPT-alum/ODN) to mice significantly reduced the total IgE levels and increased the anti-PT specific IgG2a titer in serum, in comparison with ordinary DPT vaccine (DPT-alum). Moreover, we investigated the antibody response to orally administrated ovalbumin (OVA) after vaccine administration. In the DPT-alum/ODN-administered group, the OVA specific IgE production in serum greatly decreased in comparison with that in the DPT-alum-administered group. These data indicate that CpG-ODN was not useful only as an efficient vaccine adjuvant but also shifted the immune responses substantially toward Th1 and modulated the Th1/Th2 immune response in DPT vaccine. These data suggested new applications of CpG-ODN as adjuvants in DPT vaccine.

Zika virus-like particle (VLP) based vaccine

PubMed Central

Boigard, Hélène; Alimova, Alexandra; Martin, George R.; Katz, Al; Gottlieb, Paul

2017-01-01

The newly emerged mosquito-borne Zika virus poses a major public challenge due to its ability to cause significant birth defects and neurological disorders. The impact of sexual transmission is unclear but raises further concerns about virus dissemination. No specific treatment or vaccine is currently available, thus the development of a safe and effective vaccine is paramount. Here we describe a novel strategy to assemble Zika virus-like particles (VLPs) by co-expressing the structural (CprME) and non-structural (NS2B/NS3) proteins, and demonstrate their effectiveness as vaccines. VLPs are produced in a suspension culture of mammalian cells and self-assembled into particles closely resembling Zika viruses as shown by electron microscopy studies. We tested various VLP vaccines and compared them to analogous compositions of an inactivated Zika virus (In-ZIKV) used as a reference. VLP immunizations elicited high titers of antibodies, as did the In-ZIKV controls. However, in mice the VLP vaccine stimulated significantly higher virus neutralizing antibody titers than comparable formulations of the In-ZIKV vaccine. The serum neutralizing activity elicited by the VLP vaccine was enhanced using a higher VLP dose and with the addition of an adjuvant, reaching neutralizing titers greater than those detected in the serum of a patient who recovered from a Zika infection in Brazil in 2015. Discrepancies in neutralization levels between the VLP vaccine and the In-ZIKV suggest that chemical inactivation has deleterious effects on neutralizing epitopes within the E protein. This along with the inability of a VLP vaccine to cause infection makes it a preferable candidate for vaccine development. PMID:28481898

Nicotine vaccines: Will smokers take a shot at quitting?

PubMed Central

Lerman, Caryn; Cappella, Joseph N.

2010-01-01

Introduction: A vaccine against nicotine may soon be available to smokers who want to quit. The vaccine stimulates the production of antibodies that bind to nicotine, thereby impeding nicotine from crossing the blood-brain barrier and exerting psychoactive effects. The primary purpose of this study was to evaluate intentions to try a nicotine vaccine if one were to become available among a nationally representative sample of smokers. The secondary purpose was to assess whether information about genetic susceptibility to nicotine addiction had an effect on smokers’ interest in receiving the vaccine. Methods: Four hundred and twenty-seven adults were randomized to read one of two versions of a short description about the vaccine. One version framed addiction as genetically influenced, while the other framed it as environmentally influenced. Smokers were then asked about their intentions to use a nicotine vaccine if one were to become available in the future. Results: Across both groups, 53% indicated that they would be likely or very likely to try the vaccine. Using multivariate linear regression, the strongest predictors of vaccination intention were having a favorable attitude toward a nicotine vaccine (β = .41) and having a favorable attitude toward vaccination in general (β = .22). There were no significant effects of the framing conditions on intention to receive the vaccine. Discussion: Intentions to try a nicotine vaccine as a cessation method are relatively high among smokers. If the vaccine becomes available, specific groups of smokers may be more interested than others; education and recruitment efforts could be targeted appropriately. PMID:20185516

The search for animal models for Lassa fever vaccine development

PubMed Central

Lukashevich, Igor S

2013-01-01

Lassa virus (LASV) is the most prevalent arenavirus in West Africa and is responsible for several hundred thousand infections and thousands of deaths annually. The sizeable disease burden, numerous imported cases of Lassa fever (LF) and the possibility that LASV can be used as an agent of biological warfare make a strong case for vaccine development. Currently there is no licensed LF vaccine and research and devlopment is hampered by the high cost of nonhuman primate animal models and by biocontainment requirements (BSL-4). In addition, a successful LF vaccine has to induce a strong cell-mediated cross-protective immunity against different LASV lineages. All of these challenges will be addressed in this review in the context of available and novel animal models recently described for evaluation of LF vaccine candidates. PMID:23256740

The search for animal models for Lassa fever vaccine development.

PubMed

Lukashevich, Igor S

2013-01-01

Lassa virus (LASV) is the most prevalent arenavirus in West Africa and is responsible for several hundred thousand infections and thousands of deaths annually. The sizeable disease burden, numerous imported cases of Lassa fever (LF) and the possibility that LASV can be used as an agent of biological warfare make a strong case for vaccine development. Currently there is no licensed LF vaccine and research and devlopment is hampered by the high cost of nonhuman primate animal models and by biocontainment requirements (BSL-4). In addition, a successful LF vaccine has to induce a strong cell-mediated cross-protective immunity against different LASV lineages. All of these challenges will be addressed in this review in the context of available and novel animal models recently described for evaluation of LF vaccine candidates.

Construction and Evaluation of Novel Rhesus Monkey Adenovirus Vaccine Vectors

DOE PAGES

Abbink, Peter; Maxfield, Lori F.; Ng'ang'a, David; ...

2014-11-19

Adenovirus vectors are widely used as vaccine candidates for a variety of pathogens, including HIV-1. To date, human and chimpanzee adenoviruses have been explored in detail as vaccine vectors. Furthermore, the phylogeny of human and chimpanzee adenoviruses is overlapping, and preexisting humoral and cellular immunity to both are exhibited in human populations worldwide. More distantly related adenoviruses may therefore offer advantages as vaccine vectors. We describe the primary isolation and vectorization of three novel adenoviruses from rhesus monkeys. The seroprevalence of these novel rhesus monkey adenovirus vectors was extremely low in sub-Saharan Africa human populations, and these vectors proved tomore » have immunogenicity comparable to that of human and chimpanzee adenovirus vaccine vectors in mice. These rhesus monkey adenoviruses phylogenetically clustered with the poorly described adenovirus species G and robustly stimulated innate immune responses. These novel adenoviruses represent a new class of candidate vaccine vectors.« less

Construction and Evaluation of Novel Rhesus Monkey Adenovirus Vaccine Vectors

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

Abbink, Peter; Maxfield, Lori F.; Ng'ang'a, David

Adenovirus vectors are widely used as vaccine candidates for a variety of pathogens, including HIV-1. To date, human and chimpanzee adenoviruses have been explored in detail as vaccine vectors. Furthermore, the phylogeny of human and chimpanzee adenoviruses is overlapping, and preexisting humoral and cellular immunity to both are exhibited in human populations worldwide. More distantly related adenoviruses may therefore offer advantages as vaccine vectors. We describe the primary isolation and vectorization of three novel adenoviruses from rhesus monkeys. The seroprevalence of these novel rhesus monkey adenovirus vectors was extremely low in sub-Saharan Africa human populations, and these vectors proved tomore » have immunogenicity comparable to that of human and chimpanzee adenovirus vaccine vectors in mice. These rhesus monkey adenoviruses phylogenetically clustered with the poorly described adenovirus species G and robustly stimulated innate immune responses. These novel adenoviruses represent a new class of candidate vaccine vectors.« less

Increased B and T Cell Responses in M. bovis Bacille Calmette-Guérin Vaccinated Pigs Co-Immunized with Plasmid DNA Encoding a Prototype Tuberculosis Antigen

PubMed Central

Bruffaerts, Nicolas; Pedersen, Lasse E.; Vandermeulen, Gaëlle; Préat, Véronique; Stockhofe-Zurwieden, Norbert; Huygen, Kris; Romano, Marta

2015-01-01

The only tuberculosis vaccine currently available, bacille Calmette-Guérin (BCG) is a poor inducer of CD8+ T cells, which are particularly important for the control of latent tuberculosis and protection against reactivation. As the induction of strong CD8+ T cell responses is a hallmark of DNA vaccines, a combination of BCG with plasmid DNA encoding a prototype TB antigen (Ag85A) was tested. As an alternative animal model, pigs were primed with BCG mixed with empty vector or codon-optimized pAg85A by the intradermal route and boosted with plasmid delivered by intramuscular electroporation. Control pigs received unformulated BCG. The BCG-pAg85A combination stimulated robust and sustained Ag85A specific antibody, lymphoproliferative, IL-6, IL-10 and IFN-γ responses. IgG1/IgG2 antibody isotype ratio reflected the Th1 helper type biased response. T lymphocyte responses against purified protein derivative of tuberculin (PPD) were induced in all (BCG) vaccinated animals, but responses were much stronger in BCG-pAg85A vaccinated pigs. Finally, Ag85A-specific IFN-γ producing CD8+ T cells were detected by intracellular cytokine staining and a synthetic peptide, spanning Ag85A131-150 and encompassing two regions with strong predicted SLA-1*0401/SLA-1*0801 binding affinity, was promiscuously recognized by 6/6 animals vaccinated with the BCG-pAg85A combination. Our study provides a proof of concept in a large mammalian species, for a new Th1 and CD8+ targeting tuberculosis vaccine, based on BCG-plasmid DNA co-administration. PMID:26172261

HPV knowledge, vaccine acceptance, and vaccine series completion among female entertainment and sex workers in Phnom Penh, Cambodia: the Young Women's Health Study

PubMed Central

Wadhera, Priya; Evans, Jennifer L; Stein, Ellen; Gandhi, Monica; Couture, Marie-Claude; Sansothy, Neth; Sichan, Keo; Maher, Lisa; Kaldor, John; Page, Kimberly

2015-01-01

Human papillomavirus (HPV) is a common sexually transmitted infection (STI) and the causative agent for cervical cancer, a frequently occurring malignant disease among women in developing countries. We assessed HPV awareness prior to the delivery of a brief information and education intervention, and HPV vaccine provision to female entertainment and sex workers (N=220). At baseline, only 23.6% of women had heard of HPV. Following the educational intervention, 90% answered all the HPV knowledge questions correctly. Of 192 participants attending the first quarterly cohort visit where vaccine was offered, 149 (78%) were eligible for vaccination; HIV-positive (n=32) and pregnant (n=11) women were excluded. Acceptance of vaccine among eligible women was universal, and 79.2% completed the three-dose vaccination series. Women who reported use of amphetamine type stimulants (ATS) had significantly and independently lower odds of vaccine completion (Adjusted OR 0.24; 95% CI 0.08, 0.69). New pregnancies also had an impact on vaccine completion: 5.4% (8/149 5.4%) who started the series had to stop due to new pregnancy. Results demonstrate the effectiveness of a simple education intervention designed to increase HPV knowledge and the feasibility of successful HPV vaccine in a population that is often difficult to engage in preventive health care. PMID:25505042

Immune response in pigs treated with therapeutic doses of enrofloxacin at the time of vaccination against Aujeszky's disease.

PubMed

Pomorska-Mól, Małgorzata; Czyżewska-Dors, Ewelina; Kwit, Krzysztof; Rachubik, Jarosław; Lipowski, Andrzej; Pejsak, Zygmunt

2015-06-01

The effect of treatment with enrofloxacin was studied on the postvaccinal immune response in pigs. Forty pigs were used (control not vaccinated (C), control vaccinated (CV), vaccinated, received enrofloxacin (ENRO)). From day -1 to day 3 pigs from ENRO group received enrofloxacin at the recommended dose. Pigs from ENRO and CV groups were vaccinated twice against Aujeszky's disease virus (ADV). There was a significant delay in the production of humoral response of enrofloxacin dosed pigs when compared with CV group. Moreover, in ENRO group the significant decrease in IFN-γ production and significantly lower values of stimulation index after ADV restimulation was noted, as compared with CV group. The secretion of IL-6, IL-10 and TNF-α by PBMC after recall stimulation was also affected in ENRO group. The results indicate that enrofloxacin, in addition to its antimicrobial properties, possess significant immunomodulatory effects and may alter the immune response to vaccines. Copyright © 2015 Elsevier Ltd. All rights reserved.

Serum elevation of B lymphocyte stimulator does not increase regulatory B cells in glioblastoma patients undergoing immunotherapy.

PubMed

Saraswathula, Anirudh; Reap, Elizabeth A; Choi, Bryan D; Schmittling, Robert J; Norberg, Pamela K; Sayour, Elias J; Herndon, James E; Healy, Patrick; Congdon, Kendra L; Archer, Gerald E; Sanchez-Perez, Luis; Sampson, John H

2016-02-01

Regulatory B cells that secrete IL-10 (IL-10(+) Bregs) represent a suppressive subset of the B cell compartment with prominent anti-inflammatory capacity, capable of suppressing cellular and humoral responses to cancer and vaccines. B lymphocyte stimulator (BLyS) is a key regulatory molecule in IL-10(+) Breg biology with tightly controlled serum levels. However, BLyS levels can be drastically altered upon chemotherapeutic intervention. We have previously shown that serum BLyS levels are elevated, and directly associated, with increased antigen-specific antibody titers in patients with glioblastoma (GBM) undergoing lymphodepletive temozolomide chemotherapy and vaccination. In this study, we examined corresponding IL-10(+) Breg responses within this patient population and demonstrate that the IL-10(+) Breg compartment remains constant before and after administration of the vaccine, despite elevated BLyS levels in circulation. IL-10(+) Breg frequencies were not associated with serum BLyS levels, and ex vivo stimulation with a physiologically relevant concentration of BLyS did not increase IL-10(+) Breg frequency. However, BLyS stimulation did increase the frequency of the overall B cell compartment and promoted B cell proliferation upon B cell receptor engagement. Therefore, using BLyS as an adjuvant with therapeutic peptide vaccination could promote humoral immunity with no increase in immunosuppressive IL-10(+) Bregs. These results have implications for modulating humoral responses in human peptide vaccine trials in patients with GBM.

Immune Response to Hepatitis B Vaccine in HIV-Infected Subjects Using Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) as a Vaccine Adjuvant: ACTG Study 5220

PubMed Central

Overton, ET; Kang, M; Peters, MG; Umbleja, T; Alston-Smith, BL; Bastow, B; Demarco-Shaw, D; Koziel, MJ; Mong-Kryspin, L; Sprenger, HL; Yu, JY; Aberg, JA

2010-01-01

HIV-infected persons are at risk for HBV co-infection which is associated with increased morbidity and mortality. Unfortunately, protective immunity following HBV vaccination in HIV-infected persons is poor. This randomized, phase II, open label study aimed to evaluate efficacy and safety of 40 mcg HBV vaccine with or without 250 mcg GM-CSF administered at day 0, weeks 4 and 12. HIV-infected individuals ≥18 years of age, CD4 count ≥200 cells/mm3, seronegative for HBV and HCV, and naïve to HBV vaccination were eligible. Primary endpoints were quantitative HBsAb titers and adverse events. The study enrolled 48 subjects. Median age and baseline CD4 were 41 years and 446 cells/mm3, 37 were on ART, and 26 subjects had undetectable VL. Vaccination was well tolerated. Seven subjects in the GM-CSF group reported transient Grade ≥2 signs/symptoms (six Grade 2, one Grade 3), mostly aches and nausea. GM-CSF had no significant effect on VL or CD4. Four weeks after vaccination, 26 subjects (59%) developed a protective antibody response (HBsAb ≥10mIU/mL; 52% in the GM-CSF arm and 65% in the control arm) without improved Ab titer in the GM-CSF versus control arm (median 11 mIU/mL vs. 92 mIU/mL, respectively). Response was more frequent in those with CD4 ≥350 cells/mm3 (64%) than with CD4 <350 cells/mm3 (50%), though not statistically significant. GM-CSF as an adjuvant did not improve the Ab titer or the development of protective immunity to HBV vaccination in those receiving an accelerated vaccine schedule. Given the common routes of transmission for HIV and HBV, additional HBV vaccine research is warranted. PMID:20600512

GLA-SE, a synthetic toll-like receptor 4 agonist, enhances T-cell responses to influenza vaccine in older adults.

PubMed

Behzad, Hayedeh; Huckriede, Anke L W; Haynes, Laura; Gentleman, Beth; Coyle, Krysta; Wilschut, Jan C; Kollmann, Tobias R; Reed, Steven G; McElhaney, Janet E

2012-02-01

The decline in influenza vaccine efficacy in older adults is associated with a limited ability of current split-virus vaccines (SVVs) to stimulate cytotoxic T lymphocyte (CTL) responses required for clinical protection against influenza. The Toll-like receptor 4 agonist glucopyranosyl lipid adjuvant-stable emulsion (GLA-SE) was combined with SVV to stimulate peripheral blood mononuclear cells (PBMCs) in vitro to determine the cytokine response in dendritic cell subsets. Stimulated PBMCs were then challenged with live influenza virus to mimic the response to natural infection following vaccination, using previously identified T-cell correlates of protection. GLA-SE significantly increased the proportion of myeloid dendritic cells that produced tumor necrosis factor α, interleukin 6, and interleukin 12. When combined with SVV to stimulate PBMCs in vitro, this effect of GLA-SE was shown to regulate a T-helper 1 cell response upon challenge with live influenza virus; interleukin 10 production was suppressed, thus significantly increasing the interferon γ to interleukin 10 ratio and the cytolytic (granzyme B) response to influenza virus challenge, both of which have been shown to correlate with protection against influenza in older adults. Our findings suggest that a novel adjuvant, GLA-SE, combined with standard SVV has the potential to significantly improve vaccine-mediated protection against influenza in older adults.

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.

Vaccine Adjuvants: from 1920 to 2015 and Beyond

PubMed Central

Di Pasquale, Alberta; Preiss, Scott; Tavares Da Silva, Fernanda; Garçon, Nathalie

2015-01-01

The concept of stimulating the body’s immune response is the basis underlying vaccination. Vaccines act by initiating the innate immune response and activating antigen presenting cells (APCs), thereby inducing a protective adaptive immune response to a pathogen antigen. Adjuvants are substances added to vaccines to enhance the immunogenicity of highly purified antigens that have insufficient immunostimulatory capabilities, and have been used in human vaccines for more than 90 years. While early adjuvants (aluminum, oil-in-water emulsions) were used empirically, rapidly increasing knowledge on how the immune system interacts with pathogens means that there is increased understanding of the role of adjuvants and how the formulation of modern vaccines can be better tailored towards the desired clinical benefit. Continuing safety evaluation of licensed vaccines containing adjuvants/adjuvant systems suggests that their individual benefit-risk profile remains favorable. Adjuvants contribute to the initiation of the innate immune response induced by antigens; exemplified by inflammatory responses at the injection site, with mostly localized and short-lived effects. Activated effectors (such as APCs) then move to draining lymph nodes where they direct the type, magnitude and quality of the adaptive immune response. Thus, the right match of antigens and adjuvants can potentiate downstream adaptive immune responses, enabling the development of new efficacious vaccines. Many infectious diseases of worldwide significance are not currently preventable by vaccination. Adjuvants are the most advanced new technology in the search for new vaccines against challenging pathogens and for vulnerable populations that respond poorly to traditional vaccines. PMID:26343190

Superior induction of T cell responses to conserved HIV-1 regions by electroporated alphavirus replicon DNA compared to that with conventional plasmid DNA vaccine.

PubMed

Knudsen, Maria L; Mbewe-Mvula, Alice; Rosario, Maximillian; Johansson, Daniel X; Kakoulidou, Maria; Bridgeman, Anne; Reyes-Sandoval, Arturo; Nicosia, Alfredo; Ljungberg, Karl; Hanke, Tomás; Liljeström, Peter

2012-04-01

Vaccination using "naked" DNA is a highly attractive strategy for induction of pathogen-specific immune responses; however, it has been only weakly immunogenic in humans. Previously, we constructed DNA-launched Semliki Forest virus replicons (DREP), which stimulate pattern recognition receptors and induce augmented immune responses. Also, in vivo electroporation was shown to enhance immune responses induced by conventional DNA vaccines. Here, we combine these two approaches and show that in vivo electroporation increases CD8(+) T cell responses induced by DREP and consequently decreases the DNA dose required to induce a response. The vaccines used in this study encode the multiclade HIV-1 T cell immunogen HIVconsv, which is currently being evaluated in clinical trials. Using intradermal delivery followed by electroporation, the DREP.HIVconsv DNA dose could be reduced to as low as 3.2 ng to elicit frequencies of HIV-1-specific CD8(+) T cells comparable to those induced by 1 μg of a conventional pTH.HIVconsv DNA vaccine, representing a 625-fold molar reduction in dose. Responses induced by both DREP.HIVconsv and pTH.HIVconsv were further increased by heterologous vaccine boosts employing modified vaccinia virus Ankara MVA.HIVconsv and attenuated chimpanzee adenovirus ChAdV63.HIVconsv. Using the same HIVconsv vaccines, the mouse observations were supported by an at least 20-fold-lower dose of DNA vaccine in rhesus macaques. These data point toward a strategy for overcoming the low immunogenicity of DNA vaccines in humans and strongly support further development of the DREP vaccine platform for clinical evaluation.

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.

Vaccination of rhesus macaques with a vif-deleted simian immunodeficiency virus proviral DNA vaccine

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

Sparger, Ellen E.; Dubie, Robert A.; Shacklett, Barbara L.

2008-05-10

Studies in non-human primates, with simian immunodeficiency virus (SIV) and simian/human immunodeficiency virus (SHIV) have demonstrated that live-attenuated viral vaccines are highly effective; however these vaccine viruses maintain a low level of pathogenicity. Lentivirus attenuation associated with deletion of the viral vif gene carries a significantly reduced risk for pathogenicity, while retaining the potential for virus replication of low magnitude in the host. This report describes a vif-deleted simian immunodeficiency virus (SIV)mac239 provirus that was tested as an attenuated proviral DNA vaccine by inoculation of female rhesus macaques. SIV-specific interferon-{gamma} enzyme-linked immunospot responses of low magnitude were observed after immunizationmore » with plasmid containing the vif-deleted SIV provirus. However, vaccinated animals displayed strong sustained virus-specific T cell proliferative responses and increasing antiviral antibody titers. These immune responses suggested either persistent vaccine plasmid expression or low level replication of vif-deleted SIV in the host. Immunized and unvaccinated macaques received a single high dose vaginal challenge with pathogenic SIVmac251. A transient suppression of challenge virus load and a greater median survival time was observed for vaccinated animals. However, virus loads for vaccinated and unvaccinated macaques were comparable by twenty weeks after challenge and overall survival curves for the two groups were not significantly different. Thus, a vif-deleted SIVmac239 proviral DNA vaccine is immunogenic and capable of inducing a transient suppression of pathogenic challenge virus, despite severe attenuation of the vaccine virus.« less

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.

Vaccine-Mediated Activation of Human TLR4 Is Affected by Modulation of Culture Conditions during Whole-Cell Pertussis Vaccine Preparation

PubMed Central

Hoonakker, Marieke E.; Verhagen, Lisa M.; Pupo, Elder; de Haan, Alex; Metz, Bernard; Hendriksen, Coenraad F. M.; Han, Wanda G. H.; Sloots, Arjen

2016-01-01

The potency of whole-cell pertussis (wP) vaccines is still determined by an intracerebral mouse protection test. To allow development of suitable in vitro alternatives to this test, insight into relevant parameters to monitor the consistency of vaccine quality is essential. To this end, a panel of experimental wP vaccines of varying quality was prepared by sulfate-mediated suppression of the BvgASR master virulence regulatory system of Bordetella pertussis during cultivation. This system regulates the transcription of a range of virulence proteins, many of which are considered important for the induction of effective host immunity. The protein compositions and in vivo potencies of the vaccines were BvgASR dependent, with the vaccine containing the highest amount of virulence proteins having the highest in vivo potency. Here, the capacities of these vaccines to stimulate human Toll-like receptors (hTLR) 2 and 4 and the role these receptors play in wP vaccine-mediated activation of antigen-presenting cells in vitro were studied. Prolonged BvgASR suppression was associated with a decreased capacity of vaccines to activate hTLR4. In contrast, no significant differences in hTLR2 activation were observed. Similarly, vaccine-induced activation of MonoMac-6 and monocyte-derived dendritic cells was strongest with the highest potency vaccine. Blocking of TLR2 and TLR4 showed that differences in antigen-presenting cell activation could be largely attributed to vaccine-dependent variation in hTLR4 signalling. Interestingly, this BvgASR-dependent decrease in hTLR4 activation coincided with a reduction in GlcN-modified lipopolysaccharides in these vaccines. Accordingly, expression of the lgmA-C genes, required for this glucosamine modification, was significantly reduced in bacteria exposed to sulfate. Together, these findings demonstrate that the BvgASR status of bacteria during wP vaccine preparation is critical for their hTLR4 activation capacity and suggest that including

Identification of Leishmania infantum chagasi proteins in urine of patients with visceral leishmaniasis: a promising antigen discovery approach of vaccine candidates.

PubMed

Kashino, S S; Abeijon, C; Qin, L; Kanunfre, K A; Kubrusly, F S; Silva, F O; Costa, D L; Campos, D; Costa, C H N; Raw, I; Campos-Neto, A

2012-07-01

Visceral leishmaniasis (VL) is a serious lethal parasitic disease caused by Leishmania donovani in Asia and by Leishmania infantum chagasi in southern Europe and South America. VL is endemic in 47 countries with an annual incidence estimated to be 500,000 cases. This high incidence is due in part to the lack of an efficacious vaccine. Here, we introduce an innovative approach to directly identify parasite vaccine candidate antigens that are abundantly produced in vivo in humans with VL. We combined RP-HPLC and mass spectrometry and categorized three L. infantum chagasi proteins, presumably produced in spleen, liver and bone marrow lesions and excreted in the patients' urine. Specifically, these proteins were the following: Li-isd1 (XP_001467866.1), Li-txn1 (XP_001466642.1) and Li-ntf2 (XP_001463738.1). Initial vaccine validation studies were performed with the rLi-ntf2 protein produced in Escherichia coli mixed with the adjuvant BpMPLA-SE. This formulation stimulated potent Th1 response in BALB/c mice. Compared to control animals, mice immunized with Li-ntf2+ BpMPLA-SE had a marked parasite burden reduction in spleens at 40 days post-challenge with virulent L. infantum chagasi. These results strongly support the proposed antigen discovery strategy of vaccine candidates to VL and opens novel possibilities for vaccine development to other serious infectious diseases. © 2012 Blackwell Publishing Ltd.

Controlled and targeted release of antigens by intelligent shell for improving applicability of oral vaccines.

PubMed

Zhang, Lei; Zeng, Zhanzhuang; Hu, Chaohua; Bellis, Susan L; Yang, Wendi; Su, Yintao; Zhang, Xinyan; Wu, Yunkun

2016-01-01

Conventional oral vaccines with simple architecture face barriers with regard to stimulating effective immunity. Here we describe oral vaccines with an intelligent phase-transitional shielding layer, poly[(methyl methacrylate)-co-(methyl acrylate)-co-(methacrylic acid)]-poly(D,L-lactide-co-glycolide) (PMMMA-PLGA), which can protect antigens in the gastro-intestinal tract and achieve targeted vaccination in the large intestine. With the surface immunogenic protein (SIP) from group B Streptococcus (GBS) entrapped as the antigen, oral administration with PMMMA-PLGA (PTRBL)/Trx-SIP nanoparticles stimulated robust immunity in tilapia, an animal with a relatively simple immune system. The vaccine succeeded in protecting against Streptococcus agalactiae, a pathogen of worldwide importance that threatens human health and is transmitted in water with infected fish. After oral vaccination with PTRBL/Trx-SIP, tilapia produced enhanced levels of SIP specific antibodies and displayed durability of immune protection. 100% of the vaccinated tilapia were protected from GBS infection, whereas the control groups without vaccines or vaccinated with Trx-SIP only exhibited respective infection rates of 100% or >60% within the initial 5 months after primary vaccination. Experiments in vivo demonstrated that the recombinant antigen Trx-SIP labeled with FITC was localized in colon, spleen and kidney, which are critical sites for mounting an immune response. Our results revealed that, rather than the size of the nanoparticles, it is more likely that the negative charge repulsion produced by ionization of the carboxyl groups in PMMMA shielded the nanoparticles from uptake by small intestinal epithelial cells. This system resolves challenges arising from gastrointestinal damage to antigens, and more importantly, offers a new approach applicable for oral vaccination. Copyright © 2015 Elsevier Ltd. All rights reserved.

A randomized controlled study on the efficacy of a novel combination vaccine against enzootic pneumonia (Mycoplasma hyopneumoniae) and porcine Circovirus type 2 (PCV2) in the presence of strong maternally derived PCV2 immunity in pigs.

PubMed

Tassis, Panagiotis D; Tsakmakidis, Ioannis; Papatsiros, Vassileios G; Koulialis, Dimitrios; Nell, Tom; Brellou, Georgia; Tzika, Eleni D

2017-04-07

Mycoplasma hyopneumoniae (M. hyo) and Porcine Circovirus Type 2 (PCV2) are major pathogens that cause significant health problems in swine worldwide. Maternal derived immunity (MDI) has been suggested as a significant immediate defence factor for newborn piglets and may interfere with piglet's vaccination-induced immunity. The study aimed to assess the efficacy of a novel combination vaccine (consisting of PCV2 subunits and inactivated M. hyo strain J), against PCV2 and M. hyo natural infection [Porcilis ® PCV M Hyo (MSD Animal Health, Boxmeer, the Netherlands)], in the presence of strong maternally derived PCV2 immunity (antibody titre averaged 11.08 log 2 ), under field conditions. The study was performed according to a controlled, randomized and blinded design in a Greek swine unit with Enzootic Pneumonia (EP) and subclinical PCV2 infection. In total, 600 healthy three-week-old suckling piglets were allocated randomly, either to treatment (vaccinated with the test product) or control group (injected with sterile buffered saline). Vaccination significantly reduced the severity of lung lesions at slaughter (lesions of cranio-ventral pulmonary consolidation) (P < 0.001). The overall mean lung lesion score (LLS) was 9.6 in the vaccinated group and 12.2 in controls. The level of PCV2 viraemia was significantly reduced in vaccinated pigs. Furthermore, 25 g higher average daily weight gain (ADWG) was observed during the finishing phase (P < 0.001) and 18 g greater ADWG overall (P < 0.001). Results of LLS, PCV2 viremia and ADWG support the test product's efficacy in the face of strong maternally derived PCV2 immunity.

The immunology of smallpox vaccines

PubMed Central

Kennedy, Richard B; Ovsyannikova, Inna G; Jacobson, Robert M; Poland, Gregory A

2010-01-01

In spite of the eradication of smallpox over 30 years ago; orthopox viruses such as smallpox and monkeypox remain serious public health threats both through the possibility of bioterrorism and the intentional release of smallpox and through natural outbreaks of emerging infectious diseases such as monkeypox. The eradication effort was largely made possible by the availability of an effective vaccine based on the immunologically cross-protective vaccinia virus. Although the concept of vaccination dates back to the late 1800s with Edward Jenner, it is only in the past decade that modern immunologic tools have been applied toward deciphering poxvirus immunity. Smallpox vaccines containing vaccinia virus elicit strong humoral and cellular immune responses that confer cross-protective immunity against variola virus for decades after immunization. Recent studies have focused on: establishing the longevity of poxvirus-specific immunity, defining key immune epitopes targeted by T and B cells, developing subunit-based vaccines, and developing genotypic and phenotypic immune response profiles that predict either vaccine response or adverse events following immunization. PMID:19524427

Exosomal pMHC-I complex targets T cell-based vaccine to directly stimulate CTL responses leading to antitumor immunity in transgenic FVBneuN and HLA-A2/HER2 mice and eradicating trastuzumab-resistant tumor in athymic nude mice.

PubMed

Wang, Lu; Xie, Yufeng; Ahmed, Khawaja Ashfaque; Ahmed, Shahid; Sami, Amer; Chibbar, Rajni; Xu, Qingyong; Kane, Susan E; Hao, Siguo; Mulligan, Sean J; Xiang, Jim

2013-07-01

One of the major obstacles in human epidermal growth factor receptor 2 (HER2)-specific trastuzumab antibody immunotherapy of HER2-positive breast cancer is the development of trastuzumab resistance, warranting the search for other therapeutic strategies. Using mouse models, we previously demonstrated that ovalbumin (OVA)-specific dendritic cell (DC)-released exosome (EXOOVA)-targeted CD4(+) T cell-based (OVA-TEXO) vaccine stimulates efficient cytotoxic T lymphocyte (CTL) responses via exosomal peptide/major histocompatibility complex (pMHC)-I, exosomal CD80 and endogenous IL-2 signaling; and long-term CTL memory by means of via endogenous CD40L signaling. In this study, using two-photon microscopy, we provide the first visual evidence on targeting OVA-TEXO to cognate CD8(+) T cells in vivo via exosomal pMHC-I complex. We prepared HER2/neu-specific Neu-TEXO and HER2-TEXO vaccines using adenoviral vector (AdVneu and AdVHER2)-transfected DC (DCneu and DCHER2)-released EXOs (EXOneu and EXOHER2), and assessed their stimulatory effects on HER2/neu-specific CTL responses and antitumor immunity. We demonstrate that Neu-TEXO vaccine is capable of stimulating efficient neu-specific CTL responses, leading to protective immunity against neu-expressing Tg1-1 breast cancer in all 6/6 transgenic (Tg) FVBneuN mice with neu-specific self-immune tolerance. We also demonstrate that HER2-TEXO vaccine is capable of inducing HER2-specific CTL responses and protective immunity against transgene HLA-A2(+)HER2(+) BL6-10A2/HER2 B16 melanoma in 2/8 double Tg HLA-A2/HER2 mice with HER2-specific self-immune tolerance. The remaining 6/8 mice had significantly prolonged survival. Furthermore, we demonstrate that HER2-TEXO vaccine stimulates responses of CD8(+) T cells capable of not only inducing killing activity to HLA-A2(+)HER2(+) BL6-10A2/HER2 melanoma and trastuzumab-resistant BT474A2 breast cancer cells in vitro but also eradicating 6-day palpable HER2(+) BT474A2 breast cancer (3-4 mm in

Safety and immunogenicity of typhoid fever and yellow fever vaccines when administered concomitantly with quadrivalent meningococcal ACWY glycoconjugate vaccine in healthy adults.

PubMed

Alberer, Martin; Burchard, Gerd; Jelinek, Tomas; Reisinger, Emil; Beran, Jiri; Hlavata, Lucie Cerna; Forleo-Neto, Eduardo; Dagnew, Alemnew F; Arora, Ashwani K

2015-01-01

Compact and short pre-travel immunization schedules, which include several vaccinations in a single visit, are desirable for many travelers. However, concomitant vaccination could potentially compromise immunogenicity and/or safety of the individual vaccines and, therefore, possible vaccine interferences should be carefully assessed. This article discusses the immunogenicity and safety of travel vaccines for typhoid fever (TF) and yellow fever (YF), when administered with or without a quadrivalent meningococcal glycoconjugate ACWY-CRM vaccine (MenACWY-CRM). Healthy adults (18-≤60 years) were randomized to one of three vaccine regimens: TF + YF + MenACWY-CRM (group I; n = 100), TF + YF (group II; n = 101), or MenACWY-CRM (group III; n = 100). Immunogenicity at baseline and 4 weeks post-vaccination (day 29) was assessed by serum bactericidal assay using human complement (hSBA), enzyme-linked immunosorbent assay (ELISA), or a neutralization test. Adverse events (AEs) and serious adverse events (SAEs) were collected throughout the study period. Non-inferiority of post-vaccination geometric mean concentrations (GMCs) and geometric mean titers (GMTs) was established for TF and YF vaccines, respectively, when given concomitantly with MenACWY-CRM vaccine versus when given alone. The percentages of subjects with seroprotective neutralizing titers against YF on day 29 were similar in groups I and II. The antibody responses to meningococcal serogroups A, C, W-135, and Y were within the same range when MenACWY-CRM was given separately or together with TF and YF vaccines. The percentage of subjects reporting AEs was the same for TF and YF vaccines with or without MenACWY-CRM vaccine. There were no reports of SAEs or AEs leading to study withdrawals. These data provide evidence that MenACWY-CRM can be administered with typhoid Vi polysaccharide vaccine and live attenuated YF vaccine without compromising antibody responses stimulated by the

Achieving high coverage in Rwanda's national human papillomavirus vaccination programme.

PubMed

Binagwaho, Agnes; Wagner, Claire M; Gatera, Maurice; Karema, Corine; Nutt, Cameron T; Ngabo, Fidele

2012-08-01

Virtually all women who have cervical cancer are infected with the human papillomavirus (HPV). Of the 275,000 women who die from cervical cancer every year, 88% live in developing countries. Two vaccines against the HPV have been approved. However, vaccine implementation in low-income countries tends to lag behind implementation in high-income countries by 15 to 20 years. In 2011, Rwanda's Ministry of Health partnered with Merck to offer the Gardasil HPV vaccine to all girls of appropriate age. The Ministry formed a "public-private community partnership" to ensure effective and equitable delivery. Thanks to a strong national focus on health systems strengthening, more than 90% of all Rwandan infants aged 12-23 months receive all basic immunizations recommended by the World Health Organization. In 2011, Rwanda's HPV vaccination programme achieved 93.23% coverage after the first three-dose course of vaccination among girls in grade six. This was made possible through school-based vaccination and community involvement in identifying girls absent from or not enrolled in school. A nationwide sensitization campaign preceded delivery of the first dose. Through a series of innovative partnerships, Rwanda reduced the historical two-decade gap in vaccine introduction between high- and low-income countries to just five years. High coverage rates were achieved due to a delivery strategy that built on Rwanda's strong vaccination system and human resources framework. Following the GAVI Alliance's decision to begin financing HPV vaccination, Rwanda's example should motivate other countries to explore universal HPV vaccine coverage, although implementation must be tailored to the local context.

Peer pressure is a double-edged sword in vaccination dynamics

NASA Astrophysics Data System (ADS)

Wu, Zhi-Xi; Zhang, Hai-Feng

2013-10-01

Whether or not to change behavior depends not only on the personal success of each individual, but also on the success and/or behavior of others. Using this as motivation, we incorporate the impact of peer pressure into a susceptible-vaccinated-infected-recovered (SVIR) epidemiological model, where the propensity to adopt a particular vaccination strategy depends both on individual success as well as on the strategies of neighbors. We show that plugging into the peer pressure is a double-edged sword, which, on the one hand, strongly promotes vaccination when its cost is below a critical value, but, on the other hand, it can also strongly impede it if the critical value is exceeded. We explain this by revealing a facilitated cluster formation process that is induced by the peer pressure. Due to this, the vaccinated individuals are inclined to cluster together and therefore become unable to efficiently inhibit the spread of the infectious disease if the vaccination is costly. If vaccination is cheap, however, they reinforce each other in using it. Our results are robust to variations of the SVIR dynamics on different population structures.

Polysaccharide vaccines for preventing serogroup A meningococcal meningitis.

PubMed

Patel, M; Lee, C K

2001-01-01

Controlled trials over two decades ago showed that the polysaccharide vaccine prevented serogroup A meningococcal meningitis. Subsequent non-experimental studies suggested age-specific variations in the duration of protection among young children. To determine the effect of polysaccharide serogroup A vaccine for preventing serogroup A meningococcal meningitis. MEDLINE and the Cochrane Controlled Trials Register. The first stage of the review included prospective controlled trials. The second stage included non-experimental studies that addressed questions unanswered by the trials, i.e. the duration of protection and the effect of a booster dose in children under 2 years of age. One reviewer assessed the methodological quality of the trials, and two reviewers independently identified and assessed the non-experimental studies. Data from the trials were pooled using the Exact method to assess vaccine efficacy at 1, 2 and 3 years post- vaccination. The protective effect within the first year was consistent across all 8 trials, vaccine efficacy was 95% (Exact 95% CI 87%, 99%). Protection extended into the second and third year after vaccination, but the results did not attain statistical significance. The only trial that assessed the effect of a booster dose in children less than 18 months old, lacked adequate statistical power. In the three other trials that included children less than 6 years old (one in Sudan and two in Nigeria), none of the vaccinated children developed meningitis, but the results did not attain statistical significance. Data from the two non-experimental studies included in this review were not pooled with the trial data because of methodological limitations. For the first year after vaccination, the vaccine was strongly protective in participants over 5 years of age. It was also protective beyond the first year after vaccination, but the level of vaccine efficacy could not be determined with precision. Children aged 1 to 5 years in developing

Single-cycle adenovirus vectors in the current vaccine landscape.

PubMed

Barry, Michael

2018-02-01

Traditional inactivated and protein vaccines generate strong antibodies, but struggle to generate T cell responses. Attenuated pathogen vaccines generate both, but risk causing the disease they aim to prevent. Newer gene-based vaccines drive both responses and avoid the risk of infection. While these replication-defective (RD) vaccines work well in small animals, they can be weak in humans because they do not replicate antigen genes like more potent replication-competent (RC) vaccines. RC vaccines generate substantially stronger immune responses, but also risk causing their own infections. To circumvent these problems, we developed single-cycle adenovirus (SC-Ad) vectors that amplify vaccine genes, but that avoid the risk of infection. This review will discuss these vectors and their prospects for use as vaccines. Areas covered: This review provides a background of different types of vaccines. The benefits of gene-based vaccines and their ability to replicate antigen genes are described. Adenovirus vectors are discussed and compared to other vaccine types. Replication-defective, single-cycle, and replication-competent Ad vaccines are compared. Expert commentary: The potential utility of these vaccines are discussed when used against infectious diseases and as cancer vaccines. We propose a move away from replication-defective vaccines towards more robust replication-competent or single-cycle vaccines.

Virus like particle-based vaccines against emerging infectious disease viruses.

PubMed

Liu, Jinliang; Dai, Shiyu; Wang, Manli; Hu, Zhihong; Wang, Hualin; Deng, Fei

2016-08-01

Emerging infectious diseases are major threats to human health. Most severe viral disease outbreaks occur in developing regions where health conditions are poor. With increased international travel and business, the possibility of eventually transmitting infectious viruses between different countries is increasing. The most effective approach in preventing viral diseases is vaccination. However, vaccines are not currently available for numerous viral diseases. Virus-like particles (VLPs) are engineered vaccine candidates that have been studied for decades. VLPs are constructed by viral protein expression in various expression systems that promote the selfassembly of proteins into structures resembling virus particles. VLPs have antigenicity similar to that of the native virus, but are non-infectious as they lack key viral genetic material. VLP vaccines have attracted considerable research interest because they offer several advantages over traditional vaccines. Studies have shown that VLP vaccines can stimulate both humoral and cellular immune responses, which may offer effective antiviral protection. Here we review recent developments with VLP-based vaccines for several highly virulent emerging or re-emerging infectious diseases. The infectious agents discussed include RNA viruses from different virus families, such as the Arenaviridae, Bunyaviridae, Caliciviridae, Coronaviridae, Filoviridae, Flaviviridae, Orthomyxoviridae, Paramyxoviridae, and Togaviridae families.

Effective and lesion-free cutaneous influenza vaccination

PubMed Central

Wang, Ji; Li, Bo; Wu, Mei X.

2015-01-01

The current study details efficient lesion-free cutaneous vaccination via vaccine delivery into an array of micropores in the skin, instead of bolus injection at a single site. Such delivery effectively segregated vaccine-induced inflammation, resulting in rapid resolution of the inflammation, provided that distances between any two micropores were sufficient. When the inoculation site was treated by FDA-approved nonablative fractional laser (NAFL) before insertion of a PR8 model influenza vaccine-packaged, biodegradable microneedle array (MNs), mice displayed vigorous antigen-uptake, eliciting strong Th1-biased immunity. These animals were completely protected from homologous viral challenges, and fully or partially protected from heterologous H1N1 and H3N2 viral challenges, whereas mice receiving MNs alone suffered from severe illnesses or died of similar viral challenges. NAFL-mediated adjuvanicity was ascribed primarily to dsDNA and other “danger” signals released from laser-damaged skin cells. Thus, mice deficient in dsDNA-sensing pathway, but not Toll like receptor (TLR) or inflammasome pathways, showed poor responses to NAFL. Importantly, with this novel approach both mice and swine exhibited strong protective immunity without incurring any appreciable skin irritation, in sharp contrast to the overt skin irritation caused by intradermal injections. The effective lesion-free cutaneous vaccination merits further clinical studies. PMID:25848020

Development of an acid-resistant Salmonella Typhi Ty21a attenuated vector for improved oral vaccine delivery

USDA-ARS?s Scientific Manuscript database

The licensed oral, live-attenuated bacterial vaccine for typhoid fever, Salmonella Typhi strain Ty21a, has also been utilized as a vaccine delivery platform for expression of diverse foreign antigens that stimulate protection against shigellosis, anthrax, plague, or human papilloma virus. However, T...

Coadministration of the Campylobacter jejuni N-Glycan-Based Vaccine with Probiotics Improves Vaccine Performance in Broiler Chickens

PubMed Central

Perez-Muñoz, M. E.; Gouveia, G. J.; Wanford, J. J.; Lango-Scholey, L.; Panagos, C. G.; Srithayakumar, V.; Plastow, G. S.; Coros, C.; Bayliss, C. D.; Edison, A. S.; Walter, J.

2017-01-01

ABSTRACT Source attribution studies report that the consumption of contaminated poultry is the primary source for acquiring human campylobacteriosis. Oral administration of an engineered Escherichia coli strain expressing the Campylobacter jejuni N-glycan reduces bacterial colonization in specific-pathogen-free leghorn chickens, but only a fraction of birds respond to vaccination. Optimization of the vaccine for commercial broiler chickens has great potential to prevent the entry of the pathogen into the food chain. Here, we tested the same vaccination approach in broiler chickens and observed similar efficacies in pathogen load reduction, stimulation of the host IgY response, the lack of C. jejuni resistance development, uniformity in microbial gut composition, and the bimodal response to treatment. Gut microbiota analysis of leghorn and broiler vaccine responders identified one member of Clostridiales cluster XIVa, Anaerosporobacter mobilis, that was significantly more abundant in responder birds. In broiler chickens, coadministration of the live vaccine with A. mobilis or Lactobacillus reuteri, a commonly used probiotic, resulted in increased vaccine efficacy, antibody responses, and weight gain. To investigate whether the responder-nonresponder effect was due to the selection of a C. jejuni “supercolonizer mutant” with altered phase-variable genes, we analyzed all poly(G)-containing loci of the input strain compared to nonresponder colony isolates and found no evidence of phase state selection. However, untargeted nuclear magnetic resonance (NMR)-based metabolomics identified a potential biomarker negatively correlated with C. jejuni colonization levels that is possibly linked to increased microbial diversity in this subgroup. The comprehensive methods used to examine the bimodality of the vaccine response provide several opportunities to improve the C. jejuni vaccine and the efficacy of any vaccination strategy. IMPORTANCE Campylobacter jejuni is a common

Correlates of protection, antigen delivery and molecular epidemiology: basics for designing an HIV vaccine.

PubMed

Wagner, R; Shao, Y; Wolf, H

1999-03-26

Major obstacles in the development of HIV vaccines are the high variability of the virus and its complex interaction with the immune system. Recent studies demonstrated, that CTLs recognizing highly conserved epitopes in the group-specific antigen are capable of controlling HIV-replication in long-term nonprogressors. Necessary consequences for novel vaccine concepts are the presentation of a large repertoire of antigenic sites as well as the stimulation of different effectors of the immune system. Accordingly, different types of recombinant HIV-1 virus-like particles (VLPs) have been constructed stimulating the induction of neutralizing antibodies and HIV-specific CD8-positive CTL responses in preclinical studies. With respect to future vaccine trials, HIV vaccine formulations may need to be tailored to the local strains circulating within a geographical region. The expert group of the joint United Nations Programme on AIDS recently identified Yunnan, a southwestern province of China, as a region, in which the HIV epidemic is starting to gain speed, resembling to the situation in Thailand 10 years ago. A molecular clone of a representative virus strain is now available for the development of innovative antigen delivery systems aiming to be evaluated in future clinical vaccine trials throughout this area.

An update on the use of laser technology in skin vaccination

PubMed Central

Chen, Xinyuan; Wang, Ji; Shah, Dilip; Wu, Mei X

2014-01-01

Vaccination via skin often induces stronger immune responses than via muscle. This, in line with potential needle-free, painless delivery, makes skin a very attractive site for immunization. Yet, despite decades of effort, effective skin delivery is still in its infant stage and safe and potent adjuvants for skin vaccination remain largely undefined. We have shown that laser technologies including both fractional and non-fractional lasers can greatly augment vaccine-induced immune response without incurring any significant local and systemic side effects. Laser illumination at specific settings can accelerate the motility of antigen-presenting cells or trigger release of ‘danger’ signals stimulating the immune system. Moreover, several other groups including the authors explore laser technologies for needle-free transcutaneous vaccine delivery. As these laser-mediated resurfacing technologies are convenient, safe and cost-effective, their new applications in vaccination warrant clinical studies in the very near future. PMID:24127871

Effect of priming/booster immunisation protocols on immune response to canine parvovirus peptide induced by vaccination with a chimaeric plant virus construct.

PubMed

Nicholas, B L; Brennan, F R; Hamilton, W D O; Wakelin, D

2003-06-02

Expression of a 17-mer peptide sequence from canine parvovirus expressed on cowpea mosaic virus (CPMV) to form chimaeric virus particles (CVPs) creates vaccine antigens that elicit strong anti-peptide immune responses in mice. Systemic (subcutaneous, s.c.) immunisation and boosting with such CVP constructs produces IgG(2a) serum antibody responses, while mucosal (intranasal, i.n.) immunisation and boosting elicits intestinal IgA responses. Combinations of systemic and mucosal routes for priming and boosting immunisations were used to examine their influence on the level, type and location of immune response generated to one of these constructs (CVP-1). In all cases, s.c. administration, whether for immunisation or boosting, generated a Th1-biased response, reflected in a predominantly IgG(2a) serum antibody isotype and secretion of IFN-gamma from in vitro-stimulated lymphocytes. Serum antibody responses were greatest in animals primed and boosted subcutaneously, and least in mucosally vaccinated mice. The i.n. exposure also led to IFN-gamma release from in vitro-stimulated cells, but serum IgG(2a) was significantly elevated only in mice primed intranasally and boosted subcutaneously. Peptide- and wild-type CPMV-specific IgA responses in gut lavage fluid were greatest in animals exposed mucosally and least in those primed and boosted subcutaneously or primed subcutaneously and boosted orally. Lymphocytes from immunised mice proliferated in response to in vitro stimulation with CPMV but not with peptide. The predominant secretion of IFN-gamma from all immunising/boosting combinations indicates that the route of vaccination and challenge does not alter the Th1 bias of the response to CVP constructs. However, optimal serum and intestinal antibody responses were achieved by combining s.c. and i.n. administration.

Nanoparticles for transcutaneous vaccination.

PubMed

Hansen, Steffi; Lehr, Claus-Michael

2012-03-01

The living epidermis and dermis are rich in antigen presenting cells (APCs). Their activation can elicit a strong humoral and cellular immune response as well as mucosal immunity. Therefore, the skin is a very attractive site for vaccination, and an intradermal application of antigen may be much more effective than a subcutaneous or intramuscular injection. However, the stratum corneum (SC) is a most effective barrier against the invasion of topically applied vaccines. Products which have reached the stage of clinical testing, avoid this problem by injecting the nano-vaccine intradermally or by employing a barrier disrupting method and applying the vaccine to a relatively large skin area. Needle-free vaccination is desirable from a number of aspects: ease of application, improved patient acceptance and less risk of infection among them. Nanocarriers can be designed in a way that they can overcome the SC. Also incorporation into nanocarriers protects instable antigen from degradation, improves uptake and processing by APCs, and facilitates endosomal escape and nuclear delivery of DNA vaccines. In addition, sustained release systems may build a depot in the tissue gradually releasing antigen which may avoid booster doses. Therefore, nanoformulations of vaccines for transcutaneous immunization are currently a very dynamic field of research. Among the huge variety of nanocarrier systems that are investigated hopes lie on ultra-flexible liposomes, superfine rigid nanoparticles and nanocarriers, which are taken up by hair follicles. The potential and pitfalls associated with these three classes of carriers will be discussed. © 2011 The Authors; Microbial Biotechnology © 2011 Society for Applied Microbiology and Blackwell Publishing Ltd.

Nanoparticles for transcutaneous vaccination

PubMed Central

Hansen, Steffi; Lehr, Claus‐Michael

2012-01-01

Summary The living epidermis and dermis are rich in antigen presenting cells (APCs). Their activation can elicit a strong humoral and cellular immune response as well as mucosal immunity. Therefore, the skin is a very attractive site for vaccination, and an intradermal application of antigen may be much more effective than a subcutaneous or intramuscular injection. However, the stratum corneum (SC) is a most effective barrier against the invasion of topically applied vaccines. Products which have reached the stage of clinical testing, avoid this problem by injecting the nano‐vaccine intradermally or by employing a barrier disrupting method and applying the vaccine to a relatively large skin area. Needle‐free vaccination is desirable from a number of aspects: ease of application, improved patient acceptance and less risk of infection among them. Nanocarriers can be designed in a way that they can overcome the SC. Also incorporation into nanocarriers protects instable antigen from degradation, improves uptake and processing by APCs, and facilitates endosomal escape and nuclear delivery of DNA vaccines. In addition, sustained release systems may build a depot in the tissue gradually releasing antigen which may avoid booster doses. Therefore, nanoformulations of vaccines for transcutaneous immunization are currently a very dynamic field of research. Among the huge variety of nanocarrier systems that are investigated hopes lie on ultra‐flexible liposomes, superfine rigid nanoparticles and nanocarriers, which are taken up by hair follicles. The potential and pitfalls associated with these three classes of carriers will be discussed. PMID:21854553

Dismantling the Taboo against Vaccines in Pregnancy

PubMed Central

de Martino, Maurizio

2016-01-01

Vaccinating pregnant women in order to protect them, the fetus, and the child has become universal in no way at all. Prejudice in health professionals add to fears of women and their families. Both these feelings are not supported by even the smallest scientific data. Harmlessness for the mother and the child has been observed for seasonal, pandemic, or quadrivalent influenza, mono, combined polysaccharide or conjugated meningococcal or pneumococcal, tetanus toxoid, acellular pertussis, human papillomavirus, cholera, hepatitis A, Japanese encephalitis, rabies, anthrax, smallpox, yellow fever, mumps, measles and rubella combined, typhoid fever, inactivated or attenuated polio vaccines, and Bacillus Calmétte Guerin vaccines. Instead, the beneficial effects of influenza vaccine for the mother and the child as well as of pertussis vaccine for the child have been demonstrated. Obstetrician-gynecologists, general practitioners, and midwives must incorporate vaccination into their standard clinical care. Strong communication strategies effective at reducing parental vaccine hesitancy and approval of regulatory agencies for use of vaccines during pregnancy are needed. It must be clear that the lack of pre-licensure studies in pregnant women and, consequently, the lack of a statement about the use of the vaccine in pregnant women does not preclude its use in pregnancy. PMID:27338346

Dismantling the Taboo against Vaccines in Pregnancy.

PubMed

de Martino, Maurizio

2016-06-07

Vaccinating pregnant women in order to protect them, the fetus, and the child has become universal in no way at all. Prejudice in health professionals add to fears of women and their families. Both these feelings are not supported by even the smallest scientific data. Harmlessness for the mother and the child has been observed for seasonal, pandemic, or quadrivalent influenza, mono, combined polysaccharide or conjugated meningococcal or pneumococcal, tetanus toxoid, acellular pertussis, human papillomavirus, cholera, hepatitis A, Japanese encephalitis, rabies, anthrax, smallpox, yellow fever, mumps, measles and rubella combined, typhoid fever, inactivated or attenuated polio vaccines, and Bacillus Calmétte Guerin vaccines. Instead, the beneficial effects of influenza vaccine for the mother and the child as well as of pertussis vaccine for the child have been demonstrated. Obstetrician-gynecologists, general practitioners, and midwives must incorporate vaccination into their standard clinical care. Strong communication strategies effective at reducing parental vaccine hesitancy and approval of regulatory agencies for use of vaccines during pregnancy are needed. It must be clear that the lack of pre-licensure studies in pregnant women and, consequently, the lack of a statement about the use of the vaccine in pregnant women does not preclude its use in pregnancy.

Coverage and Influencing Determinants of Influenza Vaccination in Elderly Patients in a Country with a Poor Vaccination Implementation.

PubMed

Ganczak, Maria; Gil, Karolina; Korzeń, Marcin; Bażydło, Marta

2017-06-20

The seasonal influenza vaccination uptake of the elderly in Poland is one of the lowest in Europe. Objective : to assess the vaccination coverage and influencing determinants in patients ≥65 years of age. A cross-sectional study was conducted (November 2015-April 2016) among consecutive patients admitted to a municipal hospital located in the city of Szczecin, North-west Poland. Patients completed researcher-administered, anonymous questionnaires on socio- demographic data/factors related to the vaccination. Results : The response rate: 92.0%. Among 230 patients (79.6% women, median of age 69 years, range 65-89) who agreed to participate, 34.8% (95% Confidence Interval: 28.6-41.0%) were vaccinated. About 15.7% of respondents had not previously heard about the vaccination; 41.3% of those who stated they were vaccinated or planned on being vaccinated the following year, compared to 19.3% of respondents who stated they were not currently vaccinated ( p < 0.001). A multivariable regression analysis revealed that patient factors, such as younger age (Odds Ratio, OR = 7.69), living in the urban area (OR = 7.69), having comorbidities (OR = 2.70), having a vaccinated family member (OR = 3.57), and being informed about vaccination (OR = 5.00) were each associated with greater odds of being immunized. Willingness for vaccination the next year was strongly associated (OR = 8.59) with vaccination status. Conclusions : The influenza vaccination uptake in the elderly population in Poland is disturbingly low. Improved education strategies are needed to increase the uptake. Vaccinated respondents are more likely to plan on being vaccinated the following year. Future interventions related to maximizing vaccination coverage should be more tailored, focusing especially on older patients living in rural areas.

GLA-SE, a Synthetic Toll-like Receptor 4 Agonist, Enhances T-Cell Responses to Influenza Vaccine in Older Adults

PubMed Central

Behzad, Hayedeh; Huckriede, Anke L. W.; Haynes, Laura; Gentleman, Beth; Coyle, Krysta; Wilschut, Jan C.; Kollmann, Tobias R.; Reed, Steven G.

2012-01-01

Background. The decline in influenza vaccine efficacy in older adults is associated with a limited ability of current split-virus vaccines (SVVs) to stimulate cytotoxic T lymphocyte (CTL) responses required for clinical protection against influenza. Methods. The Toll-like receptor 4 agonist glucopyranosyl lipid adjuvant–stable emulsion (GLA-SE) was combined with SVV to stimulate peripheral blood mononuclear cells (PBMCs) in vitro to determine the cytokine response in dendritic cell subsets. Stimulated PBMCs were then challenged with live influenza virus to mimic the response to natural infection following vaccination, using previously identified T-cell correlates of protection. Results. GLA-SE significantly increased the proportion of myeloid dendritic cells that produced tumor necrosis factor α, interleukin 6, and interleukin 12. When combined with SVV to stimulate PBMCs in vitro, this effect of GLA-SE was shown to regulate a T-helper 1 cell response upon challenge with live influenza virus; interleukin 10 production was suppressed, thus significantly increasing the interferon γ to interleukin 10 ratio and the cytolytic (granzyme B) response to influenza virus challenge, both of which have been shown to correlate with protection against influenza in older adults. Conclusions. Our findings suggest that a novel adjuvant, GLA-SE, combined with standard SVV has the potential to significantly improve vaccine-mediated protection against influenza in older adults. PMID:22147791

The contribution of vaccination to global health: past, present and future.

PubMed

Greenwood, Brian

2014-01-01

Vaccination has made an enormous contribution to global health. Two major infections, smallpox and rinderpest, have been eradicated. Global coverage of vaccination against many important infectious diseases of childhood has been enhanced dramatically since the creation of WHO's Expanded Programme of Immunization in 1974 and of the Global Alliance for Vaccination and Immunization in 2000. Polio has almost been eradicated and success in controlling measles makes this infection another potential target for eradication. Despite these successes, approximately 6.6 million children still die each year and about a half of these deaths are caused by infections, including pneumonia and diarrhoea, which could be prevented by vaccination. Enhanced deployment of recently developed pneumococcal conjugate and rotavirus vaccines should, therefore, result in a further decline in childhood mortality. Development of vaccines against more complex infections, such as malaria, tuberculosis and HIV, has been challenging and achievements so far have been modest. Final success against these infections may require combination vaccinations, each component stimulating a different arm of the immune system. In the longer term, vaccines are likely to be used to prevent or modulate the course of some non-infectious diseases. Progress has already been made with therapeutic cancer vaccines and future potential targets include addiction, diabetes, hypertension and Alzheimer's disease.

Potentiation of anthrax vaccines using protective antigen-expressing viral replicon vectors.

PubMed

Wang, Hai-Chao; An, Huai-Jie; Yu, Yun-Zhou; Xu, Qing

2015-02-01

DNA vaccines require improvement for human use because they are generally weak stimulators of the immune system in humans. The efficacy of DNA vaccines can be improved using a viral replicon as vector to administer antigen of pathogen. In this study, we comprehensively evaluated the conventional non-viral DNA, viral replicon DNA or viral replicon particles (VRP) vaccines encoding different forms of anthrax protective antigen (PA) for specific immunity and protective potency against anthrax. Our current results clearly suggested that these viral replicon DNA or VRP vaccines derived from Semliki Forest virus (SFV) induced stronger PA-specific immune responses than the conventional non-viral DNA vaccines when encoding the same antigen forms, which resulted in potent protection against challenge with the Bacillus anthracis strain A16R. Additionally, the naked PA-expressing SFV replicon DNA or VRP vaccines without the need for high doses or demanding particular delivery regimens elicited robust immune responses and afforded completely protective potencies, which indicated the potential of the SFV replicon as vector of anthrax vaccines for use in clinical application. Therefore, our results suggest that these PA-expressing SFV replicon DNA or VRP vaccines may be suitable as candidate vaccines against anthrax. Copyright © 2015 Elsevier B.V. All rights reserved.

Impact of Video Education on Influenza Vaccination in Pregnancy.

PubMed

Goodman, Kenneth; Mossad, Sherif B; Taksler, Glen B; Emery, Jonathan; Schramm, Sarah; Rothberg, Michael B

2015-01-01

Despite influenza vaccination being an integral part of prenatal care, vaccination rates remain low. To evaluate the impact of pre-visit video education on patients' vaccination health beliefs and vaccination rate. From November 2013-January 2014 unvaccinated patients seen for routine prenatal carewere randomized into 2 study groups: pre-visit vaccination video education or control. Pre- and post-video health beliefs were assessed on a 5-point scale, and unvaccinated participants were subsequently interviewed by phone. In 105 randomized participants, intervention positively influenced health beliefs, as demonstrated by differences in mean pre- versus post-video scores for intervention versus control: vaccination may harm mother (difference = -0.05, p = 0.009) and baby (difference = -0.44, p = 0.015), and vaccination can protect mother (difference = 0.49, p = 0.003) and baby (difference = 0.59, p = 0.001). Vaccination rates were 28% intervention and 25% control (p = 0.70). Provider recommendation was associated with vaccination (47% if recommended vs. 12% if not, p < 0.001). Phone interviews revealed susceptibility, to influenza and vaccine safety as primary reasons for remaining unvaccinated. Video education positively influenced vaccination health beliefs without impacting vaccination rates. Physician's recommendation was strongly associated with participant's decision to become vaccinated and may be most effective when emphasizing influenza vaccination's protective impact on the newborn,.

Vaccines to combat river blindness: expression, selection and formulation of vaccines against infection with Onchocerca volvulus in a mouse model

PubMed Central

Hess, Jessica A.; Zhan, Bin; Bonne-Année, Sandra; Deckman, Jessica M.; Bottazzi, Maria Elena; Hotez, Peter J.; Klei, Thomas R.; Lustigman, Sara; Abraham, David

2014-01-01

Human onchocerciasis is a neglected tropical disease caused by Onchocerca volvulus and an important cause of blindness and chronic disability in the developing world. Although mass drug administration of ivermectin has had a profound effect on control of the disease, additional tools are critically needed including the need for a vaccine against onchocerciasis. The objectives of the present study were to: (i) select antigens with known vaccine pedigrees as components of a vaccine; (ii) produce the selected vaccine antigens under controlled conditions, using two expression systems and in one laboratory and (iii) evaluate their vaccine efficacy using a single immunization protocol in mice. In addition, we tested the hypothesis that joining protective antigens as a fusion protein or in combination, into a multivalent vaccine, would improve the ability of the vaccine to induce protective immunity. Out of eight vaccine candidates tested in this study, Ov-103, Ov-RAL-2 and Ov-CPI-2M were shown to reproducibly induce protective immunity when administered individually, as fusion proteins or in combination. Although there was no increase in the level of protective immunity induced by combining the antigens into one vaccine, these antigens remain strong candidates for inclusion in a vaccine to control onchocerciasis in humans. PMID:24907553

Particle-based vaccines for HIV-1 infection.

PubMed

Young, Kelly R; Ross, Ted M

2003-06-01

The use of live-attenuated viruses as vaccines has been successful for the control of viral infections. However, the development of an effective vaccine against the human immunodeficiency virus (HIV) has proven to be a challenge. HIV infects cells of the immune system and results in a severe immunodeficiency. In addition, the ability of the virus to adapt to immune pressure and the ability to reside in an integrated form in host cells present hurdles for vaccinologists to overcome. A particle-based vaccine strategy has promise for eliciting high titer, long-lived, immune responses to a diverse number of viral epitopes from different HIV antigens. Live-attenuated viruses are effective at generating both cellular and humoral immunity, however, a live-attenuated vaccine for HIV is problematic. The possibility of a live-attenuated vaccine to revert to a pathogenic form or recombine with a wild-type or defective virus in an infected individual is a drawback to this approach. Therefore, these vaccines are currently only being tested in non-human primate models. Live-attenuated vaccines are effective in stimulating immunity, however challenged animals rarely clear viral infection and the degree of attenuation directly correlates with the protection of animals from disease. Another particle-based vaccine approach for HIV involves the use of virus-like particles (VLPs). VLPs mimic the viral particle without causing an immunodeficiency disease. HIV-like particles (HIV-LP) are defined as self-assembling, non-replicating, nonpathogenic, genomeless particles that are similar in size and conformation to intact virions. A variety of VLPs for both HIV and SIV are currently in pre-clinical and clinical trials. This review focuses on the current knowledge regarding the immunogenicity and safety of particle-based vaccine strategies for HIV-1.

Effects of Toll-Like Receptor Stimulation on Eosinophilic Infiltration in Lungs of BALB/c Mice Immunized with UV-Inactivated Severe Acute Respiratory Syndrome-Related Coronavirus Vaccine

PubMed Central

Iwata-Yoshikawa, Naoko; Uda, Akihiko; Suzuki, Tadaki; Tsunetsugu-Yokota, Yasuko; Sato, Yuko; Morikawa, Shigeru; Tashiro, Masato; Sata, Tetsutaro; Hasegawa, Hideki

2014-01-01

-like receptor (TLR) agonists to reduce the side effects of UV-inactivated SARS-CoV vaccination in a BALB/c mouse model was tested, using the mouse-passaged Frankfurt 1 isolate of SARS-CoV. We found that TLR stimulation reduced the high level of eosinophilic infiltration that occurred in the lungs of mice immunized with UV-inactivated SARS-CoV. Microarray analysis revealed that genes associated with chemotaxis, eosinophil migration, eosinophilia, and cell movement and the polarization of Th2 cells were upregulated in UV-inactivated SARS-CoV-immunized mice. This study may be helpful for elucidating the pathogenesis underlying eosinophilic infiltration resulting from immunization with inactivated vaccine. PMID:24850731

In-depth genome analyses of viruses from vaccine-derived rabies cases and corresponding live-attenuated oral rabies vaccines.

PubMed

Pfaff, Florian; Müller, Thomas; Freuling, Conrad M; Fehlner-Gardiner, Christine; Nadin-Davis, Susan; Robardet, Emmanuelle; Cliquet, Florence; Vuta, Vlad; Hostnik, Peter; Mettenleiter, Thomas C; Beer, Martin; Höper, Dirk

2018-02-10

Live-attenuated rabies virus strains such as those derived from the field isolate Street Alabama Dufferin (SAD) have been used extensively and very effectively as oral rabies vaccines for the control of fox rabies in both Europe and Canada. Although these vaccines are safe, some cases of vaccine-derived rabies have been detected during rabies surveillance accompanying these campaigns. In recent analysis it was shown that some commercial SAD vaccines consist of diverse viral populations, rather than clonal genotypes. For cases of vaccine-derived rabies, only consensus sequence data have been available to date and information concerning their population diversity was thus lacking. In our study, we used high-throughput sequencing to analyze 11 cases of vaccine-derived rabies, and compared their viral population diversity to the related oral rabies vaccines using pairwise Manhattan distances. This extensive deep sequencing analysis of vaccine-derived rabies cases observed during oral vaccination programs provided deeper insights into the effect of accidental in vivo replication of genetically diverse vaccine strains in the central nervous system of target and non-target species under field conditions. The viral population in vaccine-derived cases appeared to be clonal in contrast to their parental vaccines. The change from a state of high population diversity present in the vaccine batches to a clonal genotype in the affected animal may indicate the presence of a strong bottleneck during infection. In conclusion, it is very likely that these few cases are the consequence of host factors and not the result of the selection of a more virulent genotype. Furthermore, this type of vaccine-derived rabies leads to the selection of clonal genotypes and the selected variants were genetically very similar to potent SAD vaccines that have undergone a history of in vitro selection. Copyright © 2018. Published by Elsevier Ltd.

Strategies and actions of multi-purpose health communication on vaccine preventable infectious diseases in order to increase vaccination coverage in the population: The ESCULAPIO project

PubMed Central

Bonanni, Paolo; Lauri, Sara; Tiscione, Emilia; Levi, Miriam; Prato, Rosa; Fortunato, Francesca; Martinelli, Domenico; Gasparini, Roberto; Panatto, Donatella; Amicizia, Daniela; Coppola, Rosa Cristina; Vitale, Francesco; Iannazzo, Stefania

2017-01-01

ABSTRACT The ESCULAPIO Project aims at increasing awareness on vaccine preventable infectious diseases (VPID) and vaccinations in different target populations and to spread the culture of prevention. Information/training interventions on VPID have been developed and health promotion activities for the general population, students and their parents, teachers and health care workers (HCWs) were set up. In Tuscany, educational courses on VPID in high schools were organized and students were stimulated to prepare informative materials on VPID for lower grade school pupils. In Liguria, an educational card game (named ‘Vaccine at the Fair’) was presented to children of primary schools. Stands in shopping centers were used in Palermo to distribute the regional vaccination schedule and gadgets, also providing indications on reliable websites where to find correct information on vaccinations. A music video played by health care workers (HCWs) was created and used in the University Hospital of Cagliari to promote the anti-flu vaccination campaign in HCWs. In Apulia, meetings with the general population were organized to collect controversial issues about vaccinations and a national call center was launched to create a direct line from the general population to experts in vaccines and vaccination strategies. In Veneto, meetings in the birth centers and home visits for subjects refusing vaccination have been organized. All activities are useful and effective tools to increase knowledge about VPID and confidence in vaccination, which are crucial aspects in order to increase vaccine uptake. The project was funded by the Italian Ministry of Health, Center for Disease Prevention and Control (CCM) in 2013. PMID:28215120

Strategies and actions of multi-purpose health communication on vaccine preventable infectious diseases in order to increase vaccination coverage in the population: The ESCULAPIO project.

PubMed

Bechini, Angela; Bonanni, Paolo; Lauri, Sara; Tiscione, Emilia; Levi, Miriam; Prato, Rosa; Fortunato, Francesca; Martinelli, Domenico; Gasparini, Roberto; Panatto, Donatella; Amicizia, Daniela; Coppola, Rosa Cristina; Pellizzari, Barbara; Tabacchi, Garden; Costantino, Claudio; Vitale, Francesco; Iannazzo, Stefania; Boccalini, Sara

2017-02-01

The ESCULAPIO Project aims at increasing awareness on vaccine preventable infectious diseases (VPID) and vaccinations in different target populations and to spread the culture of prevention. Information/training interventions on VPID have been developed and health promotion activities for the general population, students and their parents, teachers and health care workers (HCWs) were set up. In Tuscany, educational courses on VPID in high schools were organized and students were stimulated to prepare informative materials on VPID for lower grade school pupils. In Liguria, an educational card game (named 'Vaccine at the Fair') was presented to children of primary schools. Stands in shopping centers were used in Palermo to distribute the regional vaccination schedule and gadgets, also providing indications on reliable websites where to find correct information on vaccinations. A music video played by health care workers (HCWs) was created and used in the University Hospital of Cagliari to promote the anti-flu vaccination campaign in HCWs. In Apulia, meetings with the general population were organized to collect controversial issues about vaccinations and a national call center was launched to create a direct line from the general population to experts in vaccines and vaccination strategies. In Veneto, meetings in the birth centers and home visits for subjects refusing vaccination have been organized. All activities are useful and effective tools to increase knowledge about VPID and confidence in vaccination, which are crucial aspects in order to increase vaccine uptake. The project was funded by the Italian Ministry of Health, Center for Disease Prevention and Control (CCM) in 2013.

Alternative early life vaccination programs for companion animals.

PubMed

Poulet, H

2007-07-01

An experimental challenge study of multicomponent vaccination of kittens is reported. Seven-to-nine week old, specific pathogen-free kittens received two injections (4 weeks apart) of non-adjuvanted, multicomponent vaccine formulated at the minimum protective dose. Kittens were challenged at 4 weeks or 1 year post-vaccination with individual infectious agents. Vaccination induced complete protection against challenge from feline parvovirus on both occasions, but at 1 year, the protection against feline herpesvirus, feline calicivirus and Chlamydophila felis was not as strong as 4 weeks after vaccination. This demonstration of a decline in protective immunity at the normal time of administration of the first booster vaccine suggests that earlier administration of this booster (at 4-6 months of age) may provide better protection. The effect of maternally derived antibody (MDA) on kitten vaccination was determined by conducting an identical experiment but with kittens born to queens vaccinated during pregnancy. Serum antibody titres to specific vaccine components were measured in these kittens on day 0 (time of first vaccination), day 28 (time of second vaccination) and day 42. There was heterogeneity in transfer of MDA to kittens within a litter, and between litters. MDA may neutralize the serological response of kittens on the first, and occasionally the second, occasion of vaccination when vaccination is performed at 8 and 12 weeks of age. This finding underpins recent recommendations that the final vaccination in the primary series be administered at 16 weeks of age.

Stability and pre-formulation development of a plant-produced anthrax vaccine candidate.

PubMed

Jones, R Mark; Burke, Michael; Dubose, Devon; Chichester, Jessica A; Manceva, Slobodanka; Horsey, April; Streatfield, Stephen J; Breit, Jeff; Yusibov, Vidadi

2017-10-04

Second generation anthrax vaccines focus on the use of recombinant protective antigen (rPA) to elicit a strong, toxin neutralizing antibody responses in immunized subjects. The main difference between the rPA vaccines compared to the current licensed vaccine, anthrax vaccine absorbed (AVA), is the rPA vaccines are highly purified preparations of only rPA. These second generation rPA vaccines strive to elicit strong immune responses with substantially fewer doses than AVA while provoking less side effects. Many of the rPA candidates have shown to be effective in pre-clinical studies, but most of the second generation molecules have stability issues which reduce their efficacy over time. These stability issues are evident even under refrigerated conditions and thus emphasis has been directed to stabilizing the rPA molecule and determining an optimized final formulation. Stabilization of vaccines for long-term storage is a major challenge in the product development life cycle. The effort required to identify suitable formulations can be slow and expensive. The ideal storage for stockpiled vaccines would allow the candidate to withstand years of storage at ambient temperatures. The Fraunhofer Center for Molecular Biotechnology is developing a plant-produced rPA vaccine candidate that shows instability when stored under refrigerated conditions in a solution, as is typical for rPA vaccines. Increased stability of our plant-produced rPA vaccine candidate was achieved in a spray dried powder formulation that could eliminate the need for conventional cold chain allowing greater confidence to stockpile vaccine for civilian and military biodefense. Copyright © 2017 Elsevier Ltd. All rights reserved.

Egg quality in laying hens exposed to Mycoplasma gallisepticum F-strain attenuated vaccine.

PubMed

Machado, L D S; Santos, F F D; Togashi, C K; Abreu, D L D C; Pimentel, J C; Sesti, L; Pereira, V L D A; Nascimento, E R D

2017-04-01

Mycoplasma gallisepticum causes coughing, ocular and nasal discharge, reduction in feed intake, lower and uneven growth, decline in egg production and quality, and increase in mortality. Among the attenuated vaccination strains, MGF can reduce clinical signs and lesions in layer hens, stimulate immune responses of cellular and humoral basis, act as an instrument of competitive exclusion in relation to field strains, and reduce the use of antimicrobials. This study aimed to investigate the effects of attenuated MG F-strain vaccination on egg quality in 3 groups of 30 hens each, being one control and 2 vaccinated. Vaccination was applied by ocular route at 8 and 12 wk of age. Comparisons were made among unvaccinated hens; vaccinated at 8 wk of age; and vaccinated at 8 and 12 wk of age. There were no statistical differences in eggshell thickness and weight among groups. Eggs from twice vaccinated birds yielded a Haugh unit significantly lower than the other groups without affecting egg classification. There was no significant difference in ELISA results between the vaccinated groups. © 2016 Poultry Science Association Inc.

Memory T cells and vaccines.

PubMed

Esser, Mark T; Marchese, Rocio D; Kierstead, Lisa S; Tussey, Lynda G; Wang, Fubao; Chirmule, Narendra; Washabaugh, Michael W

2003-01-17

T lymphocytes play a central role in the generation of a protective immune response in many microbial infections. After immunization, dendritic cells take up microbial antigens and traffic to draining lymph nodes where they present processed antigens to naïve T cells. These naïve T cells are stimulated to proliferate and differentiate into effector and memory T cells. Activated, effector and memory T cells provide B cell help in the lymph nodes and traffic to sites of infection where they secrete anti-microbial cytokines and kill infected cells. At least two types of memory cells have been defined in humans based on their functional and migratory properties. T central-memory (T(CM)) cells are found predominantly in lymphoid organs and can not be immediately activated, whereas T effector-memory (T(EM)) cells are found predominantly in peripheral tissue and sites of inflammation and exhibit rapid effector function. Most currently licensed vaccines induce antibody responses capable of mediating long-term protection against lytic viruses such as influenza and small pox. In contrast, vaccines against chronic pathogens that require cell-mediated immune responses to control, such as malaria, Mycobacterium tuberculosis (TB), human immunodeficiency virus (HIV) and hepatitis C virus (HCV), are currently not available or are ineffective. Understanding the mechanisms by which long-lived cellular immune responses are generated following vaccination should facilitate the development of safe and effective vaccines against these emerging diseases. Here, we review the current literature with respect to memory T cells and their implications to vaccine development.

Curative potential of GM-CSF-secreting tumor cell vaccines on established orthotopic liver tumors: mechanisms for the superior antitumor activity of live tumor cell vaccines.

PubMed

Tai, Kuo-Feng; Chen, Ding-Shinn; Hwang, Lih-Hwa

2004-01-01

In preclinical studies, tumor cells genetically engineered to secrete cytokines, hereafter referred to as tumor cell vaccines, can often generate systemic antitumor immunity. This study investigated the therapeutic effects of live or irradiated tumor cell vaccines that secrete granulocyte-macrophage colony-stimulating factor (GM-CSF) on established orthotopic liver tumors. Experimental results indicated that two doses (3 x 10(7) cells per dose) of irradiated tumor cell vaccines were therapeutically ineffective, whereas one dose (3 x 10(6) cells) of live tumor cell vaccines caused complete tumor regression. In vivo depletion of CD8+ T cells, but not natural killer cells, restored tumor formation in the live vaccine-treated animals. Additionally, the treatment of cells with live vaccine induced markedly higher levels of cytotoxic T lymphocyte activity than the irradiated vaccines in the draining lymph nodes. The higher levels of cytokine and antigen loads could partly explain the superior antitumor activity of live tumor cell vaccines, but other unidentified mechanisms could also play a role in the early T cell activation in the lymph nodes. A protocol using multiple and higher dosages of irradiated tumor cell vaccines also caused significant regression of liver tumors. These results suggest that the GM-CSF-secreting tumor cell vaccines are highly promising for orthotopic liver tumors if higher levels of immune responses are elicited during early tumor development. Copyright 2004 National Science Council, ROC and S. Karger AG, Basel

Socialization, Indifference, and Convenience: Exploring the Uptake of Influenza Vaccine Among Medical Students and Early Career Doctors.

PubMed

Edge, Rhiannon; Goodwin, Dawn; Isba, Rachel; Keegan, Thomas

2017-11-01

The Chief Medical Officer recommends that all health care workers receive an influenza vaccination annually. High vaccination coverage is believed to be the best protection against the spread of influenza within a hospital, although uptake by health care workers remains low. We conducted semistructured interviews with seven medical students and nine early career doctors, to explore the factors informing their influenza vaccination decision making. Data collection and analysis took place iteratively, until theoretical saturation was achieved, and a thematic analysis was performed. Socialization was important although its effects were attenuated by participants' previous experiences and a lack of clarity around the risks and benefits of vaccination. Many participants did not have strong intentions regarding vaccination. There was considerable disparity between an individual's opinion of the vaccine, their intentions, and their vaccination status. The indifference demonstrated here suggests few are strongly opposed to the vaccination-there is potential to increase vaccination coverage.

Against Strong Ethical Parity: Situated Cognition Theses and Transcranial Brain Stimulation.

PubMed

Heinrichs, Jan-Hendrik

2017-01-01

According to a prominent suggestion in the ethics of transcranial neurostimulation the effects of such devices can be treated as ethically on par with established, pre-neurotechnological alterations of the mind. This parity allegedly is supported by situated cognition theories showing how external devices can be part of a cognitive system. This article will evaluate this suggestion. It will reject the claim, that situated cognition theories support ethical parity. It will however point out another reason, why external carriers or modifications of the mental might come to be considered ethically on par with internal carriers. Section "Why Could There Be Ethical Parity between Neural Tissue and External Tools?" presents the ethical parity theses between external and internal carriers of the mind as well as neurotechnological alterations and established alterations. Section "Extended, Embodied, Embedded: Situated Cognition as a Relational Thesis" will elaborate the different situated cognition approaches and their relevance for ethics. It will evaluate, whether transcranial stimulation technologies are plausible candidates for situated cognition theses. Section "On the Ethical Relevance of Situated Cognition Theses" will discuss criteria for evaluating whether a cognitive tool is deeply embedded with a cognitive system and apply these criteria to transcranial brain stimulation technologies. Finally it will discuss the role diverse versions of situated cognition theory can play in the ethics of altering mental states, especially the ethics of transcranial brain stimulation technologies.

Current State in the Development of Candidate Therapeutic HPV Vaccines

PubMed Central

Yang, Andrew; Jeang, Jessica; Cheng, Kevin; Cheng, Ting; Yang, Benjamin; Wu, T.-C.; Hung, Chien-Fu

2016-01-01

Summary The identification of human papillomavirus (HPV) as an etiological factor for HPV-associated malignancies creates the opportunity to control these cancers through vaccination. Currently, available preventive HPV vaccines have not yet demonstrated strong evidences for therapeutic effects against established HPV infections and lesions. Furthermore, HPV infections remain extremely common. Thus, there is urgent need for therapeutic vaccines to treat existing HPV infections and HPV-associated diseases. Therapeutic vaccines differ from preventive vaccines in that they are aimed at generating cell-mediated immunity rather than neutralizing antibodies. The HPV-encoded early proteins, especially oncoproteins E6 and E7, form ideal targets for therapeutic HPV vaccines since they are consistently expressed in HPV-associated malignancies and precancerous lesions, playing crucial roles in the generation and maintenance of HPV-associated disease. Our review will cover various therapeutic vaccines in development for the treatment of HPV-associated lesions and cancers. Furthermore, we review strategies to enhance vaccine efficacy and the latest clinical trials on therapeutic HPV vaccines. PMID:26901118

HPV vaccine stimulates cytotoxic activity of killer dendritic cells and natural killer cells against HPV-positive tumour cells

PubMed Central

Van den Bergh, Johan M J; Guerti, Khadija; Willemen, Yannick; Lion, Eva; Cools, Nathalie; Goossens, Herman; Vorsters, Alex; Van Tendeloo, Viggo F I; Anguille, Sébastien; Van Damme, Pierre; Smits, Evelien L J M

2014-01-01

Cervarix™ is approved as a preventive vaccine against infection with the human papillomavirus (HPV) strains 16 and 18, which are causally related to the development of cervical cancer. We are the first to investigate in vitro the effects of this HPV vaccine on interleukin (IL)-15 dendritic cells (DC) as proxy of a naturally occurring subset of blood DC, and natural killer (NK) cells, two innate immune cell types that play an important role in antitumour immunity. Our results show that exposure of IL-15 DC to the HPV vaccine results in increased expression of phenotypic maturation markers, pro-inflammatory cytokine production and cytotoxic activity against HPV-positive tumour cells. These effects are mediated by the vaccine adjuvant, partly through Toll-like receptor 4 activation. Next, we demonstrate that vaccine-exposed IL-15 DC in turn induce phenotypic activation of NK cells, resulting in a synergistic cytotoxic action against HPV-infected tumour cells. Our study thus identifies a novel mode of action of the HPV vaccine in boosting innate immunity, including killing of HPV-infected cells by DC and NK cells. PMID:24979331

Construction and analysis of experimental DNA vaccines against megalocytivirus.

PubMed

Zhang, Min; Hu, Yong-Hua; Xiao, Zhi-Zhong; Sun, Yun; Sun, Li

2012-11-01

Iridoviruses are large double-stranded DNA viruses with icosahedral capsid. The Iridoviridae family contains five genera, one of which is Megalocytivirus. Megalocytivirus has emerged in recent years as an important pathogen to a wide range of marine and freshwater fish. In this study, we aimed at developing effective genetic vaccines against megalocytivirus affecting farmed fish in China. For this purpose, we constructed seven DNA vaccines based on seven genes of rock bream iridovirus isolate 1 from China (RBIV-C1), a megalocytivirus with a host range that includes Japanese flounder (Paralichthys olivaceus) and turbot (Scophthalmus maximus). The protective potentials of these vaccines were examined in a turbot model. The results showed that after vaccination via intramuscular injection, the vaccine plasmids were distributed in spleen, kidney, muscle, and liver, and transcription of the vaccine genes and production of the vaccine proteins were detected in these tissues. Following challenge with a lethal-dose of RBIV-C1, fish vaccinated with four of the seven DNA vaccines exhibited significantly higher levels of survival compared to control fish. Of these four protective DNA vaccines, pCN86, which is a plasmid that expresses an 86-residue viral protein, induced the highest protection. Immunological analysis showed that pCN86 was able to (i) stimulate the respiratory burst of head kidney macrophages at 14 d, 21 d, and 28 d post-vaccination, (ii) upregulate the expression of immune relevant genes involved in innate and adaptive immunity, and (iii) induce production of serum antibodies that, when incubated with RBIV-C1 before infection, significantly reduced viral loads in kidney and spleen following viral infection of turbot. Taken together, these results indicate that pCN86 is an effective DNA vaccine that may be used in the control of megalocytivirus-associated diseases in aquaculture. Copyright © 2012 Elsevier Ltd. All rights reserved.

Genetic cancer vaccines: current status and perspectives.

PubMed

Aurisicchio, Luigi; Ciliberto, Gennaro

2012-08-01

The recent approval of the first therapeutic cancer vaccine by the US Regulatory Agency represents a breakthrough event in the history of cancer treatment. The past scepticism towards this type of therapeutic intervention is now replaced by great expectations. The field is now moving towards the development of alternative vaccination technologies, which are capable of generating stronger, more durable and efficient immune responses against specific tumour-associated antigens (TAAs) in combination with cheaper and more standardised manufacturing. In this context, genetic vaccines are emerging among the most promising methodologies. Several evidences point to combinations of different genetic immunisation modalities (heterologous prime/boost) as a powerful approach to induce superior immune responses and achieve greater clinical efficacy. In this review, we provide an overview of the current status of development of genetic cancer vaccines with particular emphasis on adenoviral vector prime/DNA boost vaccination schedules. We believe that therapeutic genetic cancer vaccines have the strong potential to become an established therapeutic modality for cancer in next coming years, in a manner similar to what have now become monoclonal antibodies.

Vaccines in development against West Nile virus.

PubMed

Brandler, Samantha; Tangy, Frederic

2013-09-30

West Nile encephalitis emerged in 1999 in the United States, then rapidly spread through the North American continent causing severe disease in human and horses. Since then, outbreaks appeared in Europe, and in 2012, the United States experienced a new severe outbreak reporting a total of 5,387 cases of West Nile virus (WNV) disease in humans, including 243 deaths. So far, no human vaccine is available to control new WNV outbreaks and to avoid worldwide spreading. In this review, we discuss the state-of-the-art of West Nile vaccine development and the potential of a novel safe and effective approach based on recombinant live attenuated measles virus (MV) vaccine. MV vaccine is a live attenuated negative-stranded RNA virus proven as one of the safest, most stable and effective human vaccines. We previously described a vector derived from the Schwarz MV vaccine strain that stably expresses antigens from emerging arboviruses, such as dengue, West Nile or chikungunya viruses, and is strongly immunogenic in animal models, even in the presence of MV pre-existing immunity. A single administration of a recombinant MV vaccine expressing the secreted form of WNV envelope glycoprotein elicited protective immunity in mice and non-human primates as early as two weeks after immunization, indicating its potential as a human vaccine.

Molecular approaches to fish vaccines

USGS Publications Warehouse

Winton, J.R.

1998-01-01

For more than 50 years, researchers have tested a variety of killed, attenuated, and subunit preparations for control offish diseases. The earliest fish vaccines used killed preparations containing whole bacteria, viruses, or parasites and today, several bacterins have become commercially successful with more expected as improved delivery systems and adjuvants are realized. Live, attenuated vaccines have been developed by serial passage of a pathogen in culture or by using naturally occurring mutants and cross-reacting strains. These generally offer excellent protection and are cost-effective, but concerns about residual virulence or their effects on other aquatic species make them difficult candidates for licensing. In recent years, the tools of molecular biology have been applied to construction of a variety of recombinant, engineered, or subunit vaccines for fish. Among the approaches to be discussed are: attenuated strains of viruses and bacteria created by deletion of specific genes associated with virulence, in vitro synthesis of protective antigens from genes cloned into E. coli or baculovirus expression systems, chemical synthesis of peptides that represent protective epitopes, and direct immunization with DNA coding for protective antigens. Preparations representing each of these approaches have been tested in laboratory or field trials with various results and such vaccines promise to be safe and relatively inexpensive if they are able to provide protection when delivered by immersion. A significant advantage of genetically engineered vaccines is the ability to construct multivalent preparations that can protect fish against several pathogens or different strains of the same pathogen. While many of these novel vaccine strategies have been effective at stimulating specific immunity in the laboratory, more work is needed to develop better delivery systems and to overcome potential regulatory concerns.

Construction and Evaluation of Novel Rhesus Monkey Adenovirus Vaccine Vectors

PubMed Central

Abbink, Peter; Maxfield, Lori F.; Ng'ang'a, David; Borducchi, Erica N.; Iampietro, M. Justin; Bricault, Christine A.; Teigler, Jeffrey E.; Blackmore, Stephen; Parenteau, Lily; Wagh, Kshitij; Handley, Scott A.; Zhao, Guoyan; Virgin, Herbert W.; Korber, Bette

2014-01-01

ABSTRACT Adenovirus vectors are widely used as vaccine candidates for a variety of pathogens, including HIV-1. To date, human and chimpanzee adenoviruses have been explored in detail as vaccine vectors. The phylogeny of human and chimpanzee adenoviruses is overlapping, and preexisting humoral and cellular immunity to both are exhibited in human populations worldwide. More distantly related adenoviruses may therefore offer advantages as vaccine vectors. Here we describe the primary isolation and vectorization of three novel adenoviruses from rhesus monkeys. The seroprevalence of these novel rhesus monkey adenovirus vectors was extremely low in sub-Saharan Africa human populations, and these vectors proved to have immunogenicity comparable to that of human and chimpanzee adenovirus vaccine vectors in mice. These rhesus monkey adenoviruses phylogenetically clustered with the poorly described adenovirus species G and robustly stimulated innate immune responses. These novel adenoviruses represent a new class of candidate vaccine vectors. IMPORTANCE Although there have been substantial efforts in the development of vaccine vectors from human and chimpanzee adenoviruses, far less is known about rhesus monkey adenoviruses. In this report, we describe the isolation and vectorization of three novel rhesus monkey adenoviruses. These vectors exhibit virologic and immunologic characteristics that make them attractive as potential candidate vaccine vectors for both HIV-1 and other pathogens. PMID:25410856

Tumor lysate-based vaccines: on the road to immunotherapy for gallbladder cancer.

PubMed

Rojas-Sepúlveda, Daniel; Tittarelli, Andrés; Gleisner, María Alejandra; Ávalos, Ignacio; Pereda, Cristián; Gallegos, Iván; González, Fermín Eduardo; López, Mercedes Natalia; Butte, Jean Michel; Roa, Juan Carlos; Fluxá, Paula; Salazar-Onfray, Flavio

2018-03-29

Immunotherapy based on checkpoint blockers has proven survival benefits in patients with melanoma and other malignancies. Nevertheless, a significant proportion of treated patients remains refractory, suggesting that in combination with active immunizations, such as cancer vaccines, they could be helpful to improve response rates. During the last decade, we have used dendritic cell (DC) based vaccines where DCs loaded with an allogeneic heat-conditioned melanoma cell lysate were tested in a series of clinical trials. In these studies, 60% of stage IV melanoma DC-treated patients showed immunological responses correlating with improved survival. Further studies showed that an essential part of the clinical efficacy was associated with the use of conditioned lysates. Gallbladder cancer (GBC) is a high-incidence malignancy in South America. Here, we evaluated the feasibility of producing effective DCs using heat-conditioned cell lysates derived from gallbladder cancer cell lines (GBCCL). By characterizing nine different GBCCLs and several fresh tumor tissues, we found that they expressed some tumor-associated antigens such as CEA, MUC-1, CA19-9, Erb2, Survivin, and several carcinoembryonic antigens. Moreover, heat-shock treatment of GBCCLs induced calreticulin translocation and release of HMGB1 and ATP, both known to act as danger signals. Monocytes stimulated with combinations of conditioned lysates exhibited a potent increase of DC-maturation markers. Furthermore, conditioned lysate-matured DCs were capable of strongly inducing CD4 + and CD8 + T cell activation, in both allogeneic and autologous cell co-cultures. Finally, in vitro stimulated CD8 + T cells recognize HLA-matched GBCCLs. In summary, GBC cell lysate-loaded DCs may be considered for future immunotherapy approaches.

RNActive® Technology: Generation and Testing of Stable and Immunogenic mRNA Vaccines.

PubMed

Rauch, Susanne; Lutz, Johannes; Kowalczyk, Aleksandra; Schlake, Thomas; Heidenreich, Regina

2017-01-01

Developing effective mRNA vaccines poses certain challenges concerning mRNA stability and ability to induce sufficient immune stimulation and requires a specific panel of techniques for production and testing. Here, we describe the production of stabilized mRNA with enhanced immunogenicity, generated using conventional nucleotides only, by introducing changes to the mRNA sequence and by complexation with the nucleotide-binding peptide protamine (RNActive® technology). Methods described here include the synthesis, purification, and protamine complexation of mRNA vaccines as well as a comprehensive panel of in vitro and in vivo methods for evaluation of vaccine quality and immunogenicity.

Combination Immunotherapy of B16 Melanoma Using Anti–Cytotoxic T Lymphocyte–Associated Antigen 4 (Ctla-4) and Granulocyte/Macrophage Colony-Stimulating Factor (Gm-Csf)-Producing Vaccines Induces Rejection of Subcutaneous and Metastatic Tumors Accompanied by Autoimmune Depigmentation

PubMed Central

van Elsas, Andrea; Hurwitz, Arthur A.; Allison, James P.

1999-01-01

We examined the effectiveness of cytotoxic T lymphocyte–associated antigen 4 (CTLA-4) blockade, alone or in combination with a granulocyte/macrophage colony-stimulating factor (GM-CSF)–expressing tumor cell vaccine, on rejection of the highly tumorigenic, poorly immunogenic murine melanoma B16-BL6. Recently established tumors could be eradicated in 80% (68/85) of the cases using combination treatment, whereas each treatment by itself showed little or no effect. Tumor rejection was dependent on CD8+ and NK1.1+ cells but occurred irrespective of the presence of CD4+ T cells. Mice surviving a primary challenge rejected a secondary challenge with B16-BL6 or the parental B16-F0 line. The same treatment regimen was found to be therapeutically effective against outgrowth of preestablished B16-F10 lung metastases, inducing long-term survival. Of all mice surviving B16-BL6 or B16-F10 tumors after combination treatment, 56% (38/68) developed depigmentation, starting at the site of vaccination or challenge and in most cases progressing to distant locations. Depigmentation was found to occur in CD4-depleted mice, strongly suggesting that the effect was mediated by CTLs. This study shows that CTLA-4 blockade provides a powerful tool to enhance T cell activation and memory against a poorly immunogenic spontaneous murine tumor and that this may involve recruitment of autoreactive T cells. PMID:10430624

Combination immunotherapy of B16 melanoma using anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and granulocyte/macrophage colony-stimulating factor (GM-CSF)-producing vaccines induces rejection of subcutaneous and metastatic tumors accompanied by autoimmune depigmentation.

PubMed

van Elsas, A; Hurwitz, A A; Allison, J P

1999-08-02

We examined the effectiveness of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) blockade, alone or in combination with a granulocyte/macrophage colony-stimulating factor (GM-CSF)-expressing tumor cell vaccine, on rejection of the highly tumorigenic, poorly immunogenic murine melanoma B16-BL6. Recently established tumors could be eradicated in 80% (68/85) of the cases using combination treatment, whereas each treatment by itself showed little or no effect. Tumor rejection was dependent on CD8(+) and NK1.1(+) cells but occurred irrespective of the presence of CD4(+) T cells. Mice surviving a primary challenge rejected a secondary challenge with B16-BL6 or the parental B16-F0 line. The same treatment regimen was found to be therapeutically effective against outgrowth of preestablished B16-F10 lung metastases, inducing long-term survival. Of all mice surviving B16-BL6 or B16-F10 tumors after combination treatment, 56% (38/68) developed depigmentation, starting at the site of vaccination or challenge and in most cases progressing to distant locations. Depigmentation was found to occur in CD4-depleted mice, strongly suggesting that the effect was mediated by CTLs. This study shows that CTLA-4 blockade provides a powerful tool to enhance T cell activation and memory against a poorly immunogenic spontaneous murine tumor and that this may involve recruitment of autoreactive T cells.

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

Although the vaccine research and development network in the United States remains vibrant, its continued success requires maintaining harmonious interaction among its many components. Changing one component is likely to affect the system overall. An examination of case studies of the development of selected vaccines would allow an examination of the network as a whole. This article presents conclusions drawn from the case study review undertaken. Successful development of vaccines is a time-intensive process requiring years of commitment from a network of scientists and a continuum of regulatory and manufacturing entities. We undertook this work to shed light on how well the vaccine development system in the United States performs. The National Vaccine Advisory Committee examined the research and development pathways of several vaccines that reached licensure expeditiously (hepatitis B vaccine, Haemophilus influenzae type b conjugate vaccines); some that became licensed only after considerable delay (oral typhoid Ty21a vaccine, varicella vaccine); some that are at the point of imminent or recent licensure (reassortant Rhesus rotavirus vaccine, which was licensed by the Food and Drug Administration on August 30, 1998) or near submission for licensure (intranasal cold adapted influenza vaccine); and one for which clinical development is slow because of hurdles that must be overcome (respiratory syncytial virus vaccines). Some common themes emerged from the reviews of these vaccine "case histories": the expediting influence of a strong scientific base and rationale; the need for firm quantitation of disease burden and clear identification of target populations; the critical role played by individuals or teams who act as "champions" to overcome the inevitable obstacles; availability of relevant animal models, high-quality reagents and standardized assays to measure immune response; the absolute requirement for well designed, meticulously executed clinical trials of

Factors Associated with Intention to Receive Influenza and Tetanus, Diphtheria, and Acellular Pertussis (Tdap) Vaccines during Pregnancy: A Focus on Vaccine Hesitancy and Perceptions of Disease Severity and Vaccine Safety.

PubMed

Chamberlain, Allison T; Seib, Katherine; Ault, Kevin A; Orenstein, Walter A; Frew, Paula M; Malik, Fauzia; Cortés, Marielysse; Cota, Pat; Whitney, Ellen A S; Flowers, Lisa C; Berkelman, Ruth L; Omer, Saad B

2015-02-25

Improving influenza and tetanus, diphtheria and acellular pertussis (Tdap) vaccine coverage among pregnant women is needed. To assess factors associated with intention to receive influenza and/or Tdap vaccinations during pregnancy with a focus on perceptions of influenza and pertussis disease severity and influenza vaccine safety. Participants were 325 pregnant women in Georgia recruited from December 2012 - April 2013 who had not yet received a 2012/2013 influenza vaccine or a Tdap vaccine while pregnant. Women completed a survey assessing influenza vaccination history, likelihood of receiving antenatal influenza and/or Tdap vaccines, and knowledge, attitudes and beliefs about influenza, pertussis, and their associated vaccines. Seventy-three percent and 81% of women believed influenza and pertussis, respectively, would be serious during pregnancy while 87% and 92% believed influenza and pertussis, respectively, would be serious to their infants. Perception of pertussis severity for their infant was strongly associated with an intention to receive a Tdap vaccine before delivery (p=0.004). Despite perceptions of disease severity for themselves and their infants, only 34% and 44% intended to receive antenatal influenza and Tdap vaccines, respectively. Forty-six percent had low perceptions of safety regarding the influenza vaccine during pregnancy, and compared to women who perceived the influenza vaccine as safe, women who perceived the vaccine as unsafe were less likely to intend to receive antenatal influenza (48% vs. 20%; p < 0.001) or Tdap (53% vs. 33%; p < 0.001) vaccinations. Results from this baseline survey suggest that while pregnant women who remain unvaccinated against influenza within the first three months of the putative influenza season may be aware of the risks influenza and pertussis pose to themselves and their infants, many remain reluctant to receive influenza and Tdap vaccines antenatally. To improve vaccine uptake in the obstetric setting, our

The role of implementation intention formation in promoting hepatitis B vaccination uptake among men who have sex with men.

PubMed

Vet, Raymond; de Wit, John B F; Das, Enny

2014-02-01

This study assessed the separate and joint effects of having a goal intention and the completeness of implementation intention formation on the likelihood of attending an appointment to obtain vaccination against the hepatitis B virus among men who have sex with men (MSM) in the Netherlands. Extending previous research, it was hypothesized that to be effective in promoting vaccination, implementation intention formation not only requires a strong goal intention, but also complete details specifying when, where and how to make an appointment to obtain hepatitis B virus vaccination among MSM. MSM at risk for hepatitis B virus (N = 616), with strong or weak intentions to obtain hepatitis B virus vaccination, were randomly assigned to form an implementation intention or not. Completeness of implementation intentions was rated and hepatitis B virus uptake was assessed through data linkage with the joint vaccination registry of the collaborating Public Health Services. Having a strong goal intention to obtain hepatitis B virus vaccination and forming an implementation intention, each significantly and independently increased the likelihood of MSM obtaining hepatitis B virus vaccination. In addition, MSM who formed complete implementation intentions were more successful in obtaining vaccination (p < 0.01). The formation of complete implementation intentions was promoted by strong goal intentions (p < 0.01).

Next Generation Vaccine Biomarkers workshop October 30–31, 2014 – Ottawa, Canada

PubMed Central

Twine, Susan M; Fulton, Kelly M; Spika, John; Ouellette, Marc; Raven, Jennifer F; Conlan, J Wayne; Krishnan, Lakshmi; Barreto, Luis; Richards, James C

2015-01-01

Vaccine biomarkers are critical to many aspects of vaccine development and licensure, including bridging findings in pre-clinical studies to clinical studies, predicting potential adverse events, and predicting vaccine efficacy. Despite advances in our understanding of various biological pathways, and advances in systems analyses of the immune response, there remains much to learn about qualitative and quantitative aspects of the human host response to vaccination. To stimulate discussion and identify opportunities for collaborative ways to advance the field of vaccine biomarkers, A Next Generation Vaccine Biomarker workshop was held in Ottawa. The two day workshop, sponsored by the National Research Council Canada, Canadian Institutes of Health Research, Public Health Agency of Canada, Pfizer, and Medicago, brought together stakeholders from Canadian and international industry, government and academia. The workshop was grouped in themes, covering vaccine biomarker challenges in the pre-clinical and clinical spaces, veterinary vaccines, regulatory challenges, and development of biomarkers for adjuvants and cancer vaccines. The use of case studies allowed participants to identify the needs and gaps requiring innovation. The workshop concluded with a discussion on opportunities for vaccine biomarker discovery, the Canadian context, and approaches for moving forward. This article provides a synopsis of these discussions and identifies steps forward for advancing vaccine biomarker research in Canada. PMID:26383909

Synthetic Influenza vaccine (FLU-v) stimulates cell mediated immunity in a double-blind, randomised, placebo-controlled Phase I trial.

PubMed

Pleguezuelos, Olga; Robinson, Stuart; Stoloff, Gregory A; Caparrós-Wanderley, Wilson

2012-06-29

Current Influenza vaccines elicit antibody mediated prophylactic immunity targeted to viral capsid antigens. Despite their global use these vaccines must be administered yearly to the population, cannot be manufactured until the circulating viral strain(s) have been identified and have limited efficacy. A need remains for Influenza vaccines addressing these issues and here we report the results of a Phase Ib trial of a novel synthetic Influenza vaccine (FLU-v) targeting T cell responses to NP, M1 and M2. Forty-eight healthy males aged 18-40 were recruited for this single-centre, randomised, double blind study. Volunteers received one single low (250 μg) or high (500 μg) dose of FLU-v, either alone or adjuvanted. Safety, tolerability and basic immunogenicity (IgG and IFN-γ responses) parameters were assessed pre-vaccination and for 21 days post-vaccination. FLU-v was found to be safe and well tolerated with no vaccine associated severe adverse events. Dose-dependent IFN-γ responses >2-fold the pre-vaccination level were detected in 80% and 100% of volunteers receiving, respectively, the low and high dose adjuvanted FLU-v formulations. No formulation tested induced any significant FLU-v antibody response. FLU-v is safe and induces a vaccine-specific cellular immunity. Cellular immune responses are historically known to control and mitigate infection and illness during natural infection. Copyright © 2012 Elsevier Ltd. All rights reserved.

Polymorphism in liver-stage malaria vaccine candidate proteins: immune evasion and implications for vaccine design.

PubMed

Flanagan, Katie L; Wilson, Kirsty L; Plebanski, Magdalena

2016-01-01

The pre-erythrocytic stage of infection by malaria parasites represents a key target for vaccines that aim to eradicate malaria. Two important broad immune evasion strategies that can interfere with vaccine efficacy include the induction of dendritic cell (DC) dysfunction and regulatory T cells (Tregs) by blood-stage malaria parasites, leading to inefficient priming of T cells targeting liver-stage infections. The parasite also uses 'surgical strike' strategies, whereby polymorphism in pre-erythrocytic antigens can interfere with host immunity. Specifically, we review how even single amino acid changes in T cell epitopes can lead to loss of binding to major histocompatibility complex (MHC), lack of cross-reactivity, or antagonism and immune interference, where simultaneous or sequential stimulation with related variants of the same T cell epitope can cause T cell anergy or the conversion of effector to immunosuppressive T cell phenotypes.

Aluminum adjuvants of vaccines injected into the muscle: Normal fate, pathology and associated disease.

PubMed

Gherardi, R K; Aouizerate, J; Cadusseau, J; Yara, S; Authier, F J

2016-06-01

Aluminum oxyhydroxide (Alhydrogel(®)) is a nano-crystalline compound forming aggregates that has been introduced in vaccine for its immunologic adjuvant effect in 1926. It is the most commonly used adjuvant in human and veterinary vaccines but mechanisms by which it stimulates immune responses remain ill-defined. Although generally well tolerated on the short term, it has been suspected to occasionally cause delayed neurologic problems in susceptible individuals. In particular, the long-term persistence of aluminic granuloma also termed macrophagic myofasciitis is associated with chronic arthromyalgias and fatigue and cognitive dysfunction. Safety concerns largely depend on the long biopersistence time inherent to this adjuvant, which may be related to its quick withdrawal from the interstitial fluid by avid cellular uptake; and the capacity of adjuvant particles to migrate and slowly accumulate in lymphoid organs and the brain, a phenomenon documented in animal models and resulting from MCP1/CCL2-dependant translocation of adjuvant-loaded monocyte-lineage cells (Trojan horse phenomenon). These novel insights strongly suggest that serious re-evaluation of long-term aluminum adjuvant phamacokinetics and safety should be carried out. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Motivational and contextual determinants of HPV-vaccination uptake: A longitudinal study among mothers of girls invited for the HPV-vaccination.

PubMed

Pot, Mirjam; van Keulen, Hilde M; Ruiter, Robert A C; Eekhout, Iris; Mollema, Liesbeth; Paulussen, Theo W G M

2017-07-01

In the Netherlands, HPV-vaccination uptake among 12-year-old girls remains to be lower (61% in 2016) than expected. The present study is about 1) replicating the extent to which social-psychological determinants found in earlier cross-sectional studies explain HPV-vaccination intention, and 2) testing whether HPV-vaccination intention, as well as other social-psychological determinants, are good predictors of future HPV-vaccination uptake in a longitudinal design. A random sample of mothers of girls invited for the vaccination in 2015 was drawn from the Dutch vaccination register (Praeventis) (N=36,000) and from three online panels (N=2483). Two months prior to the vaccination of girls, their mothers were requested to complete a web-based questionnaire by letter (Praeventis sample) or by e-mail (panel samples). HPV-vaccination uptake was derived from Praeventis. Backward linear and logistic regression analyses were conducted to examine most dominant predictors of HPV-vaccination intention and uptake, respectively. The total sample used for data analyses consisted of 8062 mothers. Response rates were 18% for the Praeventis sample and 47% for the panel samples. HPV-vaccination intention was best explained by attitude, beliefs, subjective norms, habit, and perceived relative effectiveness of the vaccination; they explained 83% of the variance in HPV-vaccination intention. Intention appeared to be the only stable predictor of HPV-vaccination uptake and explained 43% of the variance in HPV-vaccination uptake. These results confirm what was found by earlier cross-sectional studies, and provide strong leads for selecting relevant targets in the planning of future communication strategies aiming to improve HPV-vaccination uptake. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Vaccines to combat river blindness: expression, selection and formulation of vaccines against infection with Onchocerca volvulus in a mouse model.

PubMed

Hess, Jessica A; Zhan, Bin; Bonne-Année, Sandra; Deckman, Jessica M; Bottazzi, Maria Elena; Hotez, Peter J; Klei, Thomas R; Lustigman, Sara; Abraham, David

2014-08-01

Human onchocerciasis is a neglected tropical disease caused by Onchocerca volvulus and an important cause of blindness and chronic disability in the developing world. Although mass drug administration of ivermectin has had a profound effect on control of the disease, additional tools are critically needed including the need for a vaccine against onchocerciasis. The objectives of the present study were to: (i) select antigens with known vaccine pedigrees as components of a vaccine; (ii) produce the selected vaccine antigens under controlled conditions, using two expression systems and in one laboratory and (iii) evaluate their vaccine efficacy using a single immunisation protocol in mice. In addition, we tested the hypothesis that joining protective antigens as a fusion protein or in combination, into a multivalent vaccine, would improve the ability of the vaccine to induce protective immunity. Out of eight vaccine candidates tested in this study, Ov-103, Ov-RAL-2 and Ov-CPI-2M were shown to reproducibly induce protective immunity when administered individually, as fusion proteins or in combination. Although there was no increase in the level of protective immunity induced by combining the antigens into one vaccine, these antigens remain strong candidates for inclusion in a vaccine to control onchocerciasis in humans. Copyright © 2014 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

A Caprine Herpesvirus 1 Vaccine Adjuvanted with MF59™ Protects against Vaginal Infection and Interferes with the Establishment of Latency in Goats

PubMed Central

Marinaro, Mariarosaria; Rezza, Giovanni; Del Giudice, Giuseppe; Colao, Valeriana; Tarsitano, Elvira; Camero, Michele; Losurdo, Michele; Buonavoglia, Canio; Tempesta, Maria

2012-01-01

The immunogenicity and the efficacy of a beta-propiolactone-inactivated caprine herpesvirus 1 (CpHV-1) vaccine adjuvanted with MF59™ were tested in goats. Following two subcutaneous immunizations, goats developed high titers of CpHV-1-specific serum and vaginal IgG and high serum virus neutralization (VN) titers. Peripheral blood mononuclear cells (PBMC) stimulated in vitro with inactivated CpHV-1 produced high levels of soluble IFN-gamma and exhibited high frequencies of IFN-gamma producing cells while soluble IL-4 was undetectable. On the other hand, control goats receiving the inactivated CpHV-1 vaccine without adjuvant produced only low serum antibody responses. A vaginal challenge with virulent CpHV-1 was performed in all vaccinated goats and in naïve goats to assess the efficacy of the two vaccines. Vaginal disease was not detected in goats vaccinated with inactivated CpHV-1 plus MF59™ and these animals had undetectable levels of infectious challenge virus in their vaginal washes. Goats vaccinated with inactivated CpHV-1 in the absence of adjuvant exhibited a less severe disease when compared to naïve goats but shed titers of challenge virus that were similar to those of naïve goats. Detection and quantitation of latent CpHV-1 DNA in sacral ganglia in challenged goats revealed that the inactivated CpHV-1 plus MF59™ vaccine was able to significantly reduce the latent viral load when compared either to the naïve goats or to the goats vaccinated with inactivated CpHV-1 in the absence of adjuvant. Thus, a vaccine composed of inactivated CpHV-1 plus MF59™ as adjuvant was strongly immunogenic and induced effective immunity against vaginal CpHV-1 infection in goats. PMID:22511971

Anti-melanoma vaccines engineered to simultaneously modulate cytokine priming and silence PD-L1 characterized using ex vivo myeloid-derived suppressor cells as a readout of therapeutic efficacy.

PubMed

Liechtenstein, Therese; Perez-Janices, Noemi; Blanco-Luquin, Idoia; Goyvaerts, Cleo; Schwarze, Julia; Dufait, Ines; Lanna, Alessio; Ridder, Mark De; Guerrero-Setas, David; Breckpot, Karine; Escors, David

Efficacious antitumor vaccines strongly stimulate cancer-specific effector T cells and counteract the activity of tumor-infiltrating immunosuppressive cells. We hypothesised that combining cytokine expression with silencing programmed cell death ligand 1 (PD-L1) could potentiate anticancer immune responses of lentivector vaccines. Thus, we engineered a collection of lentivectors that simultaneously co-expressed an antigen, a PD-L1-silencing shRNA, and various T cell-polarising cytokines, including interferon γ (IFNγ), transforming growth factor β (TGFβ) or interleukins (IL12, IL15, IL23, IL17A, IL6, IL10, IL4). In a syngeneic B16F0 melanoma model and using tyrosinase related protein 1 (TRP1) as a vaccine antigen, we found that simultaneous delivery of IL12 and a PD-L1-silencing shRNA was the only combination that exhibited therapeutically relevant anti-melanoma activities. Mechanistically, we found that delivery of the PD-L1 silencing construct boosted T cell numbers, inhibited in vivo tumor growth and strongly cooperated with IL12 cytokine priming and antitumor activities. Finally, we tested the capacities of our vaccines to counteract tumor-infiltrating myeloid-derived suppressor cell (MDSC) activities ex vivo . Interestingly, the lentivector co-expressing IL12 and the PD-L1 silencing shRNA was the only one that counteracted MDSC suppressive activities, potentially underlying the observed anti-melanoma therapeutic benefit. We conclude that (1) evaluation of vaccines in healthy mice has no significant predictive value for the selection of anticancer treatments; (2) B16 cells expressing xenoantigens as a tumor model are of limited value; and (3) vaccines which inhibit the suppressive effect of MDSC on T cells in our ex vivo assay show promising and relevant antitumor activities.

Anti-melanoma vaccines engineered to simultaneously modulate cytokine priming and silence PD-L1 characterized using ex vivo myeloid-derived suppressor cells as a readout of therapeutic efficacy

PubMed Central

Liechtenstein, Therese; Perez-Janices, Noemi; Blanco-Luquin, Idoia; Goyvaerts, Cleo; Schwarze, Julia; Dufait, Ines; Lanna, Alessio; Ridder, Mark De; Guerrero-Setas, David; Breckpot, Karine; Escors, David

2014-01-01

Efficacious antitumor vaccines strongly stimulate cancer-specific effector T cells and counteract the activity of tumor-infiltrating immunosuppressive cells. We hypothesised that combining cytokine expression with silencing programmed cell death ligand 1 (PD-L1) could potentiate anticancer immune responses of lentivector vaccines. Thus, we engineered a collection of lentivectors that simultaneously co-expressed an antigen, a PD-L1-silencing shRNA, and various T cell-polarising cytokines, including interferon γ (IFNγ), transforming growth factor β (TGFβ) or interleukins (IL12, IL15, IL23, IL17A, IL6, IL10, IL4). In a syngeneic B16F0 melanoma model and using tyrosinase related protein 1 (TRP1) as a vaccine antigen, we found that simultaneous delivery of IL12 and a PD-L1-silencing shRNA was the only combination that exhibited therapeutically relevant anti-melanoma activities. Mechanistically, we found that delivery of the PD-L1 silencing construct boosted T cell numbers, inhibited in vivo tumor growth and strongly cooperated with IL12 cytokine priming and antitumor activities. Finally, we tested the capacities of our vaccines to counteract tumor-infiltrating myeloid-derived suppressor cell (MDSC) activities ex vivo. Interestingly, the lentivector co-expressing IL12 and the PD-L1 silencing shRNA was the only one that counteracted MDSC suppressive activities, potentially underlying the observed anti-melanoma therapeutic benefit. We conclude that (1) evaluation of vaccines in healthy mice has no significant predictive value for the selection of anticancer treatments; (2) B16 cells expressing xenoantigens as a tumor model are of limited value; and (3) vaccines which inhibit the suppressive effect of MDSC on T cells in our ex vivo assay show promising and relevant antitumor activities. PMID:25954597

Current Efforts and Future Prospects in the Development of Live Mycobacteria as Vaccines

PubMed Central

Porcelli, Steven A.; Ng, Tony W.; Saavedra-Avila, Noemi A; Kennedy, Steven C.; Carreno, Leandro J.

2016-01-01

Summary The development of more effective vaccines against Mycobacterium tuberculosis (Mtb) remains a major goal in the effort to reduce the enormous global burden of disease caused by this pathogen. Whole-cell vaccines based on live mycobacteria with attenuated virulence represent an appealing approach, providing broad antigen exposure and intrinsic adjuvant properties to prime durable immune responses. However, designing vaccine strains with an optimal balance between attenuation and immunogenicity has proven to be extremely challenging. Recent basic and clinical research efforts have broadened our understanding of Mtb pathogenesis and created numerous new vaccine candidates that are designed to overcome different aspects of immune evasion by Mtb. In this review, we provide an overview of current efforts to create improved vaccines against tuberculosis based on modifications of live attenuated mycobacteria. In addition, we discuss the use of such vaccine strains as vectors for stimulating protective immunity against other infectious diseases and cancers. PMID:26366616

Elevated Immune Response Among Children 4 Years of Age With Pronounced Local Adverse Events After the Fifth Diphtheria, Tetanus, Acellular Pertussis Vaccination.

PubMed

van der Lee, Saskia; Kemmeren, Jeanet M; de Rond, Lia G H; Öztürk, Kemal; Westerhof, Anneke; de Melker, Hester E; Sanders, Elisabeth A M; Berbers, Guy A M; van der Maas, Nicoline A T; Rümke, Hans C; Buisman, Anne-Marie

2017-09-01

In the Netherlands, acellular pertussis vaccines replaced the more reactogenic whole-cell pertussis vaccines. This replacement in the primary immunization schedule of infants coincided with a significant increase in pronounced local adverse events (AEs) in 4 years old children shortly after the administration of a fifth diphtheria, tetanus, acellular pertussis and inactivated polio (DTaP-IPV) vaccine. The objective of this study was to investigate possible differences in vaccine antigen-specific immune responses between children with and without a pronounced local AE after the fifth DTaP-IPV vaccination. Blood was sampled in 2 groups of 4-year-olds: a case group reporting pronounced local swelling and/or erythema up to extensive limb swelling at the injection site (n = 30) and a control group (n = 30). Peripheral blood mononuclear cells were stimulated with individual vaccine antigens. Plasma antigen-specific IgG, IgG subclass and total IgE concentrations and T-cell cytokine [interferon-gamma, interleukin (IL)-13, IL-17 and IL-10] production by stimulated peripheral blood mononuclear cells were determined by multiplex bead-based fluorescent multiplex immunoassays. In children with AEs, significantly higher total IgE and vaccine antigen-specific IgG and IgG4 responses as well as levels of the T-helper 2 (Th2) cytokine IL-13 were found after pertussis, tetanus and diphtheria stimulation compared with controls. Children with pronounced local reactions show higher humoral and cellular immune responses. Acellular vaccines are known to skew toward more Th2 responses. The pronounced local AEs may be associated with more Th2 skewing after the fifth DTaP-IPV vaccination, but other biologic factors may also impact the occurrence of these pronounced local reactions.

Localized mucosal response to intranasal live attenuated influenza vaccine in adults.

PubMed

Barría, Maria Ines; Garrido, Jose Luis; Stein, Cheryl; Scher, Erica; Ge, Yongchao; Engel, Stephanie M; Kraus, Thomas A; Banach, David; Moran, Thomas M

2013-01-01

Influenza virus infection is a major public health burden worldwide. Available vaccines include the inactivated intramuscular trivalent vaccine and, more recently, an intranasal live attenuated influenza vaccine (LAIV). The measure of successful vaccination with the inactivated vaccine is a systemic rise in immunoglobulin G (IgG) level, but for the LAIV no such correlate has been established. Seventy-nine subjects were given the LAIV FluMist. Blood was collected prior to vaccination and 3 days and 30 days after vaccination. Nasal wash was collected 3 days and 30 days after vaccination. Responses were measured systemically and in mucosal secretions for cytokines, cell activation profiles, and antibody responses. Only 9% of subjects who received LAIV seroconverted, while 33% of patients developed at least a 2-fold increase in influenza virus-specific immunoglobulin A (IgA) antibodies in nasal wash. LAIV induced a localized inflammation, as suggested by increased expression of interferon-response genes in mucosal RNA and increased granulocyte colony-stimulating factor (G-CSF) and IP-10 in nasal wash. Interestingly, patients who seroconverted had significantly lower serum levels of G-CSF before vaccination. Protection by LAIV is likely provided through mucosal IgA and not by increases in systemic IgG. LAIV induces local inflammation. Seroconversion is achieved in a small fraction of subjects with a lower serum G-CSF level.

Overview of dendritic cell-based vaccine development for leishmaniasis.

PubMed

Bagirova, M; Allahverdiyev, A M; Abamor, E S; Ullah, I; Cosar, G; Aydogdu, M; Senturk, H; Ergenoglu, B

2016-11-01

Leishmaniasis is one of the most serious vector-borne diseases in the world and is distributed over 98 countries. It is estimated that 350 million people are at risk for leishmaniasis. There are three different generation of vaccines that have been developed to provide immunity and protection against leishmaniasis. However, their use has been limited due to undesired side effects. These vaccines have also failed to provide effective and reliable protection and, as such, currently, there is no safe and effective vaccine for leishmaniasis. Dendritic cells (DCs) are a unique population of cells that come from bone marrow and become specialized to take up, process and present antigens to helper T cells in a mechanism similar to macrophages. By considering these significant features, DCs stimulated with different kinds of Leishmania antigens have been used in recent vaccine studies for leishmaniasis with promising results so far. In this review, we aim to review and combine the latest studies about this issue after defining potential problems in vaccine development for leishmaniasis and considering the importance of DCs in the immunopathogenesis of the disease. © 2016 John Wiley & Sons Ltd.

Against Strong Ethical Parity: Situated Cognition Theses and Transcranial Brain Stimulation

PubMed Central

Heinrichs, Jan-Hendrik

2017-01-01

According to a prominent suggestion in the ethics of transcranial neurostimulation the effects of such devices can be treated as ethically on par with established, pre-neurotechnological alterations of the mind. This parity allegedly is supported by situated cognition theories showing how external devices can be part of a cognitive system. This article will evaluate this suggestion. It will reject the claim, that situated cognition theories support ethical parity. It will however point out another reason, why external carriers or modifications of the mental might come to be considered ethically on par with internal carriers. Section “Why Could There Be Ethical Parity between Neural Tissue and External Tools?” presents the ethical parity theses between external and internal carriers of the mind as well as neurotechnological alterations and established alterations. Section “Extended, Embodied, Embedded: Situated Cognition as a Relational Thesis” will elaborate the different situated cognition approaches and their relevance for ethics. It will evaluate, whether transcranial stimulation technologies are plausible candidates for situated cognition theses. Section “On the Ethical Relevance of Situated Cognition Theses” will discuss criteria for evaluating whether a cognitive tool is deeply embedded with a cognitive system and apply these criteria to transcranial brain stimulation technologies. Finally it will discuss the role diverse versions of situated cognition theory can play in the ethics of altering mental states, especially the ethics of transcranial brain stimulation technologies. PMID:28443008

Herpes Zoster Caused by Vaccine-Strain Varicella Zoster Virus in an Immunocompetent Recipient of Zoster Vaccine

PubMed Central

Tseng, Hung Fu; Schmid, D. Scott; Harpaz, Rafael; LaRussa, Philip; Jensen, Nancy J.; Rivailler, Pierre; Radford, Kay; Folster, Jennifer; Jacobsen, Steven J.

2014-01-01

We report the first laboratory-documented case of herpes zoster caused by the attenuated varicella zoster virus (VZV) contained in Zostavax in a 68-year-old immunocompetent adult with strong evidence of prior wild-type VZV infection. The complete genome sequence of the isolate revealed that the strain carried 15 of 42 (36%) recognized varicella vaccine–associated single-nucleotide polymorphisms, including all 5 of the fixed vaccine markers present in nearly all of the strains in the vaccine. The case of herpes zoster was relatively mild and resolved without complications. PMID:24470276

The Final (Oral Ebola) Vaccine Trial on Captive Chimpanzees?

PubMed Central

Walsh, Peter D.; Kurup, Drishya; Hasselschwert, Dana L.; Wirblich, Christoph; Goetzmann, Jason E.; Schnell, Matthias J.

2017-01-01

Could new oral vaccine technologies protect endangered wildlife against a rising tide of infectious disease? We used captive chimpanzees to test oral delivery of a rabies virus (RABV) vectored vaccine against Ebola virus (EBOV), a major threat to wild chimpanzees and gorillas. EBOV GP and RABV GP-specific antibody titers increased exponentially during the trial, with rates of increase for six orally vaccinated chimpanzees very similar to four intramuscularly vaccinated controls. Chimpanzee sera also showed robust neutralizing activity against RABV and pseudo-typed EBOV. Vaccination did not induce serious health complications. Blood chemistry, hematologic, and body mass correlates of psychological stress suggested that, although sedation induced acute stress, experimental housing conditions did not induce traumatic levels of chronic stress. Acute behavioral and physiological responses to sedation were strongly correlated with immune responses to vaccination. These results suggest that oral vaccination holds great promise as a tool for the conservation of apes and other endangered tropical wildlife. They also imply that vaccine and drug trials on other captive species need to better account for the effects of stress on immune response. PMID:28277549

Relationship between maternal experiences and adolescent HPV vaccination.

PubMed

Berenson, Abbey B; Brown, V Gnaukita; Fuchs, Erika L; Hirth, Jacqueline M; Chang, Mihyun

2017-09-02

The human papillomavirus (HPV) vaccine has been available for over a decade but its uptake rate is still low. To explore the relationship between the HPV vaccination status of a child and their mother's beliefs, behaviors and knowledge, we surveyed 1497 women with at least one child aged 9-17 y between September 2011 and November 2015. Physician recommendation was the most important factor associated with reported child vaccination status. Mothers who reported receiving a provider recommendation for the HPV vaccine were 32 times more likely to have a child who had been vaccinated compared with mothers who did not report provider recommendation (aOR) = 32.17; 95% CI: 21.77, 47.54). Knowing someone who had received the vaccine was also strongly associated with vaccination uptake (59% vs 12%, p < .001). Additionally, prior HPV diagnosis (aOR = 1.91; 95% CI: 1.18, 3.10) and knowing someone with cervical cancer (aOR = 1.38; 95% CI: 1.01, 1.89) were associated with child vaccination status. Mothers who perceived moderate to high risk for their child contracting HPV or developing genital warts or cervical cancer were more likely to report that their daughters (but not their sons) had been vaccinated.

Adjuvanted pandemic influenza vaccine: variation of emulsion components affects stability, antigen structure, and vaccine efficacy

PubMed Central

Fox, Christopher B.; Barnes V, Lucien; Evers, Tara; Chesko, James D.; Vedvick, Thomas S.; Coler, Rhea N.; Reed, Steven G.; Baldwin, Susan L.

2012-01-01

Please cite this paper as: Fox et al. (2012) Adjuvanted pandemic influenza vaccine: variation of emulsion components affects stability, antigen structure, and vaccine efficacy. Influenza and Other Respiratory Viruses DOI: 10.1111/irv.12031. Abstract Background  Adjuvant formulations are critical components of modern vaccines based on recombinant proteins, which are often poorly immunogenic without additional immune stimulants. Oil‐in‐water emulsions comprise an advanced class of vaccine adjuvants that are components of approved seasonal and pandemic influenza vaccines. However, few reports have been published that systematically evaluate the in vitro stability and in vivo adjuvant effects of different emulsion components. Objectives  To evaluate distinct classes of surfactants, oils, and excipients, for their effects on emulsion particle size stability, antigen structural interactions, and in vivo activity when formulated with a recombinant H5N1 antigen. Methods  Emulsions were manufactured by high pressure homogenization and characterized alone or in the presence of vaccine antigen by dynamic light scattering, zeta potential, viscosity, pH, hemolytic activity, electron microscopy, fluorescence spectroscopy, and SDS‐PAGE. In vivo vaccine activity in the murine model was characterized by measuring antibody titers, antibody‐secreting plasma cells, hemagglutination inhibition titers, and cytokine production. Results  We demonstrate that surfactant class and presence of additional excipients are not critical for biological activity, whereas oil structure is crucial. Moreover, we report that simplified two‐component emulsions appear more stable by particle size than more complex formulations.Finally, differences in antigen structural interactions with the various emulsions do not appear to correlate with in vivo activity. Conclusions  Oil‐in‐water emulsions can significantly enhance antibody and cellular immune responses to a pandemic influenza

The Live Attenuated Cholera Vaccine CVD 103-HgR Primes Responses to the Toxin-Coregulated Pilus Antigen TcpA in Subjects Challenged with Wild-Type Vibrio cholerae.

PubMed

Mayo-Smith, Leslie M; Simon, Jakub K; Chen, Wilbur H; Haney, Douglas; Lock, Michael; Lyon, Caroline E; Calderwood, Stephen B; Kirkpatrick, Beth D; Cohen, Mitchell; Levine, Myron M; Gurwith, Marc; Harris, Jason B

2017-01-01

One potential advantage of live attenuated bacterial vaccines is the ability to stimulate responses to antigens which are only expressed during the course of infection. To determine whether the live attenuated cholera vaccine CVD 103-HgR (Vaxchora) results in antibody responses to the in vivo-induced toxin-coregulated pilus antigen TcpA, we measured IgA and IgG responses to Vibrio cholerae O1 El Tor TcpA in a subset of participants in a recently reported experimental challenge study. Participants were challenged with V. cholerae O1 El Tor Inaba N16961 either 10 days or 90 days after receiving the vaccine or a placebo. Neither vaccination nor experimental infection with V. cholerae alone resulted in a robust TcpA IgG or IgA response, but each did elicit a strong response to cholera toxin. However, compared to placebo recipients, vaccinees had a marked increase in IgG TcpA antibodies following the 90-day challenge, suggesting that vaccination with CVD 103-HgR resulted in priming for a subsequent response to TcpA. No such difference between vaccine and placebo recipients was observed for volunteers challenged 10 days after vaccination, indicating that this was insufficient time for vaccine-induced priming of the TcpA response. The priming of the response to TcpA and potentially other antigens expressed in vivo by attenuated V. cholerae may have relevance to the maintenance of immunity in areas where cholera is endemic. Copyright © 2017 American Society for Microbiology.

Strengthening vaccination policies in Latin America: an evidence-based approach.

PubMed

Tapia-Conyer, Roberto; Betancourt-Cravioto, Miguel; Saucedo-Martínez, Rodrigo; Motta-Murguía, Lourdes; Gallardo-Rincón, Héctor

2013-08-20

Despite many successes in the region, Latin American vaccination policies have significant shortcomings, and further work is needed to maintain progress and prepare for the introduction of newly available vaccines. In order to address the challenges facing Latin America, the Commission for the Future of Vaccines in Latin America (COFVAL) has made recommendations for strengthening evidence-based policy-making and reducing regional inequalities in immunisation. We have conducted a comprehensive literature review to assess the feasibility of these recommendations. Standardisation of performance indicators for disease burden, vaccine coverage, epidemiological surveillance and national health resourcing can ensure comparability of the data used to assess vaccination programmes, allowing deeper analysis of how best to provide services. Regional vaccination reference schemes, as used in Europe, can be used to develop best practice models for vaccine introduction and scheduling. Successful models exist for the continuous training of vaccination providers and decision-makers, with a new Latin American diploma aiming to contribute to the successful implementation of vaccination programmes. Permanent, independent vaccine advisory committees, based on the US Advisory Committee on Immunization Practices (ACIP), could facilitate the uptake of new vaccines and support evidence-based decision-making in the administration of national immunisation programmes. Innovative financing mechanisms for the purchase of new vaccines, such as advance market commitments and cost front-loading, have shown potential for improving vaccine coverage. A common regulatory framework for vaccine approval is needed to accelerate delivery and pool human, technological and scientific resources in the region. Finally, public-private partnerships between industry, government, academia and non-profit sectors could provide new investment to stimulate vaccine development in the region, reducing prices in the

History of the restoration of adenovirus type 4 and type 7 vaccine, live oral (Adenovirus Vaccine) in the context of the Department of Defense acquisition system.

PubMed

Hoke, Charles H; Snyder, Clifford E

2013-03-15

Respiratory pathogens cause morbidity and mortality in US military basic trainees. Following the influenza pandemic of 1918, and stimulated by WWII, the need to protect military personnel against epidemic respiratory disease was evident. Over several decades, the US military elucidated etiologies of acute respiratory diseases and invented and deployed vaccines to prevent disease caused by influenza, meningococcus, and adenoviruses. In 1994, the Adenovirus Vaccine manufacturer stopped its production. By 1999, supplies were exhausted and adenovirus-associated disease, especially serotype 4-associated febrile respiratory illness, returned to basic training installations. Advisory bodies persuaded Department of Defense leaders to initiate restoration of Adenovirus Vaccine. In 2011, after 10 years of effort by government and contractor personnel and at a cost of about $100 million, the Adenovirus Vaccine was restored to use at all military basic training installations. Disease and adenovirus serotype 4 isolation rates have fallen dramatically since vaccinations resumed in October 2011 and remain very low. Mindful of the adage that "The more successful a vaccine is, the more quickly the need for it will be forgotten.", sustainment of the supply of the Adenovirus Vaccine may be a challenge, and careful management will be required for such sustainment. Copyright © 2012 Elsevier Ltd. All rights reserved.

Strategies to Improve Vaccine Efficacy against Tuberculosis by Targeting Innate Immunity