Adjuvant-dependent innate and adaptive immune signatures of risk of SIVmac251 acquisition.

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Vaccari, Monica; Gordon, Shari N; Fourati, Slim; Schifanella, Luca; Liyanage, Namal P M; Cameron, Mark; Keele, Brandon F; Shen, Xiaoying; Tomaras, Georgia D; Billings, Erik; Rao, Mangala; Chung, Amy W; Dowell, Karen G; Bailey-Kellogg, Chris; Brown, Eric P; Ackerman, Margaret E; Vargas-Inchaustegui, Diego A; Whitney, Stephen; Doster, Melvin N; Binello, Nicolo; Pegu, Poonam; Montefiori, David C; Foulds, Kathryn; Quinn, David S; Donaldson, Mitzi; Liang, Frank; Loré, Karin; Roederer, Mario; Koup, Richard A; McDermott, Adrian; Ma, Zhong-Min; Miller, Christopher J; Phan, Tran B; Forthal, Donald N; Blackburn, Matthew; Caccuri, Francesca; Bissa, Massimiliano; Ferrari, Guido; Kalyanaraman, Vaniambadi; Ferrari, Maria G; Thompson, DeVon; Robert-Guroff, Marjorie; Ratto-Kim, Silvia; Kim, Jerome H; Michael, Nelson L; Phogat, Sanjay; Barnett, Susan W; Tartaglia, Jim; Venzon, David; Stablein, Donald M; Alter, Galit; Sekaly, Rafick-Pierre; Franchini, Genoveffa

2016-07-01

A recombinant vaccine containing Aventis Pasteur's canarypox vector (ALVAC)-HIV and gp120 alum decreased the risk of HIV acquisition in the RV144 vaccine trial. The substitution of alum with the more immunogenic MF59 adjuvant is under consideration for the next efficacy human trial. We found here that an ALVAC-simian immunodeficiency virus (SIV) and gp120 alum (ALVAC-SIV + gp120) equivalent vaccine, but not an ALVAC-SIV + gp120 MF59 vaccine, was efficacious in delaying the onset of SIVmac251 in rhesus macaques, despite the higher immunogenicity of the latter adjuvant. Vaccine efficacy was associated with alum-induced, but not with MF59-induced, envelope (Env)-dependent mucosal innate lymphoid cells (ILCs) that produce interleukin (IL)-17, as well as with mucosal IgG to the gp120 variable region 2 (V2) and the expression of 12 genes, ten of which are part of the RAS pathway. The association between RAS activation and vaccine efficacy was also observed in an independent efficacious SIV-vaccine approach. Whether RAS activation, mucosal ILCs and antibodies to V2 are also important hallmarks of HIV-vaccine efficacy in humans will require further studies.

The dog that did not bark: malaria vaccines without antibodies.

NARCIS (Netherlands)

Heppner, D.G.; Schwenk, R.J.; Arnot, D.; Sauerwein, R.W.; Luty, A.J.F.

2007-01-01

To date, the only pre-blood stage vaccine to confer protection against malaria in field trials elicits both antigen-specific antibody and T-cell responses. Recent clinical trials of new heterologous prime-boost malaria vaccine regimens using DNA, fowlpox or MVA, have chiefly elicited T-cell

A Multiplex Microsphere-Based Immunoassay Increases the Sensitivity of SIV-Specific Antibody Detection in Serum Samples and Mucosal Specimens Collected from Rhesus Macaques Infected with SIVmac239.

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Powell, Rebecca L R; Ouellette, Ian; Lindsay, Ross W; Parks, Christopher L; King, C Richter; McDermott, Adrian B; Morrow, Gavin

2013-06-01

Results from recent HIV-1 vaccine studies have indicated that high serum antibody (Ab) titers may not be necessary for Ab-mediated protection, and that Abs localized to mucosal sites might be critical for preventing infection. Enzyme-linked immunosorbent assay (ELISA) has been used for decades as the gold standard for Ab measurement, though recently, highly sensitive microsphere-based assays have become available, with potential utility for improved detection of Abs. In this study, we assessed the Bio-Plex(®) Suspension Array System for the detection of simian immunodeficiency virus (SIV)-specific Abs in rhesus macaques (RMs) chronically infected with SIV, whose serum or mucosal SIV-specific Ab titers were negative by ELISA. We developed a SIVmac239-specific 4-plex bead array for the simultaneous detection of Abs binding to Env, Gag, Pol, and Nef. The 4-plex assay was used to quantify SIV-specific serum IgG and rectal swab IgA titers from control (SIV-naive) and SIVmac239-infected RMs. The Bio-Plex assay specifically detected anti-SIV Abs in specimens from SIV-infected animals for all four analytes when compared to SIV-naive control samples (p≤0.04). Furthermore, in 70% of Env and 79% of Gag ELISA-negative serum samples, specific Ab was detected using the Bio-Plex assay. Similarly, 71% of Env and 48% of Gag ELISA-negative rectal swab samples were identified as positive using the Bio-Plex assay. Importantly, assay specificity (i.e., probability of true positives) was comparable to ELISA (94%-100%). The results reported here indicate that microsphere-based methods provide a substantial improvement over ELISA for the detection of Ab responses, aid in detecting specific Abs when analyzing samples containing low levels of Abs, such as during the early stages of a vaccine trial, and may be valuable in attempts to link protective efficacy of vaccines with induced Ab responses.

Concurrent Fowlpox and Candidiasis Diseases in Backyard Chickens with Unusual Pox Lesions in the Bursa of Fabricius.

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Ogasawara, Fusae; Yamamoto, Yu; Sato, Yasuo; Fukunari, Kazuhiro; Murata, Ken-Ichi; Yaegashi, Gakuji; Goto, Makiko; Murakami, Ryukoh

2016-09-01

Concurrent fowlpox and candidiasis diseases occurred in a backyard chicken flock. Four deceased chickens (one Nagoya breed and three white silkie chickens) were examined for diagnosis. At necropsy, white curd-like plaques were observed in the crop. Fungal elements that stained positive for Candida albicans with immunohistochemistry were distributed throughout the tongue, choanal mucosa, esophagus, and crop. Typical fowlpox lesions, composed of proliferating epithelial cells with ballooning degeneration and viral intracytoplasmic inclusions, were observed in the conjunctiva, nasal mucosa, and skin around the cloaca. Interestingly, hyperplastic interfollicular epithelium with rare virus inclusions was observed in the bursa of Fabricius (BF). Some bursal follicles were replaced by proliferating epithelial cells. These proliferating cells immunohistochemically stained positive for cytokeratin. PCR and subsequent genetic sequencing detected the C. albicans gene in the crop, and fowlpox virus genes in the BF. These results indicate that this outbreak was a rare presentation of fowlpox in spontaneously infected chickens, with unusual pox lesions in the BF.

A prime/boost strategy by DNA/fowlpox recombinants expressing a mutant E7 protein for the immunotherapy of HPV-associated cancers.

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Radaelli, Antonia; De Giuli Morghen, Carlo; Zanotto, Carlo; Pacchioni, Sole; Bissa, Massimiliano; Franconi, Rosella; Massa, Silvia; Paolini, Francesca; Muller, Antonio; Venuti, Aldo

2012-12-01

Development of effective therapeutic vaccines against human papilloma virus (HPV) infections remains a priority, considering the high number of new cases of cervical cancer each year by high-risk HPVs, in particular by HPV-16. Vaccines expressing the E7 oncoprotein, which is detectable in all HPV-positive pre-cancerous and cancer cells, might clear already established tumors and support the treatment of HPV-related lesions. In this study, DNA or fowlpox virus recombinants expressing the harmless variant E7GGG of the HPV-16 E7 oncoprotein (DNA(E7GGG) and FP(E7GGG)) were generated. Two immunization regimens were tested in a pre-clinical mouse model by homologous (FP/FP) or heterologous (DNA/FP) prime-boost protocols to evaluate the immune response and therapeutic efficacy of the proposed HPV-16 vaccine. Low levels of anti-E7-specific antibodies were elicited after immunization, and in vivo experiments resulted in a higher number of tumor-free mice after the heterologous immunization. These results establish a preliminary indication for therapy of HPV-related tumors by the combined use of DNA and avipox recombinants, which might represent safer immunogens than vaccinia-based vaccines. Copyright © 2012 Elsevier B.V. All rights reserved.

Rectal HSV-2 Infection May Increase Rectal SIV Acquisition Even in the Context of SIVΔnef Vaccination.

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Natalia Guerra-Pérez

Full Text Available Prevalent HSV-2 infection increases the risk of HIV acquisition both in men and women even in asymptomatic subjects. Understanding the impact of HSV-2 on the mucosal microenvironment may help to identify determinants of susceptibility to HIV. Vaginal HSV-2 infection increases the frequency of cells highly susceptible to HIV in the vaginal tissue of women and macaques and this correlates with increased susceptibility to vaginal SHIV infection in macaques. However, the effect of rectal HSV-2 infection on HIV acquisition remains understudied. We developed a model of rectal HSV-2 infection in macaques in combination with rectal SIVmac239Δnef (SIVΔnef vaccination and our results suggest that rectal HSV-2 infection may increase the susceptibility of macaques to rectal SIVmac239 wild-type (wt infection even in SIVΔnef-infected animals. Rectal SIVΔnef infection/vaccination protected 7 out of 7 SIVΔnef-infected macaques from SIVmac239wt rectal infection (vs 12 out of 16 SIVΔnef-negative macaques, while 1 out of 3 animals co-infected with SIVΔnef and HSV-2 acquired SIVmac239wt infection. HSV-2/SIVmac239wt co-infected animals had increased concentrations of inflammatory factors in their plasma and rectal fluids and a tendency toward higher acute SIVmac239wt plasma viral load. However, they had higher blood CD4 counts and reduced depletion of CCR5+ CD4+ T cells compared to SIVmac239wt-only infected animals. Thus, rectal HSV-2 infection generates a pro-inflammatory environment that may increase susceptibility to rectal SIV infection and may impact immunological and virological parameters during acute SIV infection. Studies with larger number of animals are needed to confirm these findings.

Comparative evaluation of oral and intranasal priming with replication-competent adenovirus 5 host range mutant (Ad5hr)-simian immunodeficiency virus (SIV) recombinant vaccines on immunogenicity and protective efficacy against SIV(mac251).

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Zhou, Qifeng; Hidajat, Rachmat; Peng, Bo; Venzon, David; Aldrich, M Kristine; Richardson, Ersell; Lee, Eun Mi; Kalyanaraman, V S; Grimes, George; Gómez-Román, V Raúl; Summers, L Ebonita; Malkevich, Nina; Robert-Guroff, Marjorie

2007-11-19

Oral, replication-competent Ad-HIV vaccines are advancing to human trials. Previous evaluation of protective efficacy in non-human primates has primarily followed upper respiratory tract administrations. Here we compared sequential oral (O/O) versus intranasal/oral (I/O) priming of rhesus macaques with Ad5 host range mutant-SIV recombinants expressing SIV env/rev, gag, and nef genes followed by boosting with SIV gp120 protein. Cellular immune responses in PBMC were stronger and more frequent after I/O administration. Both groups developed mucosal immunity, including memory cells in bronchial alveolar lavage, and gut-homing receptors on PBMC. Following intrarectal SIV(mac251) challenge, both groups exhibited equivalent, significant protection and robust post-challenge cellular immunity. Our results illustrate the promise of oral replication-competent Ad-recombinant vaccines. Pre-challenge PBMC ELISPOT and proliferative responses did not predict protection in the O/O group, highlighting the need for simple, non-invasive methods to reliably assess mucosal immunity.

Cytotoxic T-Lymphocyte Escape Does Not Always Explain the Transient Control of Simian Immunodeficiency Virus SIVmac239 Viremia in Adenovirus-Boosted and DNA-Primed Mamu-A*01-Positive Rhesus Macaques

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McDermott, Adrian B.; O'Connor, David H.; Fuenger, Sarah; Piaskowski, Shari; Martin, Sarah; Loffredo, John; Reynolds, Matthew; Reed, Jason; Furlott, Jessica; Jacoby, Timothy; Riek, Cara; Dodds, Elizabeth; Krebs, Kendall; Davies, Mary-Ellen; Schleif, William A.; Casimiro, Danilo R.; Shiver, John W.; Watkins, D. I.

2005-01-01

Adenovirus 5 (Ad5) vectors show promise as human immunodeficiency virus vaccine candidates. Indian rhesus macaques vaccinated with Ad5-gag controlled simian-human immunodeficiency virus SHIV89.6P viral replication in the absence of Env immunogens that might elicit humoral immunity. Here we immunized 15 macaques using either a homologous Ad5-gag/Ad5-gag (Ad5/Ad5) or a heterologous DNA-gag/Ad5-gag (DNA/Ad5) prime-boost regimen and challenged them with a high dose of simian immunodeficiency virus SIVmac239. Macaques vaccinated with the DNA/Ad5 regimen experienced a brief viral load nadir of less than 10,000 viral copies per ml blood plasma that was not seen in Mamu-A*01-negative DNA/Ad5 vaccinees, Mamu-A*01-positive Ad5/Ad5 vaccinees, or vaccine-naive controls. Interestingly, most of these animals were not durably protected from disease progression when challenged with SIVmac239. To investigate the reasons underlying this short-lived vaccine effect, we investigated breadth of the T-cell response, immunogenetic background, and viral escape from CD8+ lymphocytes that recognize immunodominant T-cell epitopes. We show that these animals do not mount unusually broad cellular immune response, nor do they express unusual major histocompatibility complex class I alleles. Viral recrudescence occurred in four of the five Mamu-A*01-positive vaccinated macaques. However, only a single animal in this group demonstrated viral escape in the immunodominant Gag181-189CM9 response. These results suggest that viral “breakthrough” in vaccinated animals and viral escape are not inextricably linked and underscore the need for additional research into the mechanisms of vaccine failure. PMID:16306626

Comparison of protection from homologous cell-free vs cell-associated SIV challenge afforded by inactivated whole SIV vaccines.

NARCIS (Netherlands)

J.L. Heeney (Jonathan); P. de Vries (Petra); R. Dubbes (Rob); W. Koornstra (Willem); H. Niphuis; P. ten Haaft (Peter); J. Boes (Jolande); M.E.M. Dings (Marlinda); B. Morein (Bror); A.D.M.E. Osterhaus (Albert)

1992-01-01

textabstractThis study attempted to determine if SIV vaccines could protect against challenge with peripheral blood mononuclear cells (PBMCs) from an SIV infected rhesus monkey. Mature Macaca mulatta were vaccinated four times with formalin inactivated SIVmac32H administered in MDP adjuvant (n = 8)

Development of the PANVAC-VF vaccine for pancreatic cancer.

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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.

A prime/boost strategy using DNA/fowlpox recombinants expressing the genetically attenuated E6 protein as a putative vaccine against HPV-16-associated cancers.

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Bissa, Massimiliano; Illiano, Elena; Pacchioni, Sole; Paolini, Francesca; Zanotto, Carlo; De Giuli Morghen, Carlo; Massa, Silvia; Franconi, Rosella; Radaelli, Antonia; Venuti, Aldo

2015-03-05

Considering the high number of new cases of cervical cancer each year that are caused by human papilloma viruses (HPVs), the development of an effective vaccine for prevention and therapy of HPV-associated cancers, and in particular against the high-risk HPV-16 genotype, remains a priority. Vaccines expressing the E6 and E7 proteins that are detectable in all HPV-positive pre-cancerous and cancer cells might support the treatment of HPV-related lesions and clear already established tumors. In this study, DNA and fowlpox virus recombinants expressing the E6F47R mutant of the HPV-16 E6 oncoprotein were generated, and their correct expression verified by RT-PCR, Western blotting and immunofluorescence. Immunization protocols were tested in a preventive or therapeutic pre-clinical mouse model of HPV-16 tumorigenicity using heterologous (DNA/FP) or homologous (DNA/DNA and FP/FP) prime/boost regimens. The immune responses and therapeutic efficacy were evaluated by ELISA, ELISPOT assays, and challenge with TC-1* cells. In the preventive protocol, while an anti-E6-specific humoral response was just detectable, a specific CD8(+) cytotoxic T-cell response was elicited in immunized mice. After the challenge, there was a delay in cancer appearance and a significant reduction of tumor volume in the two groups of E6-immunized mice, thus confirming the pivotal role of the CD8(+) T-cell response in the control of tumor growth in the absence of E6-specific antibodies. In the therapeutic protocol, in-vivo experiments resulted in a higher number of tumor-free mice after the homologous DNA/DNA or heterologous DNA/FP immunization. These data establish a preliminary indication for the prevention and treatment of HPV-related tumors by the use of DNA and avipox constructs as safe and effective immunogens following a prime/boost strategy. The combined use of recombinants expressing both E6 and E7 proteins might improve the antitumor efficacy, and should represent an important approach to

Poxvirus-based vaccine therapy for patients with advanced pancreatic cancer

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Seo Kang

2007-11-01

Full Text Available Abstract Purpose An open-label Phase 1 study of recombinant prime-boost poxviruses targeting CEA and MUC-1 in patients with advanced pancreatic cancer was conducted to determine safety, tolerability and obtain preliminary data on immune response and survival. Patients and methods Ten patients with advanced pancreatic cancer were treated on a Phase I clinical trial. The vaccination regimen consisted of vaccinia virus expressing tumor antigens carcinoembryonic antigen (CEA and mucin-1 (MUC-1 with three costimulatory molecules B7.1, ICAM-1 and LFA-3 (TRICOM (PANVAC-V and fowlpox virus expressing the same antigens and costimulatory molecules (PANVAC-F. Patients were primed with PANVAC-V followed by three booster vaccinations using PANVAC-F. Granulocyte-macrophage colony-stimulating factor (GM-CSF was used as a local adjuvant after each vaccination and for 3 consecutive days thereafter. Monthly booster vaccinations for up to 12 months were provided for patients without progressive disease. Peripheral blood was collected before, during and after vaccinations for immune analysis. Results The most common treatment-related adverse events were mild injection-site reactions. Antibody responses against vaccinia virus was observed in all 10 patients and antigen-specific T cell responses were observed in 5 out of 8 evaluable patients (62.5%. Median overall survival was 6.3 months and a significant increase in overall survival was noted in patients who generated anti CEA- and/or MUC-1-specific immune responses compared with those who did not (15.1 vs 3.9 months, respectively; P = .002. Conclusion Poxvirus vaccination is safe, well tolerated, and capable of generating antigen-specific immune responses in patients with advanced pancreatic cancer.

Principles for vaccine protection in chickens and domestic waterfowl against avian influenza: emphasis on Asian H5N1 high pathogenicity avian influenza.

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Swayne, David E

2006-10-01

The H5N1 highly pathogenic (HP) avian influenza (AI) epizootic began with reports of mortality from China in 1996 and, by June 2005, caused outbreaks of disease in nine additional Asian countries, affecting or resulting in culling of over 200 million birds. Vaccines can be used in programs to prevent, manage, or eradicate AI. However, vaccines should only be used as part of a comprehensive control strategy that also includes biosecurity, quarantine, surveillance and diagnostics, education, and elimination of infected poultry. Potent AI vaccines, when properly used, can prevent disease and death, increase resistance to infection, reduce field virus replication and shedding, and reduce virus transmission, but do not provide "sterilizing immunity" in the field; i.e., vaccination does not completely prevent AI virus replication. Inactivated AI vaccines and a recombinant fowlpox-H5-AI vaccine are licensed and used in various countries. Vaccines have been shown to protect chickens, geese, and ducks from H5 HPAI. The inactivated vaccines prevented disease and mortality in chickens and geese, and reduced the ability of the field virus to replicate in gastrointestinal and respiratory tracts. Although the Asian H5N1 HPAI virus did not cause disease or mortality in ducks, the use of inactivated vaccine did reduce field virus replication in the respiratory and intestinal tracts. The inactivated vaccine protected geese from morbidity and mortality, and reduced challenge virus replication. The recombinant fowlpox-H5-AI vaccine has provided similar protection, but the vaccine is used only in chickens and with the advantage of application at 1 day of age in the hatchery.

Reversion to virulence and efficacy of an attenuated canarypox vaccine in Hawai'i 'Amakihi (Hemignathus Virens)

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Atkinson, Carter T.; Wiegand, Kimberly C.; Triglia, Dennis; Jarvi, Susan I.

2012-01-01

Vaccines may be effective tools for protecting small populations of highly susceptible endangered, captive-reared, or translocated Hawaiian honeycreepers from introduced Avipoxvirus, but their efficacy has not been evaluated. An attenuated Canarypox vaccine that is genetically similar to one of two passerine Avipoxvirus isolates from Hawai‘i and distinct from Fowlpox was tested to evaluate whether Hawai‘i ‘Amakihi (Hemignathus virens) can be protected from wild isolates of Avipoxvirus from the Hawaiian Islands. Thirty-one (31) Hawai‘i ‘Amakihi were collected from high-elevation habitats on Mauna Kea Volcano, where pox transmission is rare, and randomly divided into two groups. One group was vaccinated with Poximune C®, whereas the other group received a sham vaccination with sterile water. Four of 15 (27%) vaccinated birds developed life-threatening disseminated lesions or lesions of unusually long duration, whereas one bird never developed a vaccine-associated lesion or “take.” After vaccine lesions healed, vaccinated birds were randomly divided into three groups of five and challenged with either a wild isolate of Fowlpox (FP) from Hawai‘i, a Hawai‘i ‘Amakihi isolate of a Canarypox-like virus (PV1), or a Hawai‘i ‘Amakihi isolate of a related, but distinct, passerine Avipoxvirus (PV2). Similarly, three random groups of five unvaccinated ‘Amakihi were challenged with the same virus isolates. Vaccinated and unvaccinated ‘Amakihi challenged with FP had transient infections with no clinical signs of infection. Mortality in vaccinated ‘Amakihi challenged with PV1 and PV2 ranged from 0% (0/5) for PV1 to 60% (3/5) for PV2. Mortality in unvaccinated ‘Amakihi ranged from 40% (2/5) for PV1 to 100% (5/5) for PV2. Although the vaccine provided some protection against PV1, both potential for vaccine reversion and low efficacy against PV2 preclude its use in captive or wild honeycreepers.

Sequential priming with simian immunodeficiency virus (SIV) DNA vaccines, with or without encoded cytokines, and a replicating adenovirus-SIV recombinant followed by protein boosting does not control a pathogenic SIVmac251 mucosal challenge.

Science.gov (United States)

Demberg, Thorsten; Boyer, Jean D; Malkevich, Nina; Patterson, L Jean; Venzon, David; Summers, Ebonita L; Kalisz, Irene; Kalyanaraman, V S; Lee, Eun Mi; Weiner, David B; Robert-Guroff, Marjorie

2008-11-01

Previously, combination DNA/nonreplicating adenovirus (Ad)- or poxvirus-vectored vaccines have strongly protected against SHIV(89.6P), DNAs expressing cytokines have modulated immunity elicited by DNA vaccines, and replication-competent Ad-recombinant priming and protein boosting has strongly protected against simian immunodeficiency virus (SIV) challenge. Here we evaluated a vaccine strategy composed of these promising components. Seven rhesus macaques per group were primed twice with multigenic SIV plasmid DNA with or without interleukin-12 (IL-12) DNA or IL-15 DNA. After a multigenic replicating Ad-SIV immunization, all groups received two booster immunizations with SIV gp140 and SIV Nef protein. Four control macaques received control DNA plasmids, empty Ad vector, and adjuvant. All vaccine components were immunogenic, but the cytokine DNAs had little effect. Macaques that received IL-15-DNA exhibited higher peak anti-Nef titers, a more rapid anti-Nef anamnestic response postchallenge, and expanded CD8(CM) T cells 2 weeks postchallenge compared to the DNA-only group. Other immune responses were indistinguishable between groups. Overall, no protection against intrarectal challenge with SIV(mac251) was observed, although immunized non-Mamu-A*01 macaques as a group exhibited a statistically significant 1-log decline in acute viremia compared to non-Mamu-A*01 controls. Possible factors contributing to the poor outcome include administration of cytokine DNAs to sites different from the Ad recombinants (intramuscular and intratracheal, respectively), too few DNA priming immunizations, a suboptimal DNA delivery method, failure to ensure delivery of SIV and cytokine plasmids to the same cell, and instability and short half-life of the IL-15 component. Future experiments should address these issues to determine if this combination approach is able to control a virulent SIV challenge.

Increased cellular immune responses and CD4+ T-cell proliferation correlate with reduced plasma viral load in SIV challenged recombinant simian varicella virus - simian immunodeficiency virus (rSVV-SIV vaccinated rhesus macaques

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Pahar Bapi

2012-08-01

Full Text Available Abstract Background An effective AIDS vaccine remains one of the highest priorities in HIV-research. Our recent study showed that vaccination of rhesus macaques with recombinant simian varicella virus (rSVV vector – simian immunodeficiency virus (SIV envelope and gag genes, induced neutralizing antibodies and cellular immune responses to SIV and also significantly reduced plasma viral loads following intravenous pathogenic challenge with SIVMAC251/CX1. Findings The purpose of this study was to define cellular immunological correlates of protection in rSVV-SIV vaccinated and SIV challenged animals. Immunofluorescent staining and multifunctional assessment of SIV-specific T-cell responses were evaluated in both Experimental and Control vaccinated animal groups. Significant increases in the proliferating CD4+ T-cell population and polyfunctional T-cell responses were observed in all Experimental-vaccinated animals compared with the Control-vaccinated animals. Conclusions Increased CD4+ T-cell proliferation was significantly and inversely correlated with plasma viral load. Increased SIV-specific polyfunctional cytokine responses and increased proliferation of CD4+ T-cell may be crucial to control plasma viral loads in vaccinated and SIVMAC251/CX1 challenged macaques.

Fragmentation of SIV-gag vaccine induces broader T cell responses.

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Adel Benlahrech

Full Text Available High mutation rates of human immunodeficiency virus (HIV allows escape from T cell recognition preventing development of effective T cell vaccines. Vaccines that induce diverse T cell immune responses would help overcome this problem. Using SIV gag as a model vaccine, we investigated two approaches to increase the breadth of the CD8 T cell response. Namely, fusion of vaccine genes to ubiquitin to target the proteasome and increase levels of MHC class I peptide complexes and gene fragmentation to overcome competition between epitopes for presentation and recognition.three vaccines were compared: full-length unmodified SIV-mac239 gag, full-length gag fused at the N-terminus to ubiquitin and 7 gag fragments of equal size spanning the whole of gag with ubiquitin-fused to the N-terminus of each fragment. Genes were cloned into a replication defective adenovirus vector and immunogenicity assessed in an in vitro human priming system. The breadth of the CD8 T cell response, defined by the number of distinct epitopes, was assessed by IFN-γ-ELISPOT and memory phenotype and cytokine production evaluated by flow cytometry. We observed an increase of two- to six-fold in the number of epitopes recognised in the ubiquitin-fused fragments compared to the ubiquitin-fused full-length gag. In contrast, although proteasomal targeting was achieved, there was a marked reduction in the number of epitopes recognised in the ubiquitin-fused full-length gag compared to the full-length unmodified gene, but there were no differences in the number of epitope responses induced by non-ubiquitinated full-length gag and the ubiquitin-fused mini genes. Fragmentation and ubiquitination did not affect T cell memory differentiation and polyfunctionality, though most responses were directed against the Ad5 vector.Fragmentation but not fusion with ubiquitin increases the breadth of the CD8 T vaccine response against SIV-mac239 gag. Thus gene fragmentation of HIV vaccines may maximise

Immunogenicity of seven new recombinant yellow fever viruses 17D expressing fragments of SIVmac239 Gag, Nef, and Vif in Indian rhesus macaques.

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Mauricio A Martins

Full Text Available An effective vaccine remains the best solution to stop the spread of human immunodeficiency virus (HIV. Cellular immune responses have been repeatedly associated with control of viral replication and thus may be an important element of the immune response that must be evoked by an efficacious vaccine. Recombinant viral vectors can induce potent T-cell responses. Although several viral vectors have been developed to deliver HIV genes, only a few have been advanced for clinical trials. The live-attenuated yellow fever vaccine virus 17D (YF17D has many properties that make it an attractive vector for AIDS vaccine regimens. YF17D is well tolerated in humans and vaccination induces robust T-cell responses that persist for years. Additionally, methods to manipulate the YF17D genome have been established, enabling the generation of recombinant (rYF17D vectors carrying genes from unrelated pathogens. Here, we report the generation of seven new rYF17D viruses expressing fragments of simian immunodeficiency virus (SIVmac239 Gag, Nef, and Vif. Studies in Indian rhesus macaques demonstrated that these live-attenuated vectors replicated in vivo, but only elicited low levels of SIV-specific cellular responses. Boosting with recombinant Adenovirus type-5 (rAd5 vectors resulted in robust expansion of SIV-specific CD8(+ T-cell responses, particularly those targeting Vif. Priming with rYF17D also increased the frequency of CD4(+ cellular responses in rYF17D/rAd5-immunized macaques compared to animals that received rAd5 only. The effect of the rYF17D prime on the breadth of SIV-specific T-cell responses was limited and we also found evidence that some rYF17D vectors were more effective than others at priming SIV-specific T-cell responses. Together, our data suggest that YF17D - a clinically relevant vaccine vector - can be used to prime AIDS virus-specific T-cell responses in heterologous prime boost regimens. However, it will be important to optimize rYF17D-based

Characterization and efficacy determination of commercially available Central American H5N2 avian influenza vaccines for poultry.

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Eggert, Dawn; Thomas, Colleen; Spackman, Erica; Pritchard, Nikki; Rojo, Francisco; Bublot, Michel; Swayne, David E

2010-06-23

A poultry vaccination program was implemented in Central America beginning in January 1995 to control both H5N2 low (LPAI) and high pathogenicity avian influenza. This study was conducted to identify seed strain composition and the efficacy of 10 commercially available H5 vaccines against challenge with H5N2 LPAI viruses isolated from Latin America in 2003. The original 1994 vaccine seed virus in commercial inactivated vaccines did not significantly reduce challenge virus shed titers. However, two seed strains of inactivated vaccines, genetically more closely related to the challenge virus, did significantly reduce titers of challenge virus shed from respiratory tract. In addition, a live recombinant fowlpox virus vaccine containing a more distantly related Eurasian lineage H5 gene insert significantly reduced respiratory shedding as compared to sham vaccinates. These results demonstrate the feasibility of identifying vaccine seed strains in commercial finished products for regulatory verification and the need for periodic challenge testing against current field strains in order to select efficacious vaccine seed strains. (c) 2010 Elsevier Ltd. All rights reserved.

Fowlpoxvirus recombinants coding for the CIITA gene increase the expression of endogenous MHC-II and Fowlpox Gag/Pro and Env SIV transgenes.

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Bissa, Massimiliano; Forlani, Greta; Zanotto, Carlo; Tosi, Giovanna; De Giuli Morghen, Carlo; Accolla, Roberto S; Radaelli, Antonia

2018-01-01

A complete eradication of an HIV infection has never been achieved by vaccination and the search for new immunogens that can induce long-lasting protective responses is ongoing. Avipoxvirus recombinants are host-restricted for replication to avian species and they do not have the undesired side effects induced by vaccinia recombinants. In particular, Fowlpox (FP) recombinants can express transgenes over long periods and can induce protective immunity in mammals, mainly due to CD4-dependent CD8+ T cells. In this context, the class II transactivator (CIITA) has a pivotal role in triggering the adaptive immune response through induction of the expression of class-II major histocompatibility complex molecule (MHC-II), that can present antigens to CD4+ T helper cells. Here, we report on construction of novel FPgp and FPenv recombinants that express the highly immunogenic SIV Gag-pro and Env structural antigens. Several FP-based recombinants, with single or dual genes, were also developed that express CIITA, driven from H6 or SP promoters. These recombinants were used to infect CEF and Vero cells in vitro and determine transgene expression, which was evaluated by real-time PCR and Western blotting. Subcellular localisation of the different proteins was evaluated by confocal microscopy, whereas HLA-DR or MHC-II expression was measured by flow cytometry. Fowlpox recombinants were also used to infect syngeneic T/SA tumour cells, then injected into Balb/c mice to elicit MHC-II immune response and define the presentation of the SIV transgene products in the presence or absence of FPCIITA. Antibodies to Env were measured by ELISA. Our data show that the H6 promoter was more efficient than SP to drive CIITA expression and that CIITA can enhance the levels of the gag/pro and env gene products only when infection is performed by FP single recombinants. Also, CIITA expression is higher when carried by FP single recombinants than when combined with FPgp or FPenv constructs and can

Avipoxviruses: infection biology and their use as vaccine vectors.

Science.gov (United States)

Weli, Simon C; Tryland, Morten

2011-02-03

Avipoxviruses (APVs) belong to the Chordopoxvirinae subfamily of the Poxviridae family. APVs are distributed worldwide and cause disease in domestic, pet and wild birds of many species. APVs are transmitted by aerosols and biting insects, particularly mosquitoes and arthropods and are usually named after the bird species from which they were originally isolated. The virus species Fowlpox virus (FWPV) causes disease in poultry and associated mortality is usually low, but in flocks under stress (other diseases, high production) mortality can reach up to 50%. APVs are also major players in viral vaccine vector development for diseases in human and veterinary medicine. Abortive infection in mammalian cells (no production of progeny viruses) and their ability to accommodate multiple gene inserts are some of the characteristics that make APVs promising vaccine vectors. Although abortive infection in mammalian cells conceivably represents a major vaccine bio-safety advantage, molecular mechanisms restricting APVs to certain hosts are not yet fully understood. This review summarizes the current knowledge relating to APVs, including classification, morphogenesis, host-virus interactions, diagnostics and disease, and also highlights the use of APVs as recombinant vaccine vectors.

Avipoxviruses: infection biology and their use as vaccine vectors

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Tryland Morten

2011-02-01

Full Text Available Abstract Avipoxviruses (APVs belong to the Chordopoxvirinae subfamily of the Poxviridae family. APVs are distributed worldwide and cause disease in domestic, pet and wild birds of many species. APVs are transmitted by aerosols and biting insects, particularly mosquitoes and arthropods and are usually named after the bird species from which they were originally isolated. The virus species Fowlpox virus (FWPV causes disease in poultry and associated mortality is usually low, but in flocks under stress (other diseases, high production mortality can reach up to 50%. APVs are also major players in viral vaccine vector development for diseases in human and veterinary medicine. Abortive infection in mammalian cells (no production of progeny viruses and their ability to accommodate multiple gene inserts are some of the characteristics that make APVs promising vaccine vectors. Although abortive infection in mammalian cells conceivably represents a major vaccine bio-safety advantage, molecular mechanisms restricting APVs to certain hosts are not yet fully understood. This review summarizes the current knowledge relating to APVs, including classification, morphogenesis, host-virus interactions, diagnostics and disease, and also highlights the use of APVs as recombinant vaccine vectors.

Combination of targeting gene-viro therapy with recombinant Fowl-pox viruses with HN and VP3 genes on mouse osteosarcoma.

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Zhang, Z-Y; Wang, L-Q; Fu, C-F; Li, X; Cui, Z-L; Zhang, J-Y; Xue, S-H; Sun, N; Xu, F

2013-03-01

Osteosarcoma is an aggressive cancerous neoplasm arising from primitive transformed cells of mesenchymal origin that exhibit osteoblastic differentiation and produce malignant osteoid. With the rapid development of tumor molecular biology, gene and viral therapy, a highly promising strategy for the treatment, has shown some therapeutic effects. To study the strategy of cooperative cancer gene therapy, previously, we explored the antitumor effects of recombinant Fowl-pox viruses (FPVs) with both HN (hemagglutinin-neuramidinase) and VP3 genes on mouse osteosarcoma. We constructed vFV-HN, vFV-VP3 and vFV-HN-VP3 inserting CAV VP3 gene, NDV HN gene into fowlpox virus. S180 osteosarcoma were transfected with Recombinant Fowl-pox viruses (FPVs). These cell lines stably expressing tagged proteins were selected by culturing in medium containing puromycin (2 µg/ml) and confirmed by immunoblotting and immunostaining. S180 osteosarcoma model with BALB/c mice and nude mice were established and the vFPV viruses as control, vFV-HN, vFV-VP3, vFV-HN-VP3 were injected into the tumor directly. The rate of tumor growth, tumor suppression and the sialic acid levels in serum were examined and the tumor tissues were analyzed by the method of immunohistochemistry. Flow cytometric analysis was performed using a FACSCalibur flow cytometer. A total of 100,000 events were analyzed for each sample and the experiment was repeated at least twice. Our data indicated that vFV-HN, vFV-VP3 and vFV-HN-VP3 all had growth inhibition effects, the inhibition rate of vFV-HN-VP3 group was 51.7%, which was higher than that of vFV-HN, vFV-VP3 group and control group (p genes into mouse osteosarcoma cancer cells can cause cell a specificity anti-tumor immune activity, suppress tumor growth, and increase the survival rate of the tumor within host.

Functional simian immunodeficiency virus Gag-specific CD8+ intraepithelial lymphocytes in the mucosae of SIVmac251- or simian-human immunodeficiency virus KU2-infected macaques

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Stevceva, Liljana; Moniuszko, Marcin; Alvarez, Xavier; Lackner, Andrew A.; Franchini, Genoveffa

2004-01-01

The vaginal and rectal mucosae are the first line of cellular immune defense to sexually transmitted human immunodeficiency virus type 1 (HIV-1) entry. Thus, intraepithelial lymphocytes (IELs) may be important in the immune response to HIV infection. Here we investigated whether functional IELs in mucosal compartments could be visualized by direct staining with a tetrameric complex specific for the simian immunodeficiency virus (SIV) immunodominant Gag epitope in either separated IEL cells or tissues of macaques infected with SIVmac251. Of the 15 Mamu-A*01-positive macaques studied here, eight were chronically infected with either SIVmac251 or simian-human immunodeficiency virus (SHIV) KU2 and the remaining seven were exposed mucosally to SIVmac251 and sacrificed within 48 h to assess the local immune response. Gag-specific CD8+ T-cells were found in separated IELs from the rectum, colon, jejunum, and vagina of most infected animals. Direct staining of tetramers also revealed their presence in intact tissue. These Gag-specific IELs expressed the activation marker CD69 and produced IFN-γ, suggesting an active immune response in this locale

Differences in time of virus appearance in the blood and virus-specific immune responses in intravenous and intrarectal primary SIVmac251 infection of rhesus macaques; a pilot study

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Washington Parks Robyn

2001-07-01

Full Text Available Abstract Background HIV-I can be transmitted by intravenous inoculation of contaminated blood or blood product or sexually through mucosal surfaces. Here we performed a pilot study in the SIVmac251 macaque model to address whether the route of viral entry influences the kinetics of the appearance and the size of virus-specific immune in different tissue compartments. Methods For this purpose, of 2 genetically defined Mamu-A*01-positive macaques, 1 was exposed intravenously and the other intrarectally to the same SIVmac251 viral stock and virus-specific CD8+ T-cells were measured within the first 12 days of infection in the blood and at day 12 in several tissues following euthanasia. Results Virus-specific CD8+ T-cell responses to Gag, Env, and particularly Tat appeared earlier in the blood of the animal exposed by the mucosal route than in the animal exposed intravenously. The magnitude of these virus-specific responses was consistently higher in the systemic tissues and GALT of the macaque exposed by the intravenous route, suggesting a higher viral burden in the tissues as reflected by the faster appearance of virus in plasma. Differences in the ability of the virus-specific CD8+ T-cells to respond in vitro to specific peptide stimulation were also observed and the greatest proliferative ability was found in the GALT of the animal infected by the intrarectal route. Conclusions These data may suggest that the natural mucosal barrier may delay viral spreading. The consequences of this observation, if confirmed in studies with a larger number of animals, may have implications in vaccine development.

A national multicenter phase 2 study of prostate-specific antigen (PSA) pox virus vaccine with sequential androgen ablation therapy in patients with PSA progression: ECOG 9802.

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DiPaola, Robert S; Chen, Yu-Hui; Bubley, Glenn J; Stein, Mark N; Hahn, Noah M; Carducci, Michael A; Lattime, Edmund C; Gulley, James L; Arlen, Philip M; Butterfield, Lisa H; Wilding, George

2015-09-01

E9802 was a phase 2 multi-institution study conducted to evaluate the safety and effectiveness of vaccinia and fowlpox prostate-specific antigen (PSA) vaccine (step 1) followed by combination with androgen ablation therapy (step 2) in patients with PSA progression without visible metastasis. To test the hypothesis that vaccine therapy in this early disease setting will be safe and have a biochemical effect that would support future studies of immunotherapy in patients with minimal disease burden. Patients who had PSA progression following local therapy were treated with PROSTVAC-V (vaccinia)/TRICOM on cycle 1 followed by PROSTVAC-F (fowlpox)/TRICOM for subsequent cycles in combination with granulocyte-macrophage colony-stimulating factor (step 1). Androgen ablation was added on progression (step 2). Step 1 primary end points included progression at 6 mo and characterization of change in PSA velocity pretreatment to post-treatment. Step 2 end points included PSA response with combined vaccine and androgen ablation. In step 1, 25 of 40 eligible patients (63%) were progression free at 6 mo after registration (90% confidence interval [CI], 48-75). The median pretreatment PSA velocity was 0.13 log(PSA)/mo, in contrast to median postregistration velocity of 0.09 log(PSA)/mo (p=0.02), which is an increase in median PSA doubling time from 5.3 mo to 7.7 mo. No grade ≥4 treatment-related toxicity was observed. In the 27 patients eligible and treated for step 2, 20 patients achieved a complete response (CR) at 7 mo (CR rate: 74%; 90% CI, 57-87). Although supportive of larger studies in the cooperative group setting, this study is limited by the small number of patients and the absence of a control group as in a phase 3 study. A viral PSA vaccine can be administered safely in the multi-institutional cooperative group setting to patients with minimal disease volume alone and combined with androgen ablation, supporting the feasibility of future phase 3 studies in this

Role of complement and antibodies in controlling infection with pathogenic simian immunodeficiency virus (SIV in macaques vaccinated with replication-deficient viral vectors

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Strasak Alexander

2009-06-01

Full Text Available Abstract Background We investigated the interplay between complement and antibodies upon priming with single-cycle replicating viral vectors (SCIV encoding SIV antigens combined with Adeno5-SIV or SCIV pseudotyped with murine leukemia virus envelope boosting strategies. The vaccine was applied via spray-immunization to the tonsils of rhesus macaques and compared with systemic regimens. Results Independent of the application regimen or route, viral loads were significantly reduced after challenge with SIVmac239 (p Conclusion The heterologous prime-boost strategy with replication-deficient viral vectors administered exclusively via the tonsils did not induce any neutralizing antibodies before challenge. However, after challenge, comparable SIV-specific humoral immune responses were observed in all vaccinated animals. Immunization with single cycle immunodeficiency viruses mounts humoral immune responses comparable to live-attenuated immunodeficiency virus vaccines.

Low dose rectal inoculation of rhesus macaques by SIV smE660 or SIVmac251 recapitulates

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Hraber, Peter [Los Alamos National Laboratory; Giorgi, Elena E [Los Alamos National Laboratory; Keele, Brandon [UNIV OF ALABAMA; Li, Hui [UNIV OF ALABAMA; Learn, Gerald [UNIV OF ALABAMA

2008-01-01

We recently developed a novel strategy to identify transmitted HIV-1 genomes in acutely infected humans using single-genome amplification and a model of random virus evolution. Here, we used this approach to determine the molecular features of simian immunodeficiency virus (SIV) transmission in 18 experimentally infected Indian rhesus macaques. Animals were inoculated intrarectally (i.r.) or intravenously (i.v.) with stocks of SIVmac251 or SIVsmE660 that exhibited sequence diversity typical of early-chronic HIV-1 infection. 987 full-length SIV env sequences (median of 48 per animal) were determined from plasma virion RNA 1--5 wk after infection. i.r. inoculation was followed by productive infection by one or a few viruses (median 1; range 1--5) that diversified randomly with near starlike phylogeny and a Poisson distribution of mutations. Consensus viral sequences from ramp-up and peak viremia were identical to viruses found in the inocula or differed from them by only one or a few nucleotides, providing direct evidence that early plasma viral sequences coalesce to transmitted/founder viruses. i.v. infection was >2,000-fold more efficient than i.r. infection, and viruses transmitted by either route represented the full genetic spectra of the inocula. These findings identify key similarities in mucosal transmission and early diversification between SIV and HIV-1, and thus validate the SIV-macaque mucosal infection model for HIV-1 vaccine and microbicide research.

Modification of a loop sequence between α-helices 6 and 7 of virus capsid (CA protein in a human immunodeficiency virus type 1 (HIV-1 derivative that has simian immunodeficiency virus (SIVmac239 vif and CA α-helices 4 and 5 loop improves replication in cynomolgus monkey cells

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Adachi Akio

2009-08-01

Full Text Available Abstract Background Human immunodeficiency virus type 1 (HIV-1 productively infects only humans and chimpanzees but not cynomolgus or rhesus monkeys while simian immunodeficiency virus isolated from macaque (SIVmac readily establishes infection in those monkeys. Several HIV-1 and SIVmac chimeric viruses have been constructed in order to develop an animal model for HIV-1 infection. Construction of an HIV-1 derivative which contains sequences of a SIVmac239 loop between α-helices 4 and 5 (L4/5 of capsid protein (CA and the entire SIVmac239 vif gene was previously reported. Although this chimeric virus could grow in cynomolgus monkey cells, it did so much more slowly than did SIVmac. It was also reported that intrinsic TRIM5α restricts the post-entry step of HIV-1 replication in rhesus and cynomolgus monkey cells, and we previously demonstrated that a single amino acid in a loop between α-helices 6 and 7 (L6/7 of HIV type 2 (HIV-2 CA determines the susceptibility of HIV-2 to cynomolgus monkey TRIM5α. Results In the study presented here, we replaced L6/7 of HIV-1 CA in addition to L4/5 and vif with the corresponding segments of SIVmac. The resultant HIV-1 derivatives showed enhanced replication capability in established T cell lines as well as in CD8+ cell-depleted primary peripheral blood mononuclear cells from cynomolgus monkey. Compared with the wild type HIV-1 particles, the viral particles produced from a chimeric HIV-1 genome with those two SIVmac loops were less able to saturate the intrinsic restriction in rhesus monkey cells. Conclusion We have succeeded in making the replication of simian-tropic HIV-1 in cynomolgus monkey cells more efficient by introducing into HIV-1 the L6/7 CA loop from SIVmac. It would be of interest to determine whether HIV-1 derivatives with SIVmac CA L4/5 and L6/7 can establish infection of cynomolgus monkeys in vivo.

Outbreaks of Pox Disease Due to Canarypox-Like and Fowlpox-Like Viruses in Large-Scale Houbara Bustard Captive-Breeding Programmes, in Morocco and the United Arab Emirates.

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Le Loc'h, G; Paul, M C; Camus-Bouclainville, C; Bertagnoli, S

2016-12-01

Infectious diseases can be serious threats for the success of reinforcement programmes of endangered species. Houbara Bustard species (Chlamydotis undulata and Chlamydotis macqueenii), whose populations declined in the last decades, have been captive-bred for conservation purposes for more than 15 years in North Africa and the Middle East. Field observations show that pox disease, caused by avipoxviruses (APV), regularly emerges in conservation projects of Houbara Bustard, despite a very strict implementation of both vaccination and biosecurity. Data collected from captive flocks of Houbara Bustard in Morocco from 2006 through 2013 and in the United Arab Emirates from 2011 through 2013 were analysed, and molecular investigations were carried out to define the virus strains involved. Pox cases (n = 2311) were observed during more than half of the year (88% of the months in Morocco, 54% in the United Arab Emirates). Monthly morbidity rates showed strong variations across the time periods considered, species and study sites: Four outbreaks were described during the study period on both sites. Molecular typing revealed that infections were mostly due to canarypox-like viruses in Morocco while fowlpox-like viruses were predominant in the United Arab Emirates. This study highlights that APV remain a major threat to consider in bird conservation initiatives. © 2015 Blackwell Verlag GmbH.

Diverse uses of feathers with emphasis on diagnosis of avian viral infections and vaccine virus monitoring

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I Davidson

2009-09-01

Full Text Available The large amounts of feathers produced by the poultry industry, that is considered as a waste was explored for possible uses in various industries, such as meals for animals, biofuels, biodegradable plastic materials, combating water pollution and more. That review mentions these uses, but concentrate on the utilization of feathers for the diagnosis of viral infections and for monitoring vaccine viruses in chickens after vaccination. The viral diseases in which diagnosis using nucleic acids extracted from the feather shafts was described are, Marek's disease virus, circoviruses, chicken anemia virus, fowlpox virus, avian retroviruses, avian influenza virus and infectious laryngotracheitis virus. In two cases, of Marek's disease virus and of infectious laryngotracheitis virus, the differentiation of vaccine and wild-type viruses from feather shafts was made possible, thus allowing for monitoring the vaccination efficacy. The present review demonstrates also the stability of DNA viruses in feather shafts, and the possible evaluation of environmental dissemination of pathogens. When viruses are transmitted vertically, like in the cases of the retrovirus REV, a teratogenic effect on the development of feathers of the day-old newly hatched chick might occur in the case of avian influenza and the chicken anemia virus, which might indicate on a viral infection.

Suppressing active replication of a live attenuated simian immunodeficiency virus vaccine does not abrogate protection from challenge

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Gabriel, Benjamin; Fiebig, Uwe; Hohn, Oliver [Robert Koch-Institut, Berlin (Germany); Plesker, Roland; Coulibaly, Cheick; Cichutek, Klaus; Mühlebach, Michael D. [Paul-Ehrlich-Institut, Langen (Germany); Bannert, Norbert; Kurth, Reinhard [Robert Koch-Institut, Berlin (Germany); Norley, Stephen, E-mail: NorleyS@rki.de [Robert Koch-Institut, Berlin (Germany)

2016-02-15

Although safety concerns preclude the use of live attenuated HIV vaccines in humans, they provide a useful system for identifying the elusive correlates of protective immunity in the SIV/macaque animal model. However, a number of pieces of evidence suggest that protection may result from prior occupancy of susceptible target cells by the vaccine virus rather than the immune response. To address this, we developed a Nef-deletion variant of an RT-SHIV whose active replication could be shut off by treatment with RT-inhibitors. Groups of macaques were inoculated with the ∆Nef-RT-SHIV and immune responses allowed to develop before antiretroviral treatment and subsequent challenge with wild-type SIVmac239. Vaccinated animals either resisted infection fully or significantly controlled the subsequent viremia. However, there was no difference between animals undergoing replication of the vaccine virus and those without. This strongly suggests that competition for available target cells does not play a role in protection. - Highlights: • A Nef-deleted RT-SHIV was used as a live attenuated vaccine in macaques. • Vaccine virus replication was shut down to investigate its role in protection. • Ongoing vaccine virus replication did not appear to be necessary for protection. • An analysis of T- and B-cell responses failed to identify a correlate of protection.

Suppressing active replication of a live attenuated simian immunodeficiency virus vaccine does not abrogate protection from challenge

International Nuclear Information System (INIS)

Gabriel, Benjamin; Fiebig, Uwe; Hohn, Oliver; Plesker, Roland; Coulibaly, Cheick; Cichutek, Klaus; Mühlebach, Michael D.; Bannert, Norbert; Kurth, Reinhard; Norley, Stephen

2016-01-01

Although safety concerns preclude the use of live attenuated HIV vaccines in humans, they provide a useful system for identifying the elusive correlates of protective immunity in the SIV/macaque animal model. However, a number of pieces of evidence suggest that protection may result from prior occupancy of susceptible target cells by the vaccine virus rather than the immune response. To address this, we developed a Nef-deletion variant of an RT-SHIV whose active replication could be shut off by treatment with RT-inhibitors. Groups of macaques were inoculated with the ∆Nef-RT-SHIV and immune responses allowed to develop before antiretroviral treatment and subsequent challenge with wild-type SIVmac239. Vaccinated animals either resisted infection fully or significantly controlled the subsequent viremia. However, there was no difference between animals undergoing replication of the vaccine virus and those without. This strongly suggests that competition for available target cells does not play a role in protection. - Highlights: • A Nef-deleted RT-SHIV was used as a live attenuated vaccine in macaques. • Vaccine virus replication was shut down to investigate its role in protection. • Ongoing vaccine virus replication did not appear to be necessary for protection. • An analysis of T- and B-cell responses failed to identify a correlate of protection.

Vaccination of carp against SVCV with an oral DNA vaccine or an insect cells-based subunit vaccine.

Science.gov (United States)

Embregts, C W E; Rigaudeau, D; Tacchi, L; Pijlman, G P; Kampers, L; Veselý, T; Pokorová, D; Boudinot, P; Wiegertjes, G F; Forlenza, M

2018-03-19

We recently reported on a successful vaccine for carp against SVCV based on the intramuscular injection of a DNA plasmid encoding the SVCV glycoprotein (SVCV-G). This shows that the intramuscular (i.m.) route of vaccination is suitable to trigger protective responses against SVCV, and that the SVCV G-protein is a suitable vaccine antigen. Yet, despite the general success of DNA vaccines, especially against fish rhabdoviruses, their practical implementation still faces legislative as well as consumer's acceptance concerns. Furthermore, the i.m. route of plasmid administration is not easily combined with most of the current vaccination regimes largely based on intraperitoneal or immersion vaccination. For this reason, in the current study we evaluated possible alternatives to a DNA-based i.m. injectable vaccine using the SVCV-G protein as the vaccine antigen. To this end, we tested two parallel approaches: the first based on the optimization of an alginate encapsulation method for oral delivery of DNA and protein antigens; the second based on the baculovirus recombinant expression of transmembrane SVCV-G protein in insect cells, administered as whole-cell subunit vaccine through the oral and injection route. In addition, in the case of the oral DNA vaccine, we also investigated the potential benefits of the mucosal adjuvants Escherichia coli lymphotoxin subunit B (LTB). Despite the use of various vaccine types, doses, regimes, and administration routes, no protection was observed, contrary to the full protection obtained with our reference i.m. DNA vaccine. The limited protection observed under the various conditions used in this study, the nature of the host, of the pathogen, the type of vaccine and encapsulation method, will therefore be discussed in details to provide an outlook for future vaccination strategies against SVCV. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Adolescent Attitudes toward Influenza Vaccination and Vaccine Uptake in a School-Based Influenza Vaccination Intervention: A Mediation Analysis

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Painter, Julia E.; Sales, Jessica M.; Pazol, Karen; Wingood, Gina M.; Windle, Michael; Orenstein, Walter A.; DiClemente, Ralph J.

2011-01-01

Background: School-based vaccination programs may provide an effective strategy to immunize adolescents against influenza. This study examined whether adolescent attitudes toward influenza vaccination mediated the relationship between receipt of a school-based influenza vaccination intervention and vaccine uptake. Methods: Participants were…

Algae-based oral recombinant vaccines

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Specht, Elizabeth A.; Mayfield, Stephen P.

2014-01-01

Recombinant subunit vaccines are some of the safest and most effective vaccines available, but their high cost and the requirement of advanced medical infrastructure for administration make them impractical for many developing world diseases. Plant-based vaccines have shifted that paradigm by paving the way for recombinant vaccine production at agricultural scale using an edible host. However, enthusiasm for “molecular pharming” in food crops has waned in the last decade due to difficulty in developing transgenic crop plants and concerns of contaminating the food supply. Microalgae could be poised to become the next candidate in recombinant subunit vaccine production, as they present several advantages over terrestrial crop plant-based platforms including scalable and contained growth, rapid transformation, easily obtained stable cell lines, and consistent transgene expression levels. Algae have been shown to accumulate and properly fold several vaccine antigens, and efforts are underway to create recombinant algal fusion proteins that can enhance antigenicity for effective orally delivered vaccines. These approaches have the potential to revolutionize the way subunit vaccines are made and delivered – from costly parenteral administration of purified protein, to an inexpensive oral algae tablet with effective mucosal and systemic immune reactivity. PMID:24596570

Algae-based oral recombinant vaccines

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Elizabeth A Specht

2014-02-01

Full Text Available Recombinant subunit vaccines are some of the safest and most effective vaccines available, but their high cost and the requirement of advanced medical infrastructure for administration make them impractical for many developing world diseases. Plant-based vaccines have shifted that paradigm by paving the way for recombinant vaccine production at agricultural scale using an edible host. However, enthusiasm for molecular pharming in food crops has waned in the last decade due to difficulty in developing transgenic crop plants and concerns of contaminating the food supply. Microalgae are poised to become the next candidate in recombinant subunit vaccine production, and they present several advantages over terrestrial crop plant-based platforms including scalable and contained growth, rapid transformation, easily obtained stable cell lines, and consistent transgene expression levels. Algae have been shown to accumulate and properly fold several vaccine antigens, and efforts are underway to create recombinant algal fusion proteins that can enhance antigenicity for effective orally-delivered vaccines. These approaches have the potential to revolutionize the way subunit vaccines are made and delivered – from costly parenteral administration of purified protein, to an inexpensive oral algae tablet with effective mucosal and system immune reactivity.

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

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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.

Single-cycle immunodeficiency viruses provide strategies for uncoupling in vivo expression levels from viral replicative capacity and for mimicking live-attenuated SIV vaccines

International Nuclear Information System (INIS)

Kuate, Seraphin; Stahl-Hennig, Christiane; Haaft, Peter ten; Heeney, Jonathan; Ueberla, Klaus

2003-01-01

To reduce the risks associated with live-attenuated immunodeficiency virus vaccines, single-cycle immunodeficiency viruses (SCIVs) were developed by primer complementation and production of the vaccine in the absence of vif in a vif-independent cell line. After a single intravenous injection of SCIVs into rhesus monkeys, peak viral RNA levels of 10 3 to 10 4 copies/ml plasma were observed, indicating efficient expression of SCIV in the vaccinee. After booster immunizations with SCIVs, SIV-specific humoral and cellular immune responses were observed. Although the vaccine doses used in this pilot study could not protect vaccinees from subsequent intravenous challenge with pathogenic SIVmac239, our results demonstrate that the novel SCIV approach allows us to uncouple in vivo expression levels from the viral replicative capacity facilitating the analysis of the relationship between viral expression levels or viral genes and immune responses induced by SIV

Rational design of gene-based vaccines.

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Barouch, Dan H

2006-01-01

Vaccine development has traditionally been an empirical discipline. Classical vaccine strategies include the development of attenuated organisms, whole killed organisms, and protein subunits, followed by empirical optimization and iterative improvements. While these strategies have been remarkably successful for a wide variety of viruses and bacteria, these approaches have proven more limited for pathogens that require cellular immune responses for their control. In this review, current strategies to develop and optimize gene-based vaccines are described, with an emphasis on novel approaches to improve plasmid DNA vaccines and recombinant adenovirus vector-based vaccines. Copyright 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Cellular based cancer vaccines

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Hansen, M; Met, Ö; Svane, I M

2012-01-01

Cancer vaccines designed to re-calibrate the existing host-tumour interaction, tipping the balance from tumor acceptance towards tumor control holds huge potential to complement traditional cancer therapies. In general, limited success has been achieved with vaccines composed of tumor...... to transiently affect in vitro migration via autocrine receptor-mediated endocytosis of CCR7. In the current review, we discuss optimal design of DC maturation focused on pre-clinical as well as clinical results from standard and polarized dendritic cell based cancer vaccines....

Vaxjo: A Web-Based Vaccine Adjuvant Database and Its Application for Analysis of Vaccine Adjuvants and Their Uses in Vaccine Development

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Samantha Sayers

2012-01-01

Full Text Available Vaccine adjuvants are compounds that enhance host immune responses to co-administered antigens in vaccines. Vaxjo is a web-based central database and analysis system that curates, stores, and analyzes vaccine adjuvants and their usages in vaccine development. Basic information of a vaccine adjuvant stored in Vaxjo includes adjuvant name, components, structure, appearance, storage, preparation, function, safety, and vaccines that use this adjuvant. Reliable references are curated and cited. Bioinformatics scripts are developed and used to link vaccine adjuvants to different adjuvanted vaccines stored in the general VIOLIN vaccine database. Presently, 103 vaccine adjuvants have been curated in Vaxjo. Among these adjuvants, 98 have been used in 384 vaccines stored in VIOLIN against over 81 pathogens, cancers, or allergies. All these vaccine adjuvants are categorized and analyzed based on adjuvant types, pathogens used, and vaccine types. As a use case study of vaccine adjuvants in infectious disease vaccines, the adjuvants used in Brucella vaccines are specifically analyzed. A user-friendly web query and visualization interface is developed for interactive vaccine adjuvant search. To support data exchange, the information of vaccine adjuvants is stored in the Vaccine Ontology (VO in the Web Ontology Language (OWL format.

Vaxjo: a web-based vaccine adjuvant database and its application for analysis of vaccine adjuvants and their uses in vaccine development.

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Sayers, Samantha; Ulysse, Guerlain; Xiang, Zuoshuang; He, Yongqun

2012-01-01

Vaccine adjuvants are compounds that enhance host immune responses to co-administered antigens in vaccines. Vaxjo is a web-based central database and analysis system that curates, stores, and analyzes vaccine adjuvants and their usages in vaccine development. Basic information of a vaccine adjuvant stored in Vaxjo includes adjuvant name, components, structure, appearance, storage, preparation, function, safety, and vaccines that use this adjuvant. Reliable references are curated and cited. Bioinformatics scripts are developed and used to link vaccine adjuvants to different adjuvanted vaccines stored in the general VIOLIN vaccine database. Presently, 103 vaccine adjuvants have been curated in Vaxjo. Among these adjuvants, 98 have been used in 384 vaccines stored in VIOLIN against over 81 pathogens, cancers, or allergies. All these vaccine adjuvants are categorized and analyzed based on adjuvant types, pathogens used, and vaccine types. As a use case study of vaccine adjuvants in infectious disease vaccines, the adjuvants used in Brucella vaccines are specifically analyzed. A user-friendly web query and visualization interface is developed for interactive vaccine adjuvant search. To support data exchange, the information of vaccine adjuvants is stored in the Vaccine Ontology (VO) in the Web Ontology Language (OWL) format.

Development of an epitope-based HIV-1 vaccine strategy from HIV-1 lipopeptide to dendritic-based vaccines.

Science.gov (United States)

Surenaud, Mathieu; Lacabaratz, Christine; Zurawski, Gérard; Lévy, Yves; Lelièvre, Jean-Daniel

2017-10-01

Development of a safe, effective and globally affordable Human Immunodeficiency Virus strain 1 (HIV-1) vaccine offers the best hope for future control of the HIV-1 pandemic. However, with the exception of the recent RV144 trial, which elicited a modest level of protection against infection, no vaccine candidate has shown efficacy in preventing HIV-1 infection or in controlling virus replication in humans. There is also a great need for a successful immunotherapeutic vaccine since combination antiretroviral therapy (cART) does not eliminate the reservoir of HIV-infected cells. But to date, no vaccine candidate has proven to significantly alter the natural history of an individual with HIV-1 infection. Areas covered: For over 25 years, the ANRS (France Recherche Nord&Sud Sida-HIV hépatites) has been committed to an original program combining basic science and clinical research developing an epitope-based vaccine strategy to induce a multiepitopic cellular response against HIV-1. This review describes the evolution of concepts, based on strategies using HIV-1 lipopeptides towards the use of dendritic cell (DC) manipulation. Expert commentary: Understanding the crucial role of DCs in immune responses allowed moving from the non-specific administration of HIV-1 sequences with lipopeptides to DC-based vaccines. These DC-targeting strategies should improve HIV-1 vaccine efficacy.

Ontology-based Brucella vaccine literature indexing and systematic analysis of gene-vaccine association network

Science.gov (United States)

2011-01-01

Background Vaccine literature indexing is poorly performed in PubMed due to limited hierarchy of Medical Subject Headings (MeSH) annotation in the vaccine field. Vaccine Ontology (VO) is a community-based biomedical ontology that represents various vaccines and their relations. SciMiner is an in-house literature mining system that supports literature indexing and gene name tagging. We hypothesize that application of VO in SciMiner will aid vaccine literature indexing and mining of vaccine-gene interaction networks. As a test case, we have examined vaccines for Brucella, the causative agent of brucellosis in humans and animals. Results The VO-based SciMiner (VO-SciMiner) was developed to incorporate a total of 67 Brucella vaccine terms. A set of rules for term expansion of VO terms were learned from training data, consisting of 90 biomedical articles related to Brucella vaccine terms. VO-SciMiner demonstrated high recall (91%) and precision (99%) from testing a separate set of 100 manually selected biomedical articles. VO-SciMiner indexing exhibited superior performance in retrieving Brucella vaccine-related papers over that obtained with MeSH-based PubMed literature search. For example, a VO-SciMiner search of "live attenuated Brucella vaccine" returned 922 hits as of April 20, 2011, while a PubMed search of the same query resulted in only 74 hits. Using the abstracts of 14,947 Brucella-related papers, VO-SciMiner identified 140 Brucella genes associated with Brucella vaccines. These genes included known protective antigens, virulence factors, and genes closely related to Brucella vaccines. These VO-interacting Brucella genes were significantly over-represented in biological functional categories, including metabolite transport and metabolism, replication and repair, cell wall biogenesis, intracellular trafficking and secretion, posttranslational modification, and chaperones. Furthermore, a comprehensive interaction network of Brucella vaccines and genes were

Variability of bio-clinical parameters in Chinese-origin Rhesus macaques infected with simian immunodeficiency virus: a nonhuman primate AIDS model.

Directory of Open Access Journals (Sweden)

Song Chen

Full Text Available BACKGROUND: Although Chinese-origin Rhesus macaques (Ch RhMs infected with simian immunodeficiency virus (SIV have been used for many years to evaluate the efficacy of AIDS vaccines and therapeutics, the bio-clinical variability of such a nonhuman primate AIDS model was so far not established. METHODOLOGY/PRINCIPAL FINDINGS: By randomizing 150 (78 male and 72 female Ch RhMs with diverse MHC class I alleles into 3 groups (50 animals per group challenged with intrarectal (i.r. SIVmac239, intravenous (i.v. SIVmac239, or i.v. SIVmac251, we evaluated variability in bio-clinical endpoints for 118 weeks. All SIV-challenged Ch RhMs became seropositive for SIV during 1-2 weeks. Plasma viral load (VL peaked at weeks 1-2 and then declined to set-point levels as from week 5. The set-point VL was 30 fold higher in SIVmac239 (i.r. or i.v.-infected than in SIVmac251 (i.v.-infected animals. This difference in plasma VL increased overtime (>100 fold as from week 68. The rates of progression to AIDS or death were more rapid in SIVmac239 (i.r. or i.v.-infected than in SIVmac251 (i.v.-infected animals. No significant difference in bio-clinical endpoints was observed in animals challenged with i.r. or i.v. SIVmac239. The variability (standard deviation in peak/set-point VL was nearly one-half lower in animals infected with SIVmac239 (i.r. or i.v. than in those infected with SIVmac251 (i.v., allowing that the same treatment-related difference can be detected with one-half fewer animals using SIVmac239 than using SIVmac251. CONCLUSION/SIGNIFICANCE: These results provide solid estimates of variability in bio-clinical endpoints needed when designing studies using the Ch RhM SIV model and contribute to the improving quality and standardization of preclinical studies.

The European Regulatory Environment of RNA-Based Vaccines.

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Hinz, Thomas; Kallen, Kajo; Britten, Cedrik M; Flamion, Bruno; Granzer, Ulrich; Hoos, Axel; Huber, Christoph; Khleif, Samir; Kreiter, Sebastian; Rammensee, Hans-Georg; Sahin, Ugur; Singh-Jasuja, Harpreet; Türeci, Özlem; Kalinke, Ulrich

2017-01-01

A variety of different mRNA-based drugs are currently in development. This became possible, since major breakthroughs in RNA research during the last decades allowed impressive improvements of translation, stability and delivery of mRNA. This article focuses on antigen-encoding RNA-based vaccines that are either directed against tumors or pathogens. mRNA-encoded vaccines are developed both for preventive or therapeutic purposes. Most mRNA-based vaccines are directly administered to patients. Alternatively, primary autologous cells from cancer patients are modified ex vivo by the use of mRNA and then are adoptively transferred to patients. In the EU no regulatory guidelines presently exist that specifically address mRNA-based vaccines. The existing regulatory framework, however, clearly defines that mRNA-based vaccines in most cases have to be centrally approved. Interestingly, depending on whether RNA-based vaccines are directed against tumors or infectious disease, they are formally considered gene therapy products or not, respectively. Besides an overview on the current clinical use of mRNA vaccines in various therapeutic areas a detailed discussion of the current regulatory situation is provided and regulatory perspectives are discussed.

HIV vaccine research and discovery in the nonhuman primates model: a unified theory in acquisition prevention and control of SIV infection.

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Lynch, Rebecca M; Yamamoto, Takuya; McDermott, Adrian B

2013-07-01

Here we highlight the latest advances in HIV vaccine concepts that will expand our knowledge on how to elicit effective acquisition-prevention and/or control of simian immunodeficiency virus (SIV) replication in the nonhuman primate (NHP) model. In the context of the promising analyses from the RV144 Thai Trial and the effective control of SIV replication exerted by rhCMV-(SIV) elicited EM CD8 T cells, the HIV field has recently shifted toward vaccine concepts that combine protection from acquisition with effective control of SIV replication. Current studies in the NHP model have demonstrated the efficacy of HIV-neutralizing antibodies via passive transfer, the potential importance of the CD4 Tfh subset, the ability to effectively model the RV144 vaccine trial and the capacity of an Ad26 prime and modified vaccinia Ankara virus boost to elicit Env-specific antibody and cellular responses that both limit acquisition and control heterologous SIVmac251 challenge. The latest work in the NHP model suggests that the next generation HIV-1 vaccines should aim to provoke a comprehensive adaptive immune response for both prevention of SIV acquisition as well as control of replication in breakthrough infection.

Chikungunya Virus Vaccines: Viral Vector-Based Approaches.

Science.gov (United States)

Ramsauer, Katrin; Tangy, Frédéric

2016-12-15

In 2013, a major chikungunya virus (CHIKV) epidemic reached the Americas. In the past 2 years, >1.7 million people have been infected. In light of the current epidemic, with millions of people in North and South America at risk, efforts to rapidly develop effective vaccines have increased. Here, we focus on CHIKV vaccines that use viral-vector technologies. This group of vaccine candidates shares an ability to potently induce humoral and cellular immune responses by use of highly attenuated and safe vaccine backbones. So far, well-described vectors such as modified vaccinia virus Ankara, complex adenovirus, vesicular stomatitis virus, alphavirus-based chimeras, and measles vaccine Schwarz strain (MV/Schw) have been described as potential vaccines. We summarize here the recent data on these experimental vaccines, with a focus on the preclinical and clinical activities on the MV/Schw-based candidate, which is the first CHIKV-vectored vaccine that has completed a clinical trial. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

L1R, A27L, A33R and B5R vaccinia virus genes expressed by fowlpox recombinants as putative novel orthopoxvirus vaccines

OpenAIRE

Pacchioni, Sole Maria; Bissa, Massimiliano; Zanotto, Carlo; Morghen, Carlo De Giuli; Illiano, Elena; Radaelli, Antonia

2013-01-01

Background The traditional smallpox vaccine, administered by scarification, was discontinued in the general population from 1980, because of the absence of new smallpox cases. However, the development of an effective prophylactic vaccine against smallpox is still necessary, to protect from the threat of deliberate release of the variola virus for bioterrorism and from new zoonotic infections, and to improve the safety of the traditional vaccine. Preventive vaccination still remains the most e...

A potential disruptive technology in vaccine development: gene-based vaccines and their application to infectious diseases.

Science.gov (United States)

Kaslow, David C

2004-10-01

Vaccine development requires an amalgamation of disparate disciplines and has unique economic and regulatory drivers. Non-viral gene-based delivery systems, such as formulated plasmid DNA, are new and potentially disruptive technologies capable of providing 'cheaper, simpler, and more convenient-to-use' vaccines. Typically and somewhat ironically, disruptive technologies have poorer product performance, at least in the near-term, compared with the existing conventional technologies. Because successful product development requires that the product's performance must meet or exceed the efficacy threshold for a desired application, the appropriate selection of the initial product applications for a disruptive technology is critical for its successful evolution. In this regard, the near-term successes of gene-based vaccines will likely be for protection against bacterial toxins and acute viral and bacterial infections. Recent breakthroughs, however, herald increasing rather than languishing performance improvements in the efficacy of gene-based vaccines. Whether gene-based vaccines ultimately succeed in eliciting protective immunity in humans to persistent intracellular pathogens, such as HIV, malaria and tuberculosis, for which the conventional vaccine technologies have failed, remains to be determined. A success against any one of the persistent intracellular pathogens would be sufficient proof that gene-based vaccines represent a disruptive technology against which future vaccine technologies will be measured.

A population-based evaluation of a publicly funded, school-based HPV vaccine program in British Columbia, Canada: parental factors associated with HPV vaccine receipt.

Science.gov (United States)

Ogilvie, Gina; Anderson, Maureen; Marra, Fawziah; McNeil, Shelly; Pielak, Karen; Dawar, Meena; McIvor, Marilyn; Ehlen, Thomas; Dobson, Simon; Money, Deborah; Patrick, David M; Naus, Monika

2010-05-04

Information on factors that influence parental decisions for actual human papillomavirus (HPV) vaccine receipt in publicly funded, school-based HPV vaccine programs for girls is limited. We report on the level of uptake of the first dose of the HPV vaccine, and determine parental factors associated with receipt of the HPV vaccine, in a publicly funded school-based HPV vaccine program in British Columbia, Canada. All parents of girls enrolled in grade 6 during the academic year of September 2008-June 2009 in the province of British Columbia were eligible to participate. Eligible households identified through the provincial public health information system were randomly selected and those who consented completed a validated survey exploring factors associated with HPV vaccine uptake. Bivariate and multivariate analyses were conducted to calculate adjusted odds ratios to identify the factors that were associated with parents' decision to vaccinate their daughter(s) against HPV. 2,025 parents agreed to complete the survey, and 65.1% (95% confidence interval [CI] 63.1-67.1) of parents in the survey reported that their daughters received the first dose of the HPV vaccine. In the same school-based vaccine program, 88.4% (95% CI 87.1-89.7) consented to the hepatitis B vaccine, and 86.5% (95% CI 85.1-87.9) consented to the meningococcal C vaccine. The main reasons for having a daughter receive the HPV vaccine were the effectiveness of the vaccine (47.9%), advice from a physician (8.7%), and concerns about daughter's health (8.4%). The main reasons for not having a daughter receive the HPV vaccine were concerns about HPV vaccine safety (29.2%), preference to wait until the daughter is older (15.6%), and not enough information to make an informed decision (12.6%). In multivariate analysis, overall attitudes to vaccines, the impact of the HPV vaccine on sexual practices, and childhood vaccine history were predictive of parents having a daughter receive the HPV vaccine in a

A population-based evaluation of a publicly funded, school-based HPV vaccine program in British Columbia, Canada: parental factors associated with HPV vaccine receipt.

Directory of Open Access Journals (Sweden)

Gina Ogilvie

2010-05-01

Full Text Available BACKGROUND: Information on factors that influence parental decisions for actual human papillomavirus (HPV vaccine receipt in publicly funded, school-based HPV vaccine programs for girls is limited. We report on the level of uptake of the first dose of the HPV vaccine, and determine parental factors associated with receipt of the HPV vaccine, in a publicly funded school-based HPV vaccine program in British Columbia, Canada. METHODS AND FINDINGS: All parents of girls enrolled in grade 6 during the academic year of September 2008-June 2009 in the province of British Columbia were eligible to participate. Eligible households identified through the provincial public health information system were randomly selected and those who consented completed a validated survey exploring factors associated with HPV vaccine uptake. Bivariate and multivariate analyses were conducted to calculate adjusted odds ratios to identify the factors that were associated with parents' decision to vaccinate their daughter(s against HPV. 2,025 parents agreed to complete the survey, and 65.1% (95% confidence interval [CI] 63.1-67.1 of parents in the survey reported that their daughters received the first dose of the HPV vaccine. In the same school-based vaccine program, 88.4% (95% CI 87.1-89.7 consented to the hepatitis B vaccine, and 86.5% (95% CI 85.1-87.9 consented to the meningococcal C vaccine. The main reasons for having a daughter receive the HPV vaccine were the effectiveness of the vaccine (47.9%, advice from a physician (8.7%, and concerns about daughter's health (8.4%. The main reasons for not having a daughter receive the HPV vaccine were concerns about HPV vaccine safety (29.2%, preference to wait until the daughter is older (15.6%, and not enough information to make an informed decision (12.6%. In multivariate analysis, overall attitudes to vaccines, the impact of the HPV vaccine on sexual practices, and childhood vaccine history were predictive of parents having

Particle-based vaccines for HIV-1 infection.

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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.

A history of adolescent school based vaccination in Australia.

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Ward, Kirsten; Quinn, Helen; Menzies, Robert; McIntyre, Peter

2013-06-30

As adolescents have become an increasingly prominent target group for vaccination, school-based vaccination has emerged as an efficient and effective method of delivering nationally recommended vaccines to this often hard to reach group. School-based delivery of vaccines has occurred in Australia for over 80 years and has demonstrated advantages over primary care delivery for this part of the population. In the last decade school-based vaccination programs have become routine practice across all Australian states and territories. Using existing records and the recollection of experts we have compiled a history of school-based vaccination in Australia, primarily focusing on adolescents. This work is copyright. Apart from any use as permitted under the Copyright Act 1968, no part may be reproduced by any process without prior written permission from the Commonwealth. Requests and inquiries concerning reproduction and rights should be addressed to the Commonwealth Copyright Administration, Attorney General's Department, Robert Garran Offices, National Circuit, Barton ACT 2600 or posted at http://www.ag.gov.au/cca.

New Kids on the Block: RNA-Based Influenza Virus Vaccines.

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Scorza, Francesco Berlanda; Pardi, Norbert

2018-04-01

RNA-based immunization strategies have emerged as promising alternatives to conventional vaccine approaches. A substantial body of published work demonstrates that RNA vaccines can elicit potent, protective immune responses against various pathogens. Consonant with its huge impact on public health, influenza virus is one of the best studied targets of RNA vaccine research. Currently licensed influenza vaccines show variable levels of protection against seasonal influenza virus strains but are inadequate against drifted and pandemic viruses. In recent years, several types of RNA vaccines demonstrated efficacy against influenza virus infections in preclinical models. Additionally, comparative studies demonstrated the superiority of some RNA vaccines over the currently used inactivated influenza virus vaccines in animal models. Based on these promising preclinical results, clinical trials have been initiated and should provide valuable information about the translatability of the impressive preclinical data to humans. This review briefly describes RNA-based vaccination strategies, summarizes published preclinical and clinical data, highlights the roadblocks that need to be overcome for clinical applications, discusses the landscape of industrial development, and shares the authors' personal perspectives about the future of RNA-based influenza virus vaccines.

NIGERIAN VETERINARY JOURNAL

African Journals Online (AJOL)

ADEYEYE

Fowlpox Virus from Backyard Poultry in Plateau State Nigeria: Isolation and Phylogeny of the P4b Gene Compared to a Vaccine Strain. Meseko, C. A.. 1. ; Shittu, I. 1. ; Bwala, D. G.. 2. ; Joannis, T. M.. 1 and Nwosuh, C. I.. 2. 1Regional Laboratory For Animal Influenza and Transboundary Animal Diseases, National Veterinary ...

Crystallization and preliminary X-ray crystallographic analysis of the rhesus macaque MHC class I molecule Mamu-B*17 complexed with an immunodominant SIVmac239 Env epitope

International Nuclear Information System (INIS)

Gao, Feng; Bao, Jinku

2013-01-01

A primitive monoclinic crystal of the rhesus macaque MHC class I molecule Mamu-B*17 complexed with an SIVmac239 Env peptide was obtained and belonged to space group P2, with unit-cell parameters a = 68.3, b = 45.0, c = 81.5 Å, β = 96.5°. The crystal diffracted to 2.55 Å resolution. Long-term nonprogression during simian immunodeficiency virus (SIV) infection has been strongly associated with the major histocompatibility complex (MHC) class I allele Mamu-B*17. Here, a complex of rhesus macaque Mamu-B*17 with rhesus macaque β 2 -microglobulin (β 2 m) and an immunodominant peptide (SIVmac239 Env241–251; LRCNDTNYSGF; Env LF11) derived from the SIV Env protein was crystallized by the hanging-drop method using PEG 3350 as a precipitating agent. The crystals belonged to the primitive monoclinic space group P2, with unit-cell parameters a = 68.3, b = 45.0, c = 81.5 Å, β = 96.5°. Assuming the presence of one molecule in the asymmetric unit, the Matthews coefficient and solvent content were calculated to be 2.96 Å 3 Da −1 and 58.5%, respectively

Animal vaccines based on orally presented yeast recombinants.

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Shin, Min-Kyoung; Yoo, Han Sang

2013-09-13

In veterinary vaccinology, the oral route of administration is an attractive alternative compared to the commonly used parenteral route. Yeasts have a number of properties that make them potential live delivery systems for oral vaccination purposes such as their high expression levels, their GRAS status, adjuvant properties, and post-translational modification possibilities. Consequently, yeasts have been employed for the expression of heterologous genes and for the production of therapeutic proteins. Yeast-based vaccines are reviewed with regard to their ability to express and produce antigens from pathogens for veterinary use. Many of these vaccines have been shown to elicit protective immune responses following oral immunization in animals. Ultimately, yeast-based oral vaccines may offer a potential opportunity for the development of novel ideal vaccines in veterinary medicine. Copyright © 2013 Elsevier Ltd. All rights reserved.

A thermostable messenger RNA based vaccine against rabies.

Science.gov (United States)

Stitz, Lothar; Vogel, Annette; Schnee, Margit; Voss, Daniel; Rauch, Susanne; Mutzke, Thorsten; Ketterer, Thomas; Kramps, Thomas; Petsch, Benjamin

2017-12-01

Although effective rabies virus vaccines have been existing for decades, each year, rabies virus infections still cause around 50.000 fatalities worldwide. Most of these cases occur in developing countries, where these vaccines are not available. The reasons for this are the prohibitive high costs of cell culture or egg grown rabies virus vaccines and the lack of a functional cold chain in many regions in which rabies virus is endemic. Here, we describe the excellent temperature resistance of a non-replicating mRNA based rabies virus vaccine encoding the rabies virus glycoprotein (RABV-G). Prolonged storage of the vaccine from -80°C to up to +70°C for several months did not impact the protective capacity of the mRNA vaccine. Efficacy after storage was demonstrated by the induction of rabies specific virus neutralizing antibodies and protection in mice against lethal rabies infection. Moreover, storing the vaccine at oscillating temperatures between +4° and +56°C for 20 cycles in order to simulate interruptions of the cold chain during vaccine transport, did not affect the vaccine's immunogenicity and protective characteristics, indicating that maintenance of a cold chain is not essential for this vaccine.

Strengthening vaccination policies in Latin America: an evidence-based approach.

Science.gov (United States)

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

Cabotegravir long acting injection protects macaques against intravenous challenge with SIVmac251.

Science.gov (United States)

Andrews, Chasity D; Bernard, Leslie St; Poon, Amanda Yee; Mohri, Hiroshi; Gettie, Natanya; Spreen, William R; Gettie, Agegnehu; Russell-Lodrigue, Kasi; Blanchard, James; Hong, Zhi; Ho, David D; Markowitz, Martin

2017-02-20

We evaluated the effectiveness of cabotegravir (CAB; GSK1265744 or GSK744) long acting as preexposure prophylaxis (PrEP) against intravenous simian immunodeficiency virus (SIV) challenge in a model that mimics blood transfusions based on the per-act probability of infection. CAB long acting is an integrase strand transfer inhibitor formulated as a 200 mg/ml injectable nanoparticle suspension that is an effective PrEP agent against rectal and vaginal simian/human immunodeficiency virus transmission in macaques. Three groups of rhesus macaques (n = 8 per group) were injected intramuscularly with CAB long acting and challenged intravenously with 17 animal infectious dose 50% SIVmac251 on week 2. Group 1 was injected with 50 mg/kg on week 0 and 4 to evaluate the protective efficacy of the CAB long-acting dose used in macaque studies mimicking sexual transmission. Group 2 was injected with 50 mg/kg on week 0 to evaluate the necessity of the second injection of CAB long acting for protection against intravenous challenge. Group 3 was injected with 25 mg/kg on week 0 and 50 mg/kg on week 4 to correlate CAB plasma concentrations at the time of challenge with protection. Five additional macaques remained untreated as controls. CAB long acting was highly protective with 21 of the 24 CAB long-acting-treated macaques remaining aviremic, resulting in 88% protection. The plasma CAB concentration at the time of virus challenge appeared to be more important for protection than sustaining therapeutic plasma concentrations with the second CAB long acting injection. These results support the clinical investigation of CAB long acting as PrEP in people who inject drugs.

Modified vaccinia virus ankara recombinants are as potent as vaccinia recombinants in diversified prime and boost vaccine regimens to elicit therapeutic antitumor responses.

Science.gov (United States)

Hodge, James W; Poole, Diane J; Aarts, Wilhelmina M; Gómez Yafal, Alicia; Gritz, Linda; Schlom, Jeffrey

2003-11-15

Cancer vaccine regimens use various strategies to enhance immune responses to specific tumor-associated antigens (TAAs), including the increasing use of recombinant poxviruses [vaccinia (rV) and fowlpox (rF)] for delivery of the TAA to the immune system. However, the use of replication competent vectors with the potential of adverse reactions have made attenuation a priority for next-generation vaccine strategies. Modified vaccinia Ankara (MVA) is a replication defective form of vaccinia virus. Here, we investigated the use of MVA encoding a tumor antigen gene, carcinoembryonic antigen (CEA), in addition to multiple costimulatory molecules (B7-1, intercellular adhesion molecule-1, and lymphocyte function-associated antigen-3 designated TRICOM). Vaccination of mice with MVA-CEA/TRICOM induced potent CD4+ and CD8+ T-cell responses specific for CEA. MVA-CEA/TRICOM could be administered twice in vaccinia naïve mice and only a single time in vaccinia-immune mice before being inhibited by antivector-immune responses. The use of MVA-CEA/TRICOM in a diversified prime and boost vaccine regimen with rF-CEA/TRICOM, however, induced significantly greater levels of both CD4+ and CD8+ T-cell responses specific for CEA than that seen with rV-CEA/TRICOM prime and rF-CEA/TRICOM boost. In a self-antigen tumor model, the diversified MVA-CEA/TRICOM/rF-CEA/ TRICOM vaccination regimen resulted in a significant therapeutic antitumor response as measured by increased survival, when compared with the diversified prime and boost regimen, rV-CEA/TRICOM/rF-CEA/TRICOM. The studies reported here demonstrate that MVA, when used as a prime in a diversified vaccination, is clearly comparable with the regimen using the recombinant vaccinia in both the induction of cellular immune responses specific for the "self"-TAA transgene and in antitumor activity.

Updates on the web-based VIOLIN vaccine database and analysis system.

Science.gov (United States)

He, Yongqun; Racz, Rebecca; Sayers, Samantha; Lin, Yu; Todd, Thomas; Hur, Junguk; Li, Xinna; Patel, Mukti; Zhao, Boyang; Chung, Monica; Ostrow, Joseph; Sylora, Andrew; Dungarani, Priya; Ulysse, Guerlain; Kochhar, Kanika; Vidri, Boris; Strait, Kelsey; Jourdian, George W; Xiang, Zuoshuang

2014-01-01

The integrative Vaccine Investigation and Online Information Network (VIOLIN) vaccine research database and analysis system (http://www.violinet.org) curates, stores, analyses and integrates various vaccine-associated research data. Since its first publication in NAR in 2008, significant updates have been made. Starting from 211 vaccines annotated at the end of 2007, VIOLIN now includes over 3240 vaccines for 192 infectious diseases and eight noninfectious diseases (e.g. cancers and allergies). Under the umbrella of VIOLIN, >10 relatively independent programs are developed. For example, Protegen stores over 800 protective antigens experimentally proven valid for vaccine development. VirmugenDB annotated over 200 'virmugens', a term coined by us to represent those virulence factor genes that can be mutated to generate successful live attenuated vaccines. Specific patterns were identified from the genes collected in Protegen and VirmugenDB. VIOLIN also includes Vaxign, the first web-based vaccine candidate prediction program based on reverse vaccinology. VIOLIN collects and analyzes different vaccine components including vaccine adjuvants (Vaxjo) and DNA vaccine plasmids (DNAVaxDB). VIOLIN includes licensed human vaccines (Huvax) and veterinary vaccines (Vevax). The Vaccine Ontology is applied to standardize and integrate various data in VIOLIN. VIOLIN also hosts the Ontology of Vaccine Adverse Events (OVAE) that logically represents adverse events associated with licensed human vaccines.

Prospects of HA-Based Universal Influenza Vaccine

Directory of Open Access Journals (Sweden)

Anwar M. Hashem

2015-01-01

Full Text Available Current influenza vaccines afford substantial protection in humans by inducing strain-specific neutralizing antibodies (Abs. Most of these Abs target highly variable immunodominant epitopes in the globular domain of the viral hemagglutinin (HA. Therefore, current vaccines may not be able to induce heterosubtypic immunity against the divergent influenza subtypes. The identification of broadly neutralizing Abs (BnAbs against influenza HA using recent technological advancements in antibody libraries, hybridoma, and isolation of single Ab-secreting plasma cells has increased the interest in developing a universal influenza vaccine as it could provide life-long protection. While these BnAbs can serve as a source for passive immunotherapy, their identification represents an important step towards the design of such a universal vaccine. This review describes the recent advances and approaches used in the development of universal influenza vaccine based on highly conserved HA regions identified by BnAbs.

Convergent evolution of SIV env after independent inoculation of rhesus macaques with infectious proviral DNA

International Nuclear Information System (INIS)

Buckley, Kathleen A.; Li Peilin; Khimani, Anis H.; Hofmann-Lehmann, Regina; Liska, Vladimir; Anderson, Daniel C.; McClure, Harold M.; Ruprecht, Ruth M.

2003-01-01

The env gene of three simian immunodeficiency virus (SIV) variants developed convergent mutations during disease progression in six rhesus macaques. The monkeys had been inoculated with supercoiled plasmids encoding infectious proviruses of SIVmac239 (a pathogenic, wild-type strain), SIVΔ3 (the live attenuated vaccine strain derived from SIVmac239), or SIVΔ3+ (a pathogenic progeny virus that had evolved from SIVΔ3). All six monkeys developed immunodeficiency and progressed to fatal disease. Although many divergent mutations arose in env among the different hosts, three regions consistently mutated in all monkeys studied; these similar mutations developed independently even though the animals had received only a single infectious molecular clone rather than standard viral inocula that contain viral quasispecies. Together, these data indicate that the env genes of SIVmac239, SIVΔ3, and SIVΔ3+, in the context of different proviral backbones, evolve similarly in different hosts during disease progression

Recombinant and epitope-based vaccines on the road to the market and implications for vaccine design and production.

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Oyarzún, Patricio; Kobe, Bostjan

2016-03-03

Novel vaccination approaches based on rational design of B- and T-cell epitopes - epitope-based vaccines - are making progress in the clinical trial pipeline. The epitope-focused recombinant protein-based malaria vaccine (termed RTS,S) is a next-generation approach that successfully reached phase-III trials, and will potentially become the first commercial vaccine against a human parasitic disease. Progress made on methods such as recombinant DNA technology, advanced cell-culture techniques, immunoinformatics and rational design of immunogens are driving the development of these novel concepts. Synthetic recombinant proteins comprising both B- and T-cell epitopes can be efficiently produced through modern biotechnology and bioprocessing methods, and can enable the induction of large repertoires of immune specificities. In particular, the inclusion of appropriate CD4+ T-cell epitopes is increasingly considered a key vaccine component to elicit robust immune responses, as suggested by results coming from HIV-1 clinical trials. In silico strategies for vaccine design are under active development to address genetic variation in pathogens and several broadly protective "universal" influenza and HIV-1 vaccines are currently at different stages of clinical trials. Other methods focus on improving population coverage in target populations by rationally considering specificity and prevalence of the HLA proteins, though a proof-of-concept in humans has not been demonstrated yet. Overall, we expect immunoinformatics and bioprocessing methods to become a central part of the next-generation epitope-based vaccine development and production process.

Ontology-Based Vaccine Adverse Event Representation and Analysis.

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Xie, Jiangan; He, Yongqun

2017-01-01

Vaccine is the one of the greatest inventions of modern medicine that has contributed most to the relief of human misery and the exciting increase in life expectancy. In 1796, an English country physician, Edward Jenner, discovered that inoculating mankind with cowpox can protect them from smallpox (Riedel S, Edward Jenner and the history of smallpox and vaccination. Proceedings (Baylor University. Medical Center) 18(1):21, 2005). Based on the vaccination worldwide, we finally succeeded in the eradication of smallpox in 1977 (Henderson, Vaccine 29:D7-D9, 2011). Other disabling and lethal diseases, like poliomyelitis and measles, are targeted for eradication (Bonanni, Vaccine 17:S120-S125, 1999).Although vaccine development and administration are tremendously successful and cost-effective practices to human health, no vaccine is 100% safe for everyone because each person reacts to vaccinations differently given different genetic background and health conditions. Although all licensed vaccines are generally safe for the majority of people, vaccinees may still suffer adverse events (AEs) in reaction to various vaccines, some of which can be serious or even fatal (Haber et al., Drug Saf 32(4):309-323, 2009). Hence, the double-edged sword of vaccination remains a concern.To support integrative AE data collection and analysis, it is critical to adopt an AE normalization strategy. In the past decades, different controlled terminologies, including the Medical Dictionary for Regulatory Activities (MedDRA) (Brown EG, Wood L, Wood S, et al., Drug Saf 20(2):109-117, 1999), the Common Terminology Criteria for Adverse Events (CTCAE) (NCI, The Common Terminology Criteria for Adverse Events (CTCAE). Available from: http://evs.nci.nih.gov/ftp1/CTCAE/About.html . Access on 7 Oct 2015), and the World Health Organization (WHO) Adverse Reactions Terminology (WHO-ART) (WHO, The WHO Adverse Reaction Terminology - WHO-ART. Available from: https://www.umc-products.com/graphics/28010.pdf

Use of an in vivo FTA assay to assess the magnitude, functional avidity and epitope variant cross-reactivity of T cell responses following HIV-1 recombinant poxvirus vaccination.

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Danushka K Wijesundara

Full Text Available Qualitative characteristics of cytotoxic CD8+ T cells (CTLs are important in measuring the effectiveness of CTLs in controlling HIV-1 infections. Indeed, in recent studies patients who are naturally resistant to HIV-1 infections have been shown to possess CTLs that are of high functional avidity and have a high capacity to recognize HIV epitope variants, when compared to HIV-1 infection progressors. When developing efficacious vaccines, assays that can effectively measure CTL quality specifically in vivo are becoming increasingly important. Here we report the use of a recently developed high-throughput multi-parameter technique, known as the fluorescent target array (FTA assay, to simultaneously measure CTL killing magnitude, functional avidity and epitope variant cross-reactivity in real time in vivo. In the current study we have applied the FTA assay as a screening tool to assess a large cohort of over 20 different HIV-1 poxvirus vaccination strategies in mice. This screen revealed that heterologous poxvirus prime-boost vaccination regimes (i.e., recombinant fowlpox (FPV-HIV prime followed by a recombinant vaccinia virus (VV-HIV booster were the most effective in generating high quality CTL responses in vivo. In conclusion, we have demonstrated how the FTA assay can be utilized as a cost effective screening tool (by reducing the required number of animals by >100 fold, to evaluate a large range of HIV-1 vaccination strategies in terms of CTL avidity and variant cross-reactivity in an in vivo setting.

Use of an in vivo FTA assay to assess the magnitude, functional avidity and epitope variant cross-reactivity of T cell responses following HIV-1 recombinant poxvirus vaccination.

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Wijesundara, Danushka K; Ranasinghe, Charani; Jackson, Ronald J; Lidbury, Brett A; Parish, Christopher R; Quah, Benjamin J C

2014-01-01

Qualitative characteristics of cytotoxic CD8+ T cells (CTLs) are important in measuring the effectiveness of CTLs in controlling HIV-1 infections. Indeed, in recent studies patients who are naturally resistant to HIV-1 infections have been shown to possess CTLs that are of high functional avidity and have a high capacity to recognize HIV epitope variants, when compared to HIV-1 infection progressors. When developing efficacious vaccines, assays that can effectively measure CTL quality specifically in vivo are becoming increasingly important. Here we report the use of a recently developed high-throughput multi-parameter technique, known as the fluorescent target array (FTA) assay, to simultaneously measure CTL killing magnitude, functional avidity and epitope variant cross-reactivity in real time in vivo. In the current study we have applied the FTA assay as a screening tool to assess a large cohort of over 20 different HIV-1 poxvirus vaccination strategies in mice. This screen revealed that heterologous poxvirus prime-boost vaccination regimes (i.e., recombinant fowlpox (FPV)-HIV prime followed by a recombinant vaccinia virus (VV)-HIV booster) were the most effective in generating high quality CTL responses in vivo. In conclusion, we have demonstrated how the FTA assay can be utilized as a cost effective screening tool (by reducing the required number of animals by >100 fold), to evaluate a large range of HIV-1 vaccination strategies in terms of CTL avidity and variant cross-reactivity in an in vivo setting.

Effect of plasma viremia on apoptosis and immunophenotype of dendritic cells subsets in acute SIVmac239 infection of Chinese rhesus macaques.

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Hou-Jun Xia

Full Text Available Non-human primates such as Chinese rhesus macaques (Ch Rhs provide good animal models for research on human infectious diseases. Similar to humans, there are two principal subsets of dendritic cells (DCs in the peripheral blood of Ch Rhs: myeloid DCs (mDCs and plasmacytoid DCs (pDCs. In this study, two-color fluorescence-activated cell sorting (FACS analyses were used to identify the main DC subsets, namely CD1c(+ mDCs and pDCs from Ch Rhs. Then, the apoptosis and immunophenotype changes of DCs subsets were first described during the acute phase of SIVmac239 infection. Both the DCs subsets showed decreased CD4 expression and enhanced CCR5 expression; in particular, those of pDCs significantly changed at most time points. Interestingly, the plasma viral loads were negatively correlated with CD4 expression, but were positively correlated with CCR5 expression of pDCs. During this period, both CD1c(+ mDCs and pDCs were activated by enhancing expressions of co-stimulatory molecules, accompanied with increase in CCR7. Either CD80 or CD86 expressed on CD1c(+ mDCs and pDCs was positively correlated with the plasma viral loads. Our analysis demonstrates that the pDCs were more prone to apoptosis after infection during the acute phase of SIVmac239 infection, which may be due to their high expressions of CD4 and CCR5. Both DCs subsets activated through elevating the expression of co-stimulatory molecules, which was beneficial in controlling the replication of SIV. However, a mere broad immune activation initiated by activated DCs may lead to tragic AIDS progression.

Parameter optimization toward optimal microneedle-based dermal vaccination.

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van der Maaden, Koen; Varypataki, Eleni Maria; Yu, Huixin; Romeijn, Stefan; Jiskoot, Wim; Bouwstra, Joke

2014-11-20

Microneedle-based vaccination has several advantages over vaccination by using conventional hypodermic needles. Microneedles are used to deliver a drug into the skin in a minimally-invasive and potentially pain free manner. Besides, the skin is a potent immune organ that is highly suitable for vaccination. However, there are several factors that influence the penetration ability of the skin by microneedles and the immune responses upon microneedle-based immunization. In this study we assessed several different microneedle arrays for their ability to penetrate ex vivo human skin by using trypan blue and (fluorescently or radioactively labeled) ovalbumin. Next, these different microneedles and several factors, including the dose of ovalbumin, the effect of using an impact-insertion applicator, skin location of microneedle application, and the area of microneedle application, were tested in vivo in mice. The penetration ability and the dose of ovalbumin that is delivered into the skin were shown to be dependent on the use of an applicator and on the microneedle geometry and size of the array. Besides microneedle penetration, the above described factors influenced the immune responses upon microneedle-based vaccination in vivo. It was shown that the ovalbumin-specific antibody responses upon microneedle-based vaccination could be increased up to 12-fold when an impact-insertion applicator was used, up to 8-fold when microneedles were applied over a larger surface area, and up to 36-fold dependent on the location of microneedle application. Therefore, these influencing factors should be considered to optimize microneedle-based dermal immunization technologies. Copyright © 2014 Elsevier B.V. All rights reserved.

Content of web-based continuing medical education about HPV vaccination.

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Kornides, Melanie L; Garrell, Jacob M; Gilkey, Melissa B

2017-08-16

Addressing low HPV vaccination coverage will require U.S. health care providers to improve their recommendation practices and vaccine delivery systems. Because readily available continuing medical education (CME) could be an important tool for supporting providers in this process, we sought to assess the content of web-based CME activities related to HPV vaccination. We conducted a content analysis of web-based CME activities about HPV vaccination available to U.S. primary care providers in May-September 2016. Using search engines, educational clearinghouses, and our professional networks, we identified 15 activities eligible for study inclusion. Through a process of open coding, we identified 45 commonly occurring messages in the CME activities, which we organized into five topic areas: delivering recommendations for HPV vaccination, addressing common parent concerns, implementing office-based strategies to increase HPV vaccination coverage, HPV epidemiology, and guidelines for HPV vaccine administration and safety. Using a standardized abstraction form, two coders then independently assessed which of the 45 messages each CME activity included. CME activities varied in the amount of content they delivered, with inclusion of the 45 messages ranging from 17% to 86%. Across activities, the most commonly included messages were related to guidelines for HPV vaccine administration and safety. For example, all activities (100%) specified that routine administration is recommended for ages 11 and 12. Most activities (73%) also noted that provider recommendations are highly influential. Fewer activities modeled examples of effective recommendations (47%), gave specific approaches to addressing common parent concerns (47%), or included guidance on office-based strategies to increase coverage (40%). Given that many existing CME activities lack substantive content on how to change provider practice, future activities should focus on the practical application of interpersonal

Vaccination-challenge studies with a Port Chalmers/73 (H3N2)-based swine influenza virus vaccine: Reflections on vaccine strain updates and on the vaccine potency test.

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De Vleeschauwer, Annebel; Qiu, Yu; Van Reeth, Kristien

2015-05-11

The human A/Port Chalmers/1/73 (H3N2) influenza virus strain, the supposed ancestor of European H3N2 swine influenza viruses (SIVs), was used in most commercial SIV vaccines in Europe until recently. If manufacturers want to update vaccine strains, they have to perform laborious intratracheal (IT) challenge experiments and demonstrate reduced virus titres in the lungs of vaccinated pigs. We aimed to examine (a) the ability of a Port Chalmers/73-based commercial vaccine to induce cross-protection against a contemporary European H3N2 SIV and serologic cross-reaction against H3N2 SIVs from Europe and North America and (b) the validity of intranasal (IN) challenge and virus titrations of nasal swabs as alternatives for IT challenge and titrations of lung tissue in vaccine potency tests. Pigs were vaccinated with Suvaxyn Flu(®) and challenged by the IT or IN route with sw/Gent/172/08. Post-vaccination sera were examined in haemagglutination-inhibition assays against vaccine and challenge strains and additional H3N2 SIVs from Europe and North America, including an H3N2 variant virus. Tissues of the respiratory tract and nasal swabs were collected 3 days post challenge (DPCh) and from 0-7 DPCh, respectively, and examined by virus titration. Two vaccinations consistently induced cross-reactive antibodies against European H3N2 SIVs from 1998-2012, but minimal or undetectable antibody titres against North American viruses. Challenge virus titres in the lungs, trachea and nasal mucosa of the vaccinated pigs were significantly reduced after both IT and IN challenge. Yet the reduction of virus titres and nasal shedding was greater after IT challenge. The Port Chalmers/73-based vaccine still offered protection against a European H3N2 SIV isolated 35 years later and with only 86.9% amino acid homology in its HA1, but it is unlikely to protect against H3N2 SIVs that are endemic in North America. We use our data to reflect on vaccine strain updates and on the vaccine potency test

Vesicular stomatitis virus-based vaccines protect nonhuman primates against Bundibugyo ebolavirus.

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Chad E Mire

Full Text Available Ebola virus (EBOV causes severe and often fatal hemorrhagic fever in humans and nonhuman primates (NHPs. Currently, there are no licensed vaccines or therapeutics for human use. Recombinant vesicular stomatitis virus (rVSV-based vaccine vectors, which encode an EBOV glycoprotein in place of the VSV glycoprotein, have shown 100% efficacy against homologous Sudan ebolavirus (SEBOV or Zaire ebolavirus (ZEBOV challenge in NHPs. In addition, a single injection of a blend of three rVSV vectors completely protected NHPs against challenge with SEBOV, ZEBOV, the former Côte d'Ivoire ebolavirus, and Marburg virus. However, recent studies suggest that complete protection against the newly discovered Bundibugyo ebolavirus (BEBOV using several different heterologous filovirus vaccines is more difficult and presents a new challenge. As BEBOV caused nearly 50% mortality in a recent outbreak any filovirus vaccine advanced for human use must be able to protect against this new species. Here, we evaluated several different strategies against BEBOV using rVSV-based vaccines. Groups of cynomolgus macaques were vaccinated with a single injection of a homologous BEBOV vaccine, a single injection of a blended heterologous vaccine (SEBOV/ZEBOV, or a prime-boost using heterologous SEBOV and ZEBOV vectors. Animals were challenged with BEBOV 29-36 days after initial vaccination. Macaques vaccinated with the homologous BEBOV vaccine or the prime-boost showed no overt signs of illness and survived challenge. In contrast, animals vaccinated with the heterologous blended vaccine and unvaccinated control animals developed severe clinical symptoms consistent with BEBOV infection with 2 of 3 animals in each group succumbing. These data show that complete protection against BEBOV will likely require incorporation of BEBOV glycoprotein into the vaccine or employment of a prime-boost regimen. Fortunately, our results demonstrate that heterologous rVSV-based filovirus vaccine

Post-infection immunodeficiency virus control by neutralizing antibodies.

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Hiroyuki Yamamoto

sterile HIV protection by prophylactic vaccination has been suggested, this study points out a possibility of non-sterile HIV control by prophylactic vaccine-induced, sub-sterile titers of NAbs post-infection, providing a rationale of vaccine-based NAb induction for primary HIV control.

From non school-based, co-payment to school-based, free Human Papillomavirus vaccination in Flanders (Belgium): a retrospective cohort study describing vaccination coverage, age-specific coverage and socio-economic inequalities.

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Lefevere, Eva; Theeten, Heidi; Hens, Niel; De Smet, Frank; Top, Geert; Van Damme, Pierre

2015-09-22

School-based, free HPV vaccination for girls in the first year of secondary school was introduced in Flanders (Belgium) in 2010. Before that, non school-based, co-payment vaccination for girls aged 12-18 was in place. We compared vaccination coverage, age-specific coverage and socio-economic inequalities in coverage - 3 important parameters contributing to the effectiveness of the vaccination programs - under both vaccination systems. We used retrospective administrative data from different sources. Our sample consisted of all female members of the National Alliance of Christian Mutualities born in 1995, 1996, 1998 or 1999 (N=66,664). For each vaccination system we described the cumulative proportion HPV vaccination initiation and completion over time. We used life table analysis to calculate age-specific rates of HPV vaccination initiation and completion. Analyses were done separately for higher income and low income groups. Under non school-based, co-payment vaccination the proportions HPV vaccination initiation and completion slowly rose over time. By age 17, the proportion HPV vaccination initiation/completion was 0.75 (95% CI 0.74-076)/0.66 (95% CI 0.65-0.67). The median age at vaccination initiation/completion was 14.4 years (95% CI 14.4-14.5)/15.4 years (95% CI 15.3-15.4). Socio-economic inequalities in coverage widened over time and with age. Under school-based, free vaccination rates of HPV vaccination initiation were substantially higher. By age 14,the proportion HPV vaccination initiation/completion was 0.90 (95% CI 0.90-0.90)/0.87 (95% CI 0.87-0.88). The median age at vaccination initiation/completion was 12.7 years (95% CI 12.7-12.7)/13.3 years (95% CI 13.3-13.3). Socio-economic inequalities in coverage and in age-specific coverage were substantially smaller. Copyright © 2015. Published by Elsevier Ltd.

Protection of macaques with diverse MHC genotypes against a heterologous SIV by vaccination with a deglycosylated live-attenuated SIV.

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Chie Sugimoto

Full Text Available HIV vaccine development has been hampered by issues such as undefined correlates of protection and extensive diversity of HIV. We addressed these issues using a previously established SIV-macaque model in which SIV mutants with deletions of multiple gp120 N-glycans function as potent live attenuated vaccines to induce near-sterile immunity against the parental pathogenic SIVmac239. In this study, we investigated the protective efficacy of these mutants against a highly pathogenic heterologous SIVsmE543-3 delivered intravenously to rhesus macaques with diverse MHC genotypes. All 11 vaccinated macaques contained the acute-phase infection with blood viral loads below the level of detection between 4 and 10 weeks postchallenge (pc, following a transient but marginal peak of viral replication at 2 weeks in only half of the challenged animals. In the chronic phase, seven vaccinees contained viral replication for over 80 weeks pc, while four did not. Neutralizing antibodies against challenge virus were not detected. Although overall levels of SIV specific T cell responses did not correlate with containment of acute and chronic viral replication, a critical role of cellular responses in the containment of viral replication was suggested. Emergence of viruses with altered fitness due to recombination between the vaccine and challenge viruses and increased gp120 glycosylation was linked to the failure to control SIV. These results demonstrate the induction of effective protective immune responses in a significant number of animals against heterologous virus by infection with deglycosylated attenuated SIV mutants in macaques with highly diverse MHC background. These findings suggest that broad HIV cross clade protection is possible, even in hosts with diverse genetic backgrounds. In summary, results of this study indicate that deglycosylated live-attenuated vaccines may provide a platform for the elucidation of correlates of protection needed for a

From non school-based, co-payment to school-based, free Human Papillomavirus vaccination in Flanders (Belgium): A retrospective cohort study describing vaccination coverage, age-specific coverage and socio-economic inequalities

OpenAIRE

Lefevere, Eva; Theeten, Heidi; Hens, Niel; De Smet, Frank; Top, Geert; Van Damme, Pierre

2015-01-01

School-based, free HPV vaccination for girls in the first year of secondary school was introduced in Flanders (Belgium) in 2010. Before that, non school-based, co-payment vaccination for girls aged 12-18 was in place. We compared vaccination coverage, age-specific coverage and socio-economic inequalities in coverage -3 important parameters contributing to the effectiveness of the vaccination programs - under both vaccination systems. We used retrospective administrative data from different so...

Respiratory nanoparticle-based vaccines and challenges associated with animal models and translation.

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Renukaradhya, Gourapura J; Narasimhan, Balaji; Mallapragada, Surya K

2015-12-10

Vaccine development has had a huge impact on human health. However, there is a significant need to develop efficacious vaccines for several existing as well as emerging respiratory infectious diseases. Several challenges need to be overcome to develop efficacious vaccines with translational potential. This review focuses on two aspects to overcome some barriers - 1) the development of nanoparticle-based vaccines, and 2) the choice of suitable animal models for respiratory infectious diseases that will allow for translation. Nanoparticle-based vaccines, including subunit vaccines involving synthetic and/or natural polymeric adjuvants and carriers, as well as those based on virus-like particles offer several key advantages to help overcome the barriers to effective vaccine development. These include the ability to deliver combinations of antigens, target the vaccine formulation to specific immune cells, enable cross-protection against divergent strains, act as adjuvants or immunomodulators, allow for sustained release of antigen, enable single dose delivery, and potentially obviate the cold chain. While mouse models have provided several important insights into the mechanisms of infectious diseases, they are often a limiting step in translation of new vaccines to the clinic. An overview of different animal models involved in vaccine research for respiratory infections, with advantages and disadvantages of each model, is discussed. Taken together, advances in nanotechnology, combined with the right animal models for evaluating vaccine efficacy, has the potential to revolutionize vaccine development for respiratory infections. Copyright © 2015 Elsevier B.V. All rights reserved.

Pre-vaccination care-seeking in females reporting severe adverse reactions to HPV vaccine. A registry based case-control study

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Mølbak, Kåre; Hansen, Niels Dalum; Valentiner-Branth, Palle

2016-01-01

to the DMA of suspected severe adverse reactions.We selected controls without reports of adverse reactions from the Danish vaccination registry and matched by year of vaccination, age of vaccination, and municipality, and obtained from the Danish National Patient Registry and The National Health Insurance...... vaccination programme has declined. The aim of the present study was to determine health care-seeking prior to the first HPV vaccination among females who suspected adverse reactions to HPV vaccine. Methods In this registry-based case-control study, we included as cases vaccinated females with reports...... Service Register the history of health care usage two years prior to the first vaccine. We analysed the data by logistic regression while adjusting for the matching variables. Results The study included 316 cases who received first HPV vaccine between 2006 and 2014. Age range of cases was 11 to 52 years...

An Overview on the Field of Micro- and Nanotechnologies for Synthetic Peptide-Based Vaccines

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Aiala Salvador

2011-01-01

Full Text Available The development of synthetic peptide-based vaccines has many advantages in comparison with vaccines based on live attenuated organisms, inactivated or killed organism, or toxins. Peptide-based vaccines cannot revert to a virulent form, allow a better conservation, and are produced more easily and safely. However, they generate a weaker immune response than other vaccines, and the inclusion of adjuvants and/or the use of vaccine delivery systems is almost always needed. Among vaccine delivery systems, micro- and nanoparticulated ones are attractive, because their particulate nature can increase cross-presentation of the peptide. In addition, they can be passively or actively targeted to antigen presenting cells. Furthermore, particulate adjuvants are able to directly activate innate immune system in vivo. Here, we summarize micro- and nanoparticulated vaccine delivery systems used in the field of synthetic peptide-based vaccines as well as strategies to increase their immunogenicity.

HPV vaccines: their pathology-based discovery, benefits, and adverse effects.

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Nicol, Alcina F; de Andrade, Cecilia V; Russomano, Fabio B; Rodrigues, Luana S L; Oliveira, Nathalia S; Provance, David William; Nuovo, Gerard J

2015-12-01

The discovery of the human papillomavirus (HPV) vaccine illustrates the power of in situ-based pathologic analysis in better understanding and curing diseases. The 2 available HPV vaccines have markedly reduced the incidence of cervical intraepithelial neoplasias, genital warts, and cervical cancer throughout the world. Concerns about HPV vaccine safety have led some physicians, health care officials, and parents to refuse providing the recommended vaccination to the target population. The aims of the study were to discuss the discovery of HPV vaccine and review scientific data related to measurable outcomes from the use of HPV vaccines. The strong type-specific immunity against HPV in humans has been known for more than 25 years. Multiple studies confirm the positive risk benefit of HPV vaccination with minimal documented adverse effects. The most common adverse effect, injection site pain, occurred in about 10% of girls and was less than the rate reported for other vaccines. Use of HPV vaccine should be expanded into more diverse populations, mainly in low-resource settings. Copyright © 2015 Elsevier Inc. All rights reserved.

Vaxvec: The first web-based recombinant vaccine vector database and its data analysis

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Deng, Shunzhou; Martin, Carly; Patil, Rasika; Zhu, Felix; Zhao, Bin; Xiang, Zuoshuang; He, Yongqun

2015-01-01

A recombinant vector vaccine uses an attenuated virus, bacterium, or parasite as the carrier to express a heterologous antigen(s). Many recombinant vaccine vectors and related vaccines have been developed and extensively investigated. To compare and better understand recombinant vectors and vaccines, we have generated Vaxvec (http://www.violinet.org/vaxvec), the first web-based database that stores various recombinant vaccine vectors and those experimentally verified vaccines that use these vectors. Vaxvec has now included 59 vaccine vectors that have been used in 196 recombinant vector vaccines against 66 pathogens and cancers. These vectors are classified to 41 viral vectors, 15 bacterial vectors, 1 parasitic vector, and 1 fungal vector. The most commonly used viral vaccine vectors are double-stranded DNA viruses, including herpesviruses, adenoviruses, and poxviruses. For example, Vaxvec includes 63 poxvirus-based recombinant vaccines for over 20 pathogens and cancers. Vaxvec collects 30 recombinant vector influenza vaccines that use 17 recombinant vectors and were experimentally tested in 7 animal models. In addition, over 60 protective antigens used in recombinant vector vaccines are annotated and analyzed. User-friendly web-interfaces are available for querying various data in Vaxvec. To support data exchange, the information of vaccine vectors, vaccines, and related information is stored in the Vaccine Ontology (VO). Vaxvec is a timely and vital source of vaccine vector database and facilitates efficient vaccine vector research and development. PMID:26403370

Efficient Vaccine Distribution Based on a Hybrid Compartmental Model.

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Zhiwen Yu

Full Text Available To effectively and efficiently reduce the morbidity and mortality that may be caused by outbreaks of emerging infectious diseases, it is very important for public health agencies to make informed decisions for controlling the spread of the disease. Such decisions must incorporate various kinds of intervention strategies, such as vaccinations, school closures and border restrictions. Recently, researchers have paid increased attention to searching for effective vaccine distribution strategies for reducing the effects of pandemic outbreaks when resources are limited. Most of the existing research work has been focused on how to design an effective age-structured epidemic model and to select a suitable vaccine distribution strategy to prevent the propagation of an infectious virus. Models that evaluate age structure effects are common, but models that additionally evaluate geographical effects are less common. In this paper, we propose a new SEIR (susceptible-exposed-infectious šC recovered model, named the hybrid SEIR-V model (HSEIR-V, which considers not only the dynamics of infection prevalence in several age-specific host populations, but also seeks to characterize the dynamics by which a virus spreads in various geographic districts. Several vaccination strategies such as different kinds of vaccine coverage, different vaccine releasing times and different vaccine deployment methods are incorporated into the HSEIR-V compartmental model. We also design four hybrid vaccination distribution strategies (based on population size, contact pattern matrix, infection rate and infectious risk for controlling the spread of viral infections. Based on data from the 2009-2010 H1N1 influenza epidemic, we evaluate the effectiveness of our proposed HSEIR-V model and study the effects of different types of human behaviour in responding to epidemics.

Oral Modeling of an Adenovirus-Based Quadrivalent Influenza Vaccine in Ferrets and Mice.

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Scallan, Ciaran D; Lindbloom, Jonathan D; Tucker, Sean N

2016-06-01

Oral vaccines delivered as tablets offer a number of advantages over traditional parenteral-based vaccines including the ease of delivery, lack of needles, no need for trained medical personnel, and the ability to formulate into temperature-stable tablets. We have been evaluating an oral vaccine platform based on recombinant adenoviral vectors for the purpose of creating a prophylactic vaccine to prevent influenza, and have demonstrated vaccine efficacy in animal models and substantial immunogenicity in humans. These studies have evaluated monovalent vaccines to date. To protect against the major circulating A and B influenza strains, a multivalent influenza vaccine will be required. In this study, the immunogenicity of orally delivered monovalent, bivalent, trivalent, and quadrivalent vaccines was tested in ferrets and mice. The various vaccine combinations were tested by blending monovalent recombinant adenovirus vaccines, each expressing hemagglutinin from a single strain. Human tablet delivery was modeled in animals by oral gavage in mice and by endoscopic delivery in ferrets. We demonstrated minimal interference between the various vaccine vectors when used in combination and that the oral quadrivalent vaccine compared favorably to an approved trivalent inactivated vaccine. The quadrivalent vaccine presented here produced immune responses that we predict should be capable of providing protection against multiple influenza strains, and the platform should have applications to other multivalent vaccines. Vaxart, Inc.

'It's a logistical nightmare!' Recommendations for optimising human papillomavirus school-based vaccination experience.

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Robbins, Spring Chenoa Cooper; Bernard, Diana; McCaffery, Kirsten; Skinner, S Rachel

2010-09-01

To date, no published studies examine procedural factors of the school-based human papillomavirus (HPV) vaccination program from the perspective of those involved. This study examines the factors that were perceived to impact optimal vaccination experience. Schools across Sydney were selected to reflect a range of vaccination coverage at the school level and different school types to ensure a range of experiences. Semi-structured focus groups were conducted with girls; and one-on-one interviews were undertaken with parents, teachers and nurses until saturation of data in all emergent themes was reached. Focus groups and interviews explored participants' experiences in school-based HPV vaccination. Transcripts were analysed, letting themes emerge. Themes related to participants' experience of the organisational, logistical and procedural aspects of the vaccination program and their perceptions of an optimal process were organised into two categories: (1) preparation for the vaccination program and (2) vaccination day strategies. In (1), themes emerged regarding commitment to the process from those involved, planning time and space for vaccinations, communication within and between agencies, and flexibility. In (2), themes included vaccinating the most anxious girls first, facilitating peer support, use of distraction techniques, minimising waiting time girls, and support staff. A range of views exists on what constitutes an optimal school-based program. Several findings were identified that should be considered in the development of guidelines for implementing school-based programs. Future research should evaluate how different approaches to acquiring parental consent, and the use of anxiety and fear reduction strategies impact experience and uptake in the school-based setting.

Clinical responses in patients with advanced colorectal cancer to a dendritic cell based vaccine

DEFF Research Database (Denmark)

Burgdorf, Stefan K; Fischer, Anders; Myschetzky, Peter S

2008-01-01

Patients with disseminated colorectal cancer have a poor prognosis. Preliminary studies have shown encouraging results from vaccines based on dendritic cells. The aim of this phase II study was to evaluate the effect of treating patients with advanced colorectal cancer with a cancer vaccine based...... with this DC-based cancer vaccine was safe and non-toxic. Stable disease was found in 24% (4/17) of the patients. The quality of life remained for most categories high and stable throughout the study period.......Patients with disseminated colorectal cancer have a poor prognosis. Preliminary studies have shown encouraging results from vaccines based on dendritic cells. The aim of this phase II study was to evaluate the effect of treating patients with advanced colorectal cancer with a cancer vaccine based......-testis antigens. Vaccines were biweekly administered intradermally with a total of 10 vaccines per patient. CT scans were performed and responses were graded according to the RECIST criteria. Quality of life was monitored with the SF-36 questionnaire. Toxicity and adverse events were graded according...

Trial watch: Naked and vectored DNA-based anticancer vaccines.

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Bloy, Norma; Buqué, Aitziber; Aranda, Fernando; Castoldi, Francesca; Eggermont, Alexander; Cremer, Isabelle; Sautès-Fridman, Catherine; Fucikova, Jitka; Galon, Jérôme; Spisek, Radek; Tartour, Eric; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

2015-05-01

One type of anticancer vaccine relies on the administration of DNA constructs encoding one or multiple tumor-associated antigens (TAAs). The ultimate objective of these preparations, which can be naked or vectored by non-pathogenic viruses, bacteria or yeast cells, is to drive the synthesis of TAAs in the context of an immunostimulatory milieu, resulting in the (re-)elicitation of a tumor-targeting immune response. In spite of encouraging preclinical results, the clinical efficacy of DNA-based vaccines employed as standalone immunotherapeutic interventions in cancer patients appears to be limited. Thus, efforts are currently being devoted to the development of combinatorial regimens that allow DNA-based anticancer vaccines to elicit clinically relevant immune responses. Here, we discuss recent advances in the preclinical and clinical development of this therapeutic paradigm.

Tipping the Proteome with Gene-Based Vaccines: Weighing in on the Role of Nano materials

International Nuclear Information System (INIS)

Flores, K.J.; Craig, M.; Smith, J.J.; DeLong, R.K.; Wanekaya, A.; Dong, L.

2012-01-01

Since the first generation of DNA vaccines was introduced in 1988, remarkable improvements have been made to improve their efficacy and immunogenicity. Although human clinical trials have shown that delivery of DNA vaccines is well tolerated and safe, the potency of these vaccines in humans is somewhat less than optimal. The development of a gene-based vaccine that was effective enough to be approved for clinical use in humans would be one of, if not the most important, advance in vaccines to date. This paper highlights the literature relating to gene-based vaccines, specifically DNA vaccines, and suggests possible approaches to boost their performance. In addition, we explore the idea that combining RNA and nano materials may hold the key to successful gene-based vaccines for prevention and treatment of disease

Dendritic cell-based vaccination in cancer: therapeutic implications emerging from murine models

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Soledad eMac Keon

2015-05-01

Full Text Available Dendritic cells (DCs play a pivotal role in the orchestration of immune responses, and are thus key targets in cancer vaccine design. Since the 2010 FDA approval of the first cancer DC-based vaccine (Sipuleucel T there has been a surge of interest in exploiting these cells as a therapeutic option for the treatment of tumors of diverse origin. In spite of the encouraging results obtained in the clinic, many elements of DC-based vaccination strategies need to be optimized. In this context, the use of experimental cancer models can help direct efforts towards an effective vaccine design. This paper reviews recent findings in murine models regarding the antitumoral mechanisms of DC-based vaccination, covering issues related to antigen sources, the use of adjuvants and maturing agents, and the role of DC subsets and their interaction in the initiation of antitumoral immune responses. The summary of such diverse aspects will highlight advantages and drawbacks in the use of murine models, and contribute to the design of successful DC-based translational approaches for cancer treatment.

Likelihood-based methods for evaluating principal surrogacy in augmented vaccine trials.

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Liu, Wei; Zhang, Bo; Zhang, Hui; Zhang, Zhiwei

2017-04-01

There is growing interest in assessing immune biomarkers, which are quick to measure and potentially predictive of long-term efficacy, as surrogate endpoints in randomized, placebo-controlled vaccine trials. This can be done under a principal stratification approach, with principal strata defined using a subject's potential immune responses to vaccine and placebo (the latter may be assumed to be zero). In this context, principal surrogacy refers to the extent to which vaccine efficacy varies across principal strata. Because a placebo recipient's potential immune response to vaccine is unobserved in a standard vaccine trial, augmented vaccine trials have been proposed to produce the information needed to evaluate principal surrogacy. This article reviews existing methods based on an estimated likelihood and a pseudo-score (PS) and proposes two new methods based on a semiparametric likelihood (SL) and a pseudo-likelihood (PL), for analyzing augmented vaccine trials. Unlike the PS method, the SL method does not require a model for missingness, which can be advantageous when immune response data are missing by happenstance. The SL method is shown to be asymptotically efficient, and it performs similarly to the PS and PL methods in simulation experiments. The PL method appears to have a computational advantage over the PS and SL methods.

Active SMS-based influenza vaccine safety surveillance in Australian children.

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Pillsbury, Alexis; Quinn, Helen; Cashman, Patrick; Leeb, Alan; Macartney, Kristine

2017-12-18

Australia's novel, active surveillance system, AusVaxSafety, monitors the post-market safety of vaccines in near real time. We analysed cumulative surveillance data for children aged 6 months to 4 years who received seasonal influenza vaccine in 2015 and/or 2016 to determine: adverse event following immunisation (AEFI) rates by vaccine brand, age and concomitant vaccine administration. Parent/carer reports of AEFI occurring within 3 days of their child receiving an influenza vaccine in sentinel immunisation clinics were solicited by Short Message Service (SMS) and/or email-based survey. Retrospective data from 2 years were combined to examine specific AEFI rates, particularly fever and medical attendance as a proxy for serious adverse events (SAE), with and without concomitant vaccine administration. As trivalent influenza vaccines (TIV) were funded in Australia's National Immunisation Program (NIP) in 2015 and quadrivalent (QIV) in 2016, respectively, we compared their safety profiles. 7402 children were included. Data were reported weekly through each vaccination season; no safety signals or excess of adverse events were detected. More children who received a concomitant vaccine had fever (7.5% versus 2.8%; p vaccine was associated with the highest increase in AEFI rates among children receiving a specified concomitant vaccine: 30.3% reported an AEFI compared with 7.3% who received an influenza vaccine alone (p safety profiles included low and expected AEFI rates (fever: 4.3% for TIV compared with 3.2% for QIV (p = .015); injection site reaction: 1.9% for TIV compared with 3.0% for QIV (p safety profile between brands. Active participant-reported data provided timely vaccine brand-specific safety information. Our surveillance system has particular utility in monitoring the safety of influenza vaccines, given that they may vary in composition annually. Copyright © 2017 Elsevier Ltd. All rights reserved.

Trivalent MDCK cell culture-derived influenza vaccine Optaflu (Novartis Vaccines).

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Doroshenko, Alexander; Halperin, Scott A

2009-06-01

Annual influenza epidemics continue to have a considerable impact in both developed and developing countries. Vaccination remains the principal measure to prevent seasonal influenza and reduce associated morbidity and mortality. The WHO recommends using established mammalian cell culture lines as an alternative to egg-based substrates in the manufacture of influenza vaccine. In June 2007, the EMEA approved Optaflu, a Madin Darby canine kidney cell culture-derived influenza vaccine manufactured by Novartis Vaccines. This review examines the advantages and disadvantages of cell culture-based technology for influenza vaccine production, compares immunogenicity and safety data for Optaflu with that of currently marketed conventional egg-based influenza vaccines, and considers the prospects for wider use of cell culture-based influenza vaccines.

Toolbox for non-intrusive structural and functional analysis of recombinant VLP based vaccines: a case study with hepatitis B vaccine.

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Anke M Mulder

Full Text Available BACKGROUND: Fundamental to vaccine development, manufacturing consistency, and product stability is an understanding of the vaccine structure-activity relationship. With the virus-like particle (VLP approach for recombinant vaccines gaining popularity, there is growing demand for tools that define their key characteristics. We assessed a suite of non-intrusive VLP epitope structure and function characterization tools by application to the Hepatitis B surface antigen (rHBsAg VLP-based vaccine. METHODOLOGY: The epitope-specific immune reactivity of rHBsAg epitopes to a given monoclonal antibody was monitored by surface plasmon resonance (SPR and quantitatively analyzed on rHBsAg VLPs in-solution or bound to adjuvant with a competitive enzyme-linked immunosorbent assay (ELISA. The structure of recombinant rHBsAg particles was examined by cryo transmission electron microscopy (cryoTEM and in-solution atomic force microscopy (AFM. PRINCIPAL FINDINGS: SPR and competitive ELISA determined relative antigenicity in solution, in real time, with rapid turn-around, and without the need of dissolving the particulate aluminum based adjuvant. These methods demonstrated the nature of the clinically relevant epitopes of HBsAg as being responsive to heat and/or redox treatment. In-solution AFM and cryoTEM determined vaccine particle size distribution, shape, and morphology. Redox-treated rHBsAg enabled 3D reconstruction from CryoTEM images--confirming the previously proposed octahedral structure and the established lipid-to-protein ratio of HBsAg particles. Results from these non-intrusive biophysical and immunochemical analyses coalesced into a comprehensive understanding of rHBsAg vaccine epitope structure and function that was important for assuring the desired epitope formation, determinants for vaccine potency, and particle stability during vaccine design, development, and manufacturing. SIGNIFICANCE: Together, the methods presented here comprise a novel

Nucleic acid-based vaccines targeting respiratory syncytial virus: Delivering the goods.

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Smith, Trevor R F; Schultheis, Katherine; Broderick, Kate E

2017-11-02

Respiratory syncytial virus (RSV) is a massive medical burden on a global scale. Infants, children and the elderly represent the vulnerable populations. Currently there is no approved vaccine to protect against the disease. Vaccine development has been hindered by several factors including vaccine enhanced disease (VED) associated with formalin-inactivated RSV vaccines, inability of target populations to raise protective immune responses after vaccination or natural viral infection, and a lack of consensus concerning the most appropriate virus-associated target antigen. However, with recent advances in the molecular understanding of the virus, and design of highly characterized vaccines with enhanced immunogenicity there is new belief a RSV vaccine is possible. One promising approach is nucleic acid-based vaccinology. Both DNA and mRNA RSV vaccines are showing promising results in clinically relevant animal models, supporting their transition into humans. Here we will discuss this strategy to target RSV, and the ongoing studies to advance the nucleic acid vaccine platform as a viable option to protect vulnerable populations from this important disease.

Clarification of vaccines: An overview of filter based technology trends and best practices.

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Besnard, Lise; Fabre, Virginie; Fettig, Michael; Gousseinov, Elina; Kawakami, Yasuhiro; Laroudie, Nicolas; Scanlan, Claire; Pattnaik, Priyabrata

2016-01-01

Vaccines are derived from a variety of sources including tissue extracts, bacterial cells, virus particles, recombinant mammalian, yeast and insect cell produced proteins and nucleic acids. The most common method of vaccine production is based on an initial fermentation process followed by purification. Production of vaccines is a complex process involving many different steps and processes. Selection of the appropriate purification method is critical to achieving desired purity of the final product. Clarification of vaccines is a critical step that strongly impacts product recovery and subsequent downstream purification. There are several technologies that can be applied for vaccine clarification. Selection of a harvesting method and equipment depends on the type of cells, product being harvested, and properties of the process fluids. These techniques include membrane filtration (microfiltration, tangential-flow filtration), centrifugation, and depth filtration (normal flow filtration). Historically vaccine harvest clarification was usually achieved by centrifugation followed by depth filtration. Recently membrane based technologies have gained prominence in vaccine clarification. The increasing use of single-use technologies in upstream processes necessitated a shift in harvest strategies. This review offers a comprehensive view on different membrane based technologies and their application in vaccine clarification, outlines the challenges involved and presents the current state of best practices in the clarification of vaccines. Copyright © 2015 Elsevier Inc. All rights reserved.

Recombinant allergy vaccines based on allergen-derived B cell epitopes.

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Valenta, Rudolf; Campana, Raffaela; Niederberger, Verena

2017-09-01

Immunoglobulin E (IgE)-associated allergy is the most common immunologically-mediated hypersensitivity disease. It affects more than 25% of the population. In IgE-sensitized subjects, allergen encounter can causes a variety of symptoms ranging from hayfever (allergic rhinoconjunctivitis) to asthma, skin inflammation, food allergy and severe life-threatening anaphylactic shock. Allergen-specific immunotherapy (AIT) is based on vaccination with the disease-causing allergens. AIT is an extremely effective, causative and disease-modifying treatment. However, administration of natural allergens can cause severe side effects and the quality of natural allergen extracts limits its application. Research in the field of molecular allergen characterization has allowed deciphering the molecular structures of the disease-causing allergens and it has become possible to engineer novel molecular allergy vaccines which precisely target the mechanisms of the allergic immune response and even appear suitable for prophylactic allergy vaccination. Here we discuss recombinant allergy vaccines which are based on allergen-derived B cell epitopes regarding their molecular and immunological properties and review the results obtained in clinical studies with this new type of allergy vaccines. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

School-based influenza vaccination: parents' perspectives.

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Candace Lind

Full Text Available School-age children are important drivers of annual influenza epidemics yet influenza vaccination coverage of this population is low despite universal publicly funded influenza vaccination in Alberta, Canada. Immunizing children at school may potentially increase vaccine uptake. As parents are a key stakeholder group for such a program, it is important to consider their concerns.We explored parents' perspectives on the acceptability of adding an annual influenza immunization to the immunization program that is currently delivered in Alberta schools, and obtained suggestions for structuring such a program.Forty-eight parents of children aged 5-18 years participated in 9 focus groups. Participants lived in urban areas of the Alberta Health Services Calgary Zone.Three major themes emerged: Advantages of school-based influenza vaccination (SBIV, Disadvantages of SBIV, and Implications for program design & delivery. Advantages were perceived to occur for different populations: children (e.g. emotional support, families (e.g. convenience, the community (e.g. benefits for school and multicultural communities, the health sector (e.g. reductions in costs due to burden of illness and to society at large (e.g. indirect conduit of information about health services, building structure for pandemic preparedness, building healthy lifestyles. Disadvantages, however, might also occur for children (e.g. older children less likely to be immunized, families (e.g. communication challenges, perceived loss of parental control over information, choices and decisions and the education sector (loss of instructional time. Nine second-level themes emerged within the major theme of Implications for program design & delivery: program goals/objectives, consent process, stakeholder consultation, age-appropriate program, education, communication, logistics, immunizing agent, and clinic process.Parents perceived advantages and disadvantages to delivering annual seasonal

Enhanced protection against Ebola virus mediated by an improved adenovirus-based vaccine.

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Richardson, Jason S; Yao, Michel K; Tran, Kaylie N; Croyle, Maria A; Strong, James E; Feldmann, Heinz; Kobinger, Gary P

2009-01-01

The Ebola virus is transmitted by direct contact with bodily fluids of infected individuals, eliciting death rates as high as 90% among infected humans. Currently, replication defective adenovirus-based Ebola vaccine is being studied in a phase I clinical trial. Another Ebola vaccine, based on an attenuated vesicular stomatitis virus has shown efficacy in post-exposure treatment of nonhuman primates to Ebola infection. In this report, we modified the common recombinant adenovirus serotype 5-based Ebola vaccine expressing the wild-type ZEBOV glycoprotein sequence from a CMV promoter (Ad-CMVZGP). The immune response elicited by this improved expression cassette vector (Ad-CAGoptZGP) and its ability to afford protection against lethal ZEBOV challenge in mice was compared to the standard Ad-CMVZGP vector. Ad-CMVZGP was previously shown to protect mice, guinea pigs and nonhuman primates from an otherwise lethal challenge of Zaire ebolavirus. The antigenic expression cassette of this vector was improved through codon optimization, inclusion of a consensus Kozak sequence and reconfiguration of a CAG promoter (Ad-CAGoptZGP). Expression of GP from Ad-CAGoptZGP was substantially higher than from Ad-CMVZGP. Ad-CAGoptZGP significantly improved T and B cell responses at doses 10 to 100-fold lower than that needed with Ad-CMVZGP. Additionally, Ad-CAGoptZGP afforded full protections in mice against lethal challenge at a dose 100 times lower than the dose required for Ad-CMVZGP. Finally, Ad-CAGoptZGP induced full protection to mice when given 30 minutes post-challenge. We describe an improved adenovirus-based Ebola vaccine capable of affording post-exposure protection against lethal challenge in mice. The molecular modifications of the new improved vaccine also translated in the induction of significantly enhanced immune responses and complete protection at a dose 100 times lower than with the previous generation adenovirus-based Ebola vaccine. Understanding and improving the

Enhanced protection against Ebola virus mediated by an improved adenovirus-based vaccine.

Directory of Open Access Journals (Sweden)

Jason S Richardson

Full Text Available BACKGROUND: The Ebola virus is transmitted by direct contact with bodily fluids of infected individuals, eliciting death rates as high as 90% among infected humans. Currently, replication defective adenovirus-based Ebola vaccine is being studied in a phase I clinical trial. Another Ebola vaccine, based on an attenuated vesicular stomatitis virus has shown efficacy in post-exposure treatment of nonhuman primates to Ebola infection. In this report, we modified the common recombinant adenovirus serotype 5-based Ebola vaccine expressing the wild-type ZEBOV glycoprotein sequence from a CMV promoter (Ad-CMVZGP. The immune response elicited by this improved expression cassette vector (Ad-CAGoptZGP and its ability to afford protection against lethal ZEBOV challenge in mice was compared to the standard Ad-CMVZGP vector. METHODOLOGY/PRINCIPAL FINDINGS: Ad-CMVZGP was previously shown to protect mice, guinea pigs and nonhuman primates from an otherwise lethal challenge of Zaire ebolavirus. The antigenic expression cassette of this vector was improved through codon optimization, inclusion of a consensus Kozak sequence and reconfiguration of a CAG promoter (Ad-CAGoptZGP. Expression of GP from Ad-CAGoptZGP was substantially higher than from Ad-CMVZGP. Ad-CAGoptZGP significantly improved T and B cell responses at doses 10 to 100-fold lower than that needed with Ad-CMVZGP. Additionally, Ad-CAGoptZGP afforded full protections in mice against lethal challenge at a dose 100 times lower than the dose required for Ad-CMVZGP. Finally, Ad-CAGoptZGP induced full protection to mice when given 30 minutes post-challenge. CONCLUSIONS/SIGNIFICANCE: We describe an improved adenovirus-based Ebola vaccine capable of affording post-exposure protection against lethal challenge in mice. The molecular modifications of the new improved vaccine also translated in the induction of significantly enhanced immune responses and complete protection at a dose 100 times lower than with the

Using Dynamic Transmission Modeling to Determine Vaccination Coverage Rate Based on 5-Year Economic Burden of Infectious Disease: An Example of Pneumococcal Vaccine.

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Wen, Yu-Wen; Wu, Hsin; Chang, Chee-Jen

2015-05-01

Vaccination can reduce the incidence and mortality of an infectious disease and thus increase the years of life and productivity for the entire society. But when determining the vaccination coverage rate, its economic burden is usually not taken into account. This article aimed to use a dynamic transmission modeling (DTM), which is based on a susceptible-infectious-recovered model and is a system of differential equations, to find the optimal vaccination coverage rate based on the economic burden of an infectious disease. Vaccination for pneumococcal diseases was used as an example to demonstrate the main purpose. 23-Valent pneumococcal polysaccharide vaccines (PPV23) and 13-valent pneumococcal conjugate vaccines (PCV13) have shown their cost-effectiveness in elderly and children, respectively. Scenarios analysis of PPV23 to elderly aged 65+ years and of PCV13 to children aged 0 to 4 years was applied to assess the optimal vaccination coverage rate based on the 5-year economic burden. Model parameters were derived from Taiwan's National Health Insurance Research Database, government data, and published literature. Various vaccination coverage rates, the vaccine efficacy, and all epidemiologic parameters were substituted into DTM, and all differential equations were solved in R Statistical Software. If the coverage rate of PPV23 for the elderly and of PCV13 for the children both reach 50%, the economic burden due to pneumococcal disease will be acceptable. This article provided an alternative perspective from the economic burden of diseases to obtain a vaccination coverage rate using the DTM. This will provide valuable information for vaccination policy decision makers. Copyright © 2015 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

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

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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.

Changes in soluble factor-mediated CD8+ cell-derived antiviral activity in cynomolgus macaques infected with simian immunodeficiency virus SIVmac251: relationship to biological markers of progression.

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Dioszeghy, Vincent; Benlhassan-Chahour, Kadija; Delache, Benoit; Dereuddre-Bosquet, Nathalie; Aubenque, Celine; Gras, Gabriel; Le Grand, Roger; Vaslin, Bruno

2006-01-01

Cross-sectional studies have shown that the capacity of CD8+ cells from human immunodeficiency virus (HIV)-infected patients and simian immunodeficiency virus (SIV) SIVmac-infected macaques to suppress the replication of human and simian immunodeficiency viruses in vitro depends on the clinical stage of disease, but little is known about changes in this antiviral activity over time in individual HIV-infected patients or SIV-infected macaques. We assessed changes in the soluble factor-mediated noncytolytic antiviral activity of CD8+ cells over time in eight cynomolgus macaques infected with SIVmac251 to determine the pathophysiological role of this activity. CD8+ cell-associated antiviral activity increased rapidly in the first week after viral inoculation and remained detectable during the early phase of infection. The net increase in antiviral activity of CD8+ cells was correlated with plasma viral load throughout the 15 months of follow-up. CD8+ cells gradually lost their antiviral activity over time and acquired virus replication-enhancing capacity. Levels of antiviral activity correlated with CD4+ T-cell counts after viral set point. Concentrations of beta-chemokines and interleukin-16 in CD8+ cell supernatants were not correlated with this antiviral activity, and alpha-defensins were not detected. The soluble factor-mediated antiviral activity of CD8+ cells was neither cytolytic nor restricted to major histocompatibility complex. This longitudinal study strongly suggests that the increase in noncytolytic antiviral activity from baseline and the maintenance of this increase over time in cynomolgus macaques depend on both viral replication and CD4+ T cells.

Changes in Soluble Factor-Mediated CD8+ Cell-Derived Antiviral Activity in Cynomolgus Macaques Infected with Simian Immunodeficiency Virus SIVmac251: Relationship to Biological Markers of Progression†

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Dioszeghy, Vincent; Benlhassan-Chahour, Kadija; Delache, Benoit; Dereuddre-Bosquet, Nathalie; Aubenque, Celine; Gras, Gabriel; Le Grand, Roger; Vaslin, Bruno

2006-01-01

Cross-sectional studies have shown that the capacity of CD8+ cells from human immunodeficiency virus (HIV)-infected patients and simian immunodeficiency virus (SIV) SIVmac-infected macaques to suppress the replication of human and simian immunodeficiency viruses in vitro depends on the clinical stage of disease, but little is known about changes in this antiviral activity over time in individual HIV-infected patients or SIV-infected macaques. We assessed changes in the soluble factor-mediated noncytolytic antiviral activity of CD8+ cells over time in eight cynomolgus macaques infected with SIVmac251 to determine the pathophysiological role of this activity. CD8+ cell-associated antiviral activity increased rapidly in the first week after viral inoculation and remained detectable during the early phase of infection. The net increase in antiviral activity of CD8+ cells was correlated with plasma viral load throughout the 15 months of follow-up. CD8+ cells gradually lost their antiviral activity over time and acquired virus replication-enhancing capacity. Levels of antiviral activity correlated with CD4+ T-cell counts after viral set point. Concentrations of β-chemokines and interleukin-16 in CD8+ cell supernatants were not correlated with this antiviral activity, and α-defensins were not detected. The soluble factor-mediated antiviral activity of CD8+ cells was neither cytolytic nor restricted to major histocompatibility complex. This longitudinal study strongly suggests that the increase in noncytolytic antiviral activity from baseline and the maintenance of this increase over time in cynomolgus macaques depend on both viral replication and CD4+ T cells. PMID:16352548

Influenza during pregnancy: Incidence, vaccination coverage and attitudes toward vaccination in the French web-based cohort G-GrippeNet.

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Loubet, Paul; Guerrisi, Caroline; Turbelin, Clément; Blondel, Béatrice; Launay, Odile; Bardou, Marc; Goffinet, François; Colizza, Vittoria; Hanslik, Thomas; Kernéis, Solen

2016-04-29

Pregnancy is a risk factor for severe influenza. However, data on influenza incidence during pregnancy are scarce. Likewise, no data are available on influenza vaccine coverage in France since national recommendation in 2012. We aimed to assess these points using a novel nationwide web-based surveillance system, G-GrippeNet. During the 2014/2015 influenza season, pregnant women living in metropolitan France were enrolled through a web platform (https://www.grippenet.fr/). Throughout the season, participants were asked to report, on a weekly basis, if they had experienced symptoms of influenza-like-illness (ILI). ILI episodes reported were used to calculate incidence density rates based on period of participation from each participant. Vaccination coverage was estimated after weighing on age and education level from national data on pregnant women. Factors associated with higher vaccination coverage were obtained through a logistic regression with Odds Ratio (OR) corrected with the Zhang and Yu method. A total of 153 women were enrolled. ILI incidence density rate was 1.8 per 100 person-week (95% CI, 1.5-2.1). This rate was higher in women older than 40 years (RR = 3.0, 95% CI [1.1-8.3], p = 0.03) and during first/second trimesters compared to third trimester (RR = 4.0, 95% CI [1.4-12.0], p = 0.01). Crude vaccination coverage was 39% (95% CI, 31-47) and weighted vaccination coverage was estimated at 26% (95% CI, 20-34). Health care provider recommendation for vaccination (corrected OR = 7.8; 95% CI [3.0-17.1]) and non-smoking status (cOR = 2.1; 95% CI [1.2-6.9]) were associated with higher vaccine uptake. This original web based longitudinal surveillance study design proved feasible in pregnant women population. First results are of interest and underline that public health policies should emphasize the vaccination promotion through health care providers. Copyright © 2016 Elsevier Ltd. All rights reserved.

Plant-based anti-HIV-1 strategies: vaccine molecules and antiviral approaches.

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Scotti, Nunzia; Buonaguro, Luigi; Tornesello, Maria Lina; Cardi, Teodoro; Buonaguro, Franco Maria

2010-08-01

The introduction of highly active antiretroviral therapy has drastically changed HIV infection from an acute, very deadly, to a chronic, long-lasting, mild disease. However, this requires continuous care management, which is difficult to implement worldwide, especially in developing countries. Sky-rocketing costs of HIV-positive subjects and the limited success of preventive recommendations mean that a vaccine is urgently needed, which could be the only effective strategy for the real control of the AIDS pandemic. To be effective, vaccination will need to be accessible, affordable and directed against multiple antigens. Plant-based vaccines, which are easy to produce and administer, and require no cold chain for their heat stability are, in principle, suited to such a strategy. More recently, it has been shown that even highly immunogenic, enveloped plant-based vaccines can be produced at a competitive and more efficient rate than conventional strategies. The high variability of HIV epitopes and the need to stimulate both humoral neutralizing antibodies and cellular immunity suggest the importance of using the plant system: it offers a wide range of possible strategies, from single-epitope to multicomponent vaccines, modulators of the immune response (adjuvants) and preventive molecules (microbicides), either alone or in association with plant-derived monoclonal antibodies, besides the potential use of the latter as therapeutic agents. Furthermore, plant-based anti-HIV strategies can be administered not only parenterally but also by the more convenient and safer oral route, which is a more suitable approach for possible mass vaccination.

Immunogenicity of a DNA-launched replicon-based canine parvovirus DNA vaccine expressing VP2 antigen in dogs.

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Dahiya, Shyam S; Saini, Mohini; Kumar, Pankaj; Gupta, Praveen K

2012-10-01

A replicon-based DNA vaccine encoding VP2 gene of canine parvovirus (CPV) was developed by cloning CPV-VP2 gene into a replicon-based DNA vaccine vector (pAlpha). The characteristics of a replicon-based DNA vaccine like, self-amplification of transcripts and induction of apoptosis were analyzed in transfected mammalian cells. When the pAlpha-CPV-VP2 was injected intradermal as DNA-launched replicon-based DNA vaccine in dogs, it induced CPV-specific humoral and cell mediated immune responses. The virus neutralization antibody and lymphocyte proliferative responses were higher than conventional CPV DNA vaccine and commercial CPV vaccine. These results indicated that DNA-launched replicon-based CPV DNA vaccine was effective in inducing both CPV-specific humoral and cellular immune responses and can be considered as effective alternative to conventional CPV DNA vaccine and commercial CPV vaccine. Crown Copyright © 2012. Published by Elsevier India Pvt Ltd. All rights reserved.

Rotavirus vaccines

Directory of Open Access Journals (Sweden)

Kang G

2006-01-01

Full Text Available Rotavirus, the most common cause of severe diarrhea and a leading cause of mortality in children, has been a priority target for vaccine development for the past several years. The first rotavirus vaccine licensed in the United States was withdrawn because of an association of the vaccine with intussusception. However, the need for a vaccine is greatest in the developing world, because the benefits of preventing deaths due to rotavirus disease are substantially greater than the risk of intussusception. Early vaccines were based on animal strains. More recently developed and licenced vaccines are either animal-human reassortants or are based on human strains. In India, two candidate vaccines are in the development process, but have not yet reached efficacy trials. Many challenges regarding vaccine efficacy and safety remain. In addition to completing clinical evaluations of vaccines in development in settings with the highest disease burden and virus diversity, there is also a need to consider alternative vaccine development strategies.

Investigating Stakeholder Attitudes and Opinions on School-Based Human Papillomavirus Vaccination Programs

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Nodulman, Jessica A.; Starling, Randall; Kong, Alberta S.; Buller, David B.; Wheeler, Cosette M.; Woodall, W. Gill

2015-01-01

Background: In several countries worldwide, school-based human papillomavirus (HPV) vaccination programs have been successful; however, little research has explored US stakeholders' acceptance toward school-based HPV vaccination programs. Methods: A total of 13 focus groups and 12 key informant interviews (N?=?117; 85% females; 66% racial/ethnic…

Impact of a website based educational program for increasing vaccination coverage among adolescents.

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Esposito, Susanna; Bianchini, Sonia; Tagliabue, Claudia; Umbrello, Giulia; Madini, Barbara; Di Pietro, Giada; Principi, Nicola

2018-04-03

Data regarding the use of technology to improve adolescent knowledge on vaccines are scarce. The main aim of this study was to evaluate whether different web-based educational programmes for adolescents might increase their vaccination coverage. Overall, 917 unvaccinated adolescents (389 males, 42.4%; mean age ± standard deviation, 14.0 ± 2.2 years) were randomized 1:1:1 into the following groups: no intervention (n = 334), website educational program only (n = 281), or website plus face to face lesson (n = 302) groups. The use of the website plus the lesson significantly increased the overall knowledge of various aspects of vaccine-preventable disease and reduced the fear of vaccines (p education of adolescents while considering all of the vaccines recommended for this age group. Our results demonstrate the possibility of increasing vaccination coverage by using a website based educational program with tailored information. However, to be most effective, this program should be supplemented with face-to-face discussions of vaccines at school and at home. Thus, specific education should also include teachers and parents so that they will be prepared to discuss with adolescents what is true and false in the vaccination field.

Evaluation of peptide selection approaches for epitope‐based vaccine design

DEFF Research Database (Denmark)

Schubert, B.; Lund, Ole; Nielsen, Morten

2013-01-01

A major challenge in epitope-based vaccine (EV) design stems from the vast genomic variation of pathogens and the diversity of the host cellular immune system. Several computational approaches have been published to assist the selection of potential T cell epitopes for EV design. So far, no thoro......A major challenge in epitope-based vaccine (EV) design stems from the vast genomic variation of pathogens and the diversity of the host cellular immune system. Several computational approaches have been published to assist the selection of potential T cell epitopes for EV design. So far...... in terms of in silico measurements simulating important vaccine properties like the ability of inducing protection against a multivariant pathogen in a population; the predicted immunogenicity; pathogen, allele, and population coverage; as well as the conservation of selected epitopes. Additionally, we...... evaluate the use of human leukocyte antigen (HLA) supertypes with regards to their applicability for population-spanning vaccine design. The results showed that in terms of induced protection methods that simultaneously aim to optimize pathogen and HLA coverage significantly outperform methods focusing...

Immunotherapy for Alzheimer's disease: DNA- and protein-based epitope vaccines.

Science.gov (United States)

Davtyan, Hayk; Petrushina, Irina; Ghochikyan, Anahit

2014-01-01

Active immunotherapy for Alzheimer's disease (AD) is aimed to induce antibodies specific to amyloid-beta (Aβ) that are capable to reduce the level of Aβ in the CNS of Alzheimer's disease patients. First clinical trial AN-1792 that was based on vaccination with full-length Aβ42 showed that safe and effective AD vaccine should induce high titers of anti-Aβ antibodies without activation of harmful autoreactive T cells. Replacement of self-T cell epitope with foreign epitope, keeping self-B cell epitope intact, may allow to induce high titers of anti-Aβ antibodies while avoiding the activation of T cells specific to Aβ. Here we describe the protocols for evaluation of AD DNA- or multiple antigenic peptide (MAP)-based epitope vaccines composed of Aβ(1-11) B cell epitope fused to synthetic T cell epitope PADRE (Aβ(1-11)-PADRE). All protocols could be used for testing any epitope vaccine constructed in your lab and composed of other T cell epitopes using the appropriate peptides in tests for evaluation of humoral and cellular immune responses.

Can dendritic cells improve whole cancer cell vaccines based on immunogenically killed cancer cells?

Science.gov (United States)

Cicchelero, Laetitia; Denies, Sofie; Devriendt, Bert; de Rooster, Hilde; Sanders, Niek N

2015-01-01

Immunogenic cell death (ICD) offers interesting opportunities in cancer cell (CC) vaccine manufacture, as it increases the immunogenicity of the dead CC. Furthermore, fusion of CCs with dendritic cells (DCs) is considered a superior method for generating whole CC vaccines. Therefore, in this work, we determined in naive mice whether immunogenically killed CCs per se (CC vaccine) elicit an antitumoral immune response different from the response observed when immunogenically killed CCs are associated with DCs through fusion (fusion vaccine) or through co-incubation (co-incubation vaccine). After tumor inoculation, the type of immune response in the prophylactically vaccinated mice differed between the groups. In more detail, fusion vaccines elicited a humoral anticancer response, whereas the co-incubation and CC vaccine mainly induced a cellular response. Despite these differences, all three approaches offered a prophylactic protection against tumor development in the murine mammary carcinoma model. In summary, it can be concluded that whole CC vaccines based on immunogenically killed CCs may not necessarily require association with DCs to elicit a protective anticancer immune response. If this finding can be endorsed in other cancer models, the manufacture of CC vaccines would greatly benefit from this new insight, as production of DC-based vaccines is laborious, time-consuming and expensive. PMID:26587315

Novel Vaccine Against Mycoplasma Hyosynoviae: The Immunogenic Effect of Iscom-Based Vaccines in Swine

DEFF Research Database (Denmark)

Lauritsen, Klara Tølbøll; Vinther Heydenreich, Annette; Riber, Ulla

Arthritis in swine is frequently caused by Mycoplasma hyosynoviae (Mhs). For the development of an effective vaccine we investigated the immunogenic effect of three vaccine preparations with the ISCOM adjuvant Posintro™ from Nordic Vaccine. A: formalin fixed whole-cells Mhs (300 µg/dose) mixed...... with Posintro, B: Deoxycholate extracted lipoproteins from Mhs organisms (DOC-antigen, 300 μg/dose) in Posintro and C: DOC-antigen (50 μg/dose) in Posintro. Each vaccine-group contained three pigs. Vaccinations (i.m.) were performed at 12 and 15 weeks of age. The development of specific IgG and secretion...... of IFNγ were measured. Three weeks after the second vaccination, pigs were euthanised and autopsied. Vaccine B induced a high level of specific serum IgG in all pigs a week after boost. Vaccine C gave a variable response after boost, with two pigs seroconverting, while no response was seen by vaccine A...

School-Based Influenza Vaccination: Health and Economic Impact of Maine's 2009 Influenza Vaccination Program.

Science.gov (United States)

Basurto-Dávila, Ricardo; Meltzer, Martin I; Mills, Dora A; Beeler Asay, Garrett R; Cho, Bo-Hyun; Graitcer, Samuel B; Dube, Nancy L; Thompson, Mark G; Patel, Suchita A; Peasah, Samuel K; Ferdinands, Jill M; Gargiullo, Paul; Messonnier, Mark; Shay, David K

2017-12-01

To estimate the societal economic and health impacts of Maine's school-based influenza vaccination (SIV) program during the 2009 A(H1N1) influenza pandemic. Primary and secondary data covering the 2008-09 and 2009-10 influenza seasons. We estimated weekly monovalent influenza vaccine uptake in Maine and 15 other states, using difference-in-difference-in-differences analysis to assess the program's impact on immunization among six age groups. We also developed a health and economic Markov microsimulation model and conducted Monte Carlo sensitivity analysis. We used national survey data to estimate the impact of the SIV program on vaccine coverage. We used primary data and published studies to develop the microsimulation model. The program was associated with higher immunization among children and lower immunization among adults aged 18-49 years and 65 and older. The program prevented 4,600 influenza infections and generated $4.9 million in net economic benefits. Cost savings from lower adult vaccination accounted for 54 percent of the economic gain. Economic benefits were positive in 98 percent of Monte Carlo simulations. SIV may be a cost-beneficial approach to increase immunization during pandemics, but programs should be designed to prevent lower immunization among nontargeted groups. © Health Research and Educational Trust.

Making evidence-based selections of influenza vaccines.

Science.gov (United States)

Childress, Billy-Clyde; Montney, Joshua D; Albro, Elise A

2014-01-01

Years ago, intramuscular influenza vaccines were the only option for those who wanted to arm themselves against the flu. Today there are alternatives, including intradermal injections and intranasal sprays. In order to select the right influenza vaccine for their patients, pharmacists, and other healthcare professionals must have a basic understanding of the immune system. Influenza vaccines elicit different levels of immune response involving innate and adaptive immunity, which are critical to fighting infection. For the 2013-2014 flu season, there were 13 different formulations of influenza vaccines on the market with vast differences in indications, contraindications, and effectiveness. The CDC does not recommend one vaccine over another, but recommends that all patients be vaccinated against the flu. Preventing the spread of influenza is no simple task; however, the most recent evidence on influenza vaccines and sufficient knowledge of the immune system will allow pharmacists and other healthcare providers to better advocate for vaccines, determine which are most appropriate, and ensure their proper administration.

Ontology-based literature mining of E. coli vaccine-associated gene interaction networks.

Science.gov (United States)

Hur, Junguk; Özgür, Arzucan; He, Yongqun

2017-03-14

Pathogenic Escherichia coli infections cause various diseases in humans and many animal species. However, with extensive E. coli vaccine research, we are still unable to fully protect ourselves against E. coli infections. To more rational development of effective and safe E. coli vaccine, it is important to better understand E. coli vaccine-associated gene interaction networks. In this study, we first extended the Vaccine Ontology (VO) to semantically represent various E. coli vaccines and genes used in the vaccine development. We also normalized E. coli gene names compiled from the annotations of various E. coli strains using a pan-genome-based annotation strategy. The Interaction Network Ontology (INO) includes a hierarchy of various interaction-related keywords useful for literature mining. Using VO, INO, and normalized E. coli gene names, we applied an ontology-based SciMiner literature mining strategy to mine all PubMed abstracts and retrieve E. coli vaccine-associated E. coli gene interactions. Four centrality metrics (i.e., degree, eigenvector, closeness, and betweenness) were calculated for identifying highly ranked genes and interaction types. Using vaccine-related PubMed abstracts, our study identified 11,350 sentences that contain 88 unique INO interactions types and 1,781 unique E. coli genes. Each sentence contained at least one interaction type and two unique E. coli genes. An E. coli gene interaction network of genes and INO interaction types was created. From this big network, a sub-network consisting of 5 E. coli vaccine genes, including carA, carB, fimH, fepA, and vat, and 62 other E. coli genes, and 25 INO interaction types was identified. While many interaction types represent direct interactions between two indicated genes, our study has also shown that many of these retrieved interaction types are indirect in that the two genes participated in the specified interaction process in a required but indirect process. Our centrality analysis of

Enhanced cellular immune response against SIV Gag induced by immunization with DNA vaccines expressing assembly and release-defective SIV Gag proteins

International Nuclear Information System (INIS)

Bu Zhigao; Ye Ling; Compans, Richard W.; Yang Chinglai

2003-01-01

Codon-optimized genes were synthesized for the SIVmac239 Gag, a mutant Gag with mutations in the major homology region, and a chimeric Gag containing a protein destruction signal at the N-terminus of Gag. The mutant and chimeric Gag were expressed at levels comparable to that observed for the wild-type Gag protein but their stability and release into the medium were found to be significantly reduced. Immunization of mice with DNA vectors encoding the mutant or chimeric Gag induced fourfold higher levels of anti-SIV Gag CD4 T cell responses than the DNA vector encoding the wild-type SIV Gag. Moreover, anti-SIV Gag CD8 T cell responses induced by DNA vectors encoding the mutant or chimeric Gag were found to be 5- to 10-fold higher than those induced by the DNA construct for the wild-type Gag. These results indicate that mutations disrupting assembly and/or stability of the SIV Gag protein effectively enhance its immunogenicity when expressed from DNA vaccines

School-based human papillomavirus vaccination: An opportunity to ...

African Journals Online (AJOL)

School-based human papillomavirus vaccination: An opportunity to increase knowledge about cervical cancer and improve uptake of ... Poor knowledge about cervical cancer plays a role in limiting screening uptake. HPV ... Article Metrics.

Bacterial superglue enables easy development of efficient virus-like particle based vaccines

DEFF Research Database (Denmark)

Thrane, Susan; Janitzek, Christoph M; Matondo, Sungwa

2016-01-01

BACKGROUND: Virus-like particles (VLPs) represent a significant advance in the development of subunit vaccines, combining high safety and efficacy. Their particulate nature and dense repetitive subunit organization makes them ideal scaffolds for display of vaccine antigens. Traditional approaches...... for VLP-based antigen display require labor-intensive trial-and-error optimization, and often fail to generate dense antigen display. Here we utilize the split-intein (SpyTag/SpyCatcher) conjugation system to generate stable isopeptide bound antigen-VLP complexes by simply mixing of the antigen and VLP......). CONCLUSIONS: The spy-VLP system constitutes a versatile and rapid method to develop highly immunogenic VLP-based vaccines. Our data provide proof-of-concept for the technology's ability to present complex vaccine antigens to the immune system and elicit robust functional antibody responses as well...

Effect of HIV-1 envelope cytoplasmic tail on adenovirus primed virus encoded virus-like particle immunizations

DEFF Research Database (Denmark)

Andersson, Anne Marie C; Ragonnaud, Emeline; Seaton, Kelly E.

2016-01-01

were found between the different priming regimens as both induced high titered tier 1 neutralizing antibodies, but no tier 2 antibodies, possibly reflecting the similar presentation of trimer specific antibody epitopes. The described vaccine regimens provide insight into the effects of the HIV-1 Env......The low number of envelope (Env) spikes presented on native HIV-1 particles is a major impediment for HIV-1 prophylactic vaccine development. We designed virus-like particle encoding adenoviral vectors utilizing SIVmac239 Gag as an anchor for full length and truncated HIV-1 M consensus Env...

Side-by-side comparison of gene-based smallpox vaccine with MVA in nonhuman primates.

Science.gov (United States)

Golden, Joseph W; Josleyn, Matthew; Mucker, Eric M; Hung, Chien-Fu; Loudon, Peter T; Wu, T C; Hooper, Jay W

2012-01-01

Orthopoxviruses remain a threat as biological weapons and zoonoses. The licensed live-virus vaccine is associated with serious health risks, making its general usage unacceptable. Attenuated vaccines are being developed as alternatives, the most advanced of which is modified-vaccinia virus Ankara (MVA). We previously developed a gene-based vaccine, termed 4pox, which targets four orthopoxvirus antigens, A33, B5, A27 and L1. This vaccine protects mice and non-human primates from lethal orthopoxvirus disease. Here, we investigated the capacity of the molecular adjuvants GM-CSF and Escherichia coli heat-labile enterotoxin (LT) to enhance the efficacy of the 4pox gene-based vaccine. Both adjuvants significantly increased protective antibody responses in mice. We directly compared the 4pox plus LT vaccine against MVA in a monkeypox virus (MPXV) nonhuman primate (NHP) challenge model. NHPs were vaccinated twice with MVA by intramuscular injection or the 4pox/LT vaccine delivered using a disposable gene gun device. As a positive control, one NHP was vaccinated with ACAM2000. NHPs vaccinated with each vaccine developed anti-orthopoxvirus antibody responses, including those against the 4pox antigens. After MPXV intravenous challenge, all control NHPs developed severe disease, while the ACAM2000 vaccinated animal was well protected. All NHPs vaccinated with MVA were protected from lethality, but three of five developed severe disease and all animals shed virus. All five NHPs vaccinated with 4pox/LT survived and only one developed severe disease. None of the 4pox/LT-vaccinated animals shed virus. Our findings show, for the first time, that a subunit orthopoxvirus vaccine delivered by the same schedule can provide a degree of protection at least as high as that of MVA.

Side-by-side comparison of gene-based smallpox vaccine with MVA in nonhuman primates.

Directory of Open Access Journals (Sweden)

Joseph W Golden

Full Text Available Orthopoxviruses remain a threat as biological weapons and zoonoses. The licensed live-virus vaccine is associated with serious health risks, making its general usage unacceptable. Attenuated vaccines are being developed as alternatives, the most advanced of which is modified-vaccinia virus Ankara (MVA. We previously developed a gene-based vaccine, termed 4pox, which targets four orthopoxvirus antigens, A33, B5, A27 and L1. This vaccine protects mice and non-human primates from lethal orthopoxvirus disease. Here, we investigated the capacity of the molecular adjuvants GM-CSF and Escherichia coli heat-labile enterotoxin (LT to enhance the efficacy of the 4pox gene-based vaccine. Both adjuvants significantly increased protective antibody responses in mice. We directly compared the 4pox plus LT vaccine against MVA in a monkeypox virus (MPXV nonhuman primate (NHP challenge model. NHPs were vaccinated twice with MVA by intramuscular injection or the 4pox/LT vaccine delivered using a disposable gene gun device. As a positive control, one NHP was vaccinated with ACAM2000. NHPs vaccinated with each vaccine developed anti-orthopoxvirus antibody responses, including those against the 4pox antigens. After MPXV intravenous challenge, all control NHPs developed severe disease, while the ACAM2000 vaccinated animal was well protected. All NHPs vaccinated with MVA were protected from lethality, but three of five developed severe disease and all animals shed virus. All five NHPs vaccinated with 4pox/LT survived and only one developed severe disease. None of the 4pox/LT-vaccinated animals shed virus. Our findings show, for the first time, that a subunit orthopoxvirus vaccine delivered by the same schedule can provide a degree of protection at least as high as that of MVA.

Pre-Vaccination Care-Seeking in Females Reporting Severe Adverse Reactions to HPV Vaccine. A Registry Based Case-Control Study.

Directory of Open Access Journals (Sweden)

Kåre Mølbak

Full Text Available Since 2013 the number of suspected adverse reactions to the quadrivalent human papillomavirus (HPV vaccine reported to the Danish Medicines Agency (DMA has increased. Due to the resulting public concerns about vaccine safety, the coverage of HPV vaccinations in the childhood vaccination programme has declined. The aim of the present study was to determine health care-seeking prior to the first HPV vaccination among females who suspected adverse reactions to HPV vaccine.In this registry-based case-control study, we included as cases vaccinated females with reports to the DMA of suspected severe adverse reactions. We selected controls without reports of adverse reactions from the Danish vaccination registry and matched by year of vaccination, age of vaccination, and municipality, and obtained from the Danish National Patient Registry and The National Health Insurance Service Register the history of health care usage two years prior to the first vaccine. We analysed the data by logistic regression while adjusting for the matching variables.The study included 316 cases who received first HPV vaccine between 2006 and 2014. Age range of cases was 11 to 52 years, with a peak at 12 years, corresponding to the recommended age at vaccination, and another peak at 19 to 28 years, corresponding to a catch-up programme targeting young women. Compared with 163,910 controls, cases had increased care-seeking in the two years before receiving the first HPV vaccine. A multivariable model showed higher use of telephone/email consultations (OR 1.9; 95% CI 1.2-3.2, physiotherapy (OR 2.1; 95% CI 1.6-2.8 and psychologist/psychiatrist (OR 1.9; 95% CI 1.3-2.7. Cases were more likely to have a diagnosis in the ICD-10 chapters of diseases of the digestive system (OR 1.6; 95% CI 1.0-2.4, of the musculoskeletal system (OR 1.6; 95% CI 1.1-2.2, symptoms or signs not classified elsewhere (OR 1.8; 95% CI 1.3-2.5 as well as injuries (OR 1.5; 95% CI 1.2-1.9.Before receiving the

Ethical and legal challenges of vaccines and vaccination: Reflections.

Science.gov (United States)

Jesani, Amar; Johari, Veena

2017-01-01

Vaccines and vaccination have emerged as key medical scientific tools for prevention of certain diseases. Documentation of the history of vaccination shows that the initial popular resistance to universal vaccination was based on false assumptions and eventually gave way to acceptance of vaccines and trust in their ability to save lives. The successes of the global eradication of smallpox, and now of polio, have only strengthened the premier position occupied by vaccines in disease prevention. However, the success of vaccines and public trust in their ability to eradicate disease are now under challenge, as increasing numbers of people refuse vaccination, questioning the effectiveness of vaccines and the need to vaccinate.

Egg-Independent Influenza Vaccines and Vaccine Candidates

Directory of Open Access Journals (Sweden)

Ilaria Manini

2017-07-01

Full Text Available Vaccination remains the principal way to control seasonal infections and is the most effective method of reducing influenza-associated morbidity and mortality. Since the 1940s, the main method of producing influenza vaccines has been an egg-based production process. However, in the event of a pandemic, this method has a significant limitation, as the time lag from strain isolation to final dose formulation and validation is six months. Indeed, production in eggs is a relatively slow process and production yields are both unpredictable and highly variable from strain to strain. In particular, if the next influenza pandemic were to arise from an avian influenza virus, and thus reduce the egg-laying hen population, there would be a shortage of embryonated eggs available for vaccine manufacturing. Although the production of egg-derived vaccines will continue, new technological developments have generated a cell-culture-based influenza vaccine and other more recent platforms, such as synthetic influenza vaccines.

Immune complex-based vaccine for pig protection against parvovirus.

Science.gov (United States)

Roić, B; Cajavec, S; Ergotić, N; Lipej, Z; Madić, J; Lojkić, M; Pokrić, B

2006-02-01

generated by the IC containing the allogeneic antibodies were higher than that generated by the ICs containing the xenogeneic pig antibodies. It was similar to that generated by two-times higher content of the virus material administered by a commercially available vaccine. The IC-based vaccines belong to non-replicating, subunit vaccines, which are both ecologically convenient and the safest vaccines of all.

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

Science.gov (United States)

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.

Overcoming the knowledge-behavior gap: The effect of evidence-based HPV vaccination leaflets on understanding, intention, and actual vaccination decision.

Science.gov (United States)

Wegwarth, O; Kurzenhäuser-Carstens, S; Gigerenzer, G

2014-03-10

Informed decision making requires transparent and evidence-based (=balanced) information on the potential benefit and harms of medical preventions. An analysis of German HPV vaccination leaflets revealed, however, that none met the standards of balanced risk communication. We surveyed a sample of 225 girl-parent pairs in a before-after design on the effects of balanced and unbalanced risk communication on participants' knowledge about cervical cancer and the HPV vaccination, their perceived risk, their intention to have the vaccine, and their actual vaccination decision. The balanced leaflet increased the number of participants who were correctly informed about cervical cancer and the HPV vaccine by 33 to 66 absolute percentage points. In contrast, the unbalanced leaflet decreased the number of participants who were correctly informed about these facts by 0 to 18 absolute percentage points. Whereas the actual uptake of the HPV vaccination 14 months after the initial study did not differ between the two groups (22% balanced leaflet vs. 23% unbalanced leaflet; p=.93, r=.01), the originally stated intention to have the vaccine reliably predicted the actual vaccination decision for the balanced leaflet group only (concordance between intention and actual uptake: 97% in the balanced leaflet group, rs=.92, p=.00; 60% in the unbalanced leaflet group, rs=.37, p=.08). In contrast to a unbalanced leaflet, a balanced leaflet increased people's knowledge of the HPV vaccination, improved perceived risk judgments, and led to an actual vaccination uptake, which first was robustly predicted by people's intention and second did not differ from the uptake in the unbalanced leaflet group. These findings suggest that balanced reporting about HPV vaccination increases informed decisions about whether to be vaccinated and does not undermine actual uptake. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Comparison of Current Regulatory Status for Gene-Based Vaccines in the U.S., Europe and Japan

Directory of Open Access Journals (Sweden)

Yoshikazu Nakayama

2015-03-01

Full Text Available Gene-based vaccines as typified by plasmid DNA vaccines and recombinant viral-vectored vaccines are expected as promising solutions against infectious diseases for which no effective prophylactic vaccines exist such as HIV, dengue virus, Ebola virus and malaria, and for which more improved vaccines are needed such as tuberculosis and influenza virus. Although many preclinical and clinical trials have been conducted to date, no DNA vaccines or recombinant viral-vectored vaccines expressing heterologous antigens for human use have yet been licensed in the U.S., Europe or Japan. In this research, we describe the current regulatory context for gene-based prophylactic vaccines against infectious disease in the U.S., Europe, and Japan. We identify the important considerations, in particular, on the preclinical assessments that would allow these vaccines to proceed to clinical trials, and the differences on the regulatory pathway for the marketing authorization in each region.

Are Clade Specific HIV Vaccines a Necessity? An Analysis Based on Mathematical Models

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Dobromir Dimitrov

2015-12-01

Full Text Available As HIV-1 envelope immune responses are critical to vaccine related protection, most candidate HIV vaccines entering efficacy trials are based upon a clade specific design. This need for clade specific vaccine prototypes markedly reduces the implementation of potentially effective HIV vaccines. We utilized a mathematical model to determine the effectiveness of immediate roll-out of a non-clade matched vaccine with reduced efficacy compared to constructing clade specific vaccines, which would take considerable time to manufacture and test in safety and efficacy trials. We simulated the HIV epidemic in San Francisco (SF and South Africa (SA and projected effectiveness of three vaccination strategies: i immediate intervention with a 20–40% vaccine efficacy (VE non-matched vaccine, ii delayed intervention by developing a 50% VE clade-specific vaccine, and iii immediate intervention with a non-matched vaccine replaced by a clade-specific vaccine when developed. Immediate vaccination with a non-clade matched vaccine, even with reduced efficacy, would prevent thousands of new infections in SF and millions in SA over 30 years. Vaccination with 50% VE delayed for five years needs six and 12 years in SA to break-even with immediate 20 and 30% VE vaccination, respectively, while not able to surpass the impact of immediate 40% VE vaccination over 30 years. Replacing a 30% VE with a 50% VE vaccine after 5 years reduces the HIV acquisition by 5% compared to delayed vaccination. The immediate use of an HIV vaccine with reduced VE in high risk communities appears desirable over a short time line but higher VE should be the pursued to achieve strong long-term impact. Our analysis illustrates the importance of developing surrogate markers (correlates of protection to allow bridging types of immunogenicity studies to support more rapid assessment of clade specific vaccines.

Live virus vaccines based on a yellow fever vaccine backbone: standardized template with key considerations for a risk/benefit assessment.

Science.gov (United States)

Monath, Thomas P; Seligman, Stephen J; Robertson, James S; Guy, Bruno; Hayes, Edward B; Condit, Richard C; Excler, Jean Louis; Mac, Lisa Marie; Carbery, Baevin; Chen, Robert T

2015-01-01

The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) was formed to evaluate the safety of live, recombinant viral vaccines incorporating genes from heterologous viruses inserted into the backbone of another virus (so-called "chimeric virus vaccines"). Many viral vector vaccines are in advanced clinical trials. The first such vaccine to be approved for marketing (to date in Australia, Thailand, Malaysia, and the Philippines) is a vaccine against the flavivirus, Japanese encephalitis (JE), which employs a licensed vaccine (yellow fever 17D) as a vector. In this vaccine, two envelope proteins (prM-E) of YF 17D virus were exchanged for the corresponding genes of JE virus, with additional attenuating mutations incorporated into the JE gene inserts. Similar vaccines have been constructed by inserting prM-E genes of dengue and West Nile into YF 17D virus and are in late stage clinical studies. The dengue vaccine is, however, more complex in that it requires a mixture of four live vectors each expressing one of the four dengue serotypes. This vaccine has been evaluated in multiple clinical trials. No significant safety concerns have been found. The Phase 3 trials met their endpoints in terms of overall reduction of confirmed dengue fever, and, most importantly a significant reduction in severe dengue and hospitalization due to dengue. However, based on results that have been published so far, efficacy in preventing serotype 2 infection is less than that for the other three serotypes. In the development of these chimeric vaccines, an important series of comparative studies of safety and efficacy were made using the parental YF 17D vaccine virus as a benchmark. In this paper, we use a standardized template describing the key characteristics of the novel flavivirus vaccine vectors, in comparison to the parental YF 17D vaccine. The template facilitates scientific discourse among key stakeholders by increasing the transparency and comparability of

Zika virus-like particle (VLP) based vaccine

Science.gov (United States)

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

Parents' decision-making regarding vaccinating their children against influenza: A web-based survey.

Science.gov (United States)

Flood, Emuella M; Rousculp, Matthew D; Ryan, Kellie J; Beusterien, Kathleen M; Divino, Victoria M; Toback, Seth L; Sasané, Medha; Block, Stan L; Hall, Matthew C; Mahadevia, Parthiv J

2010-08-01

Despite the recommendation from the Centers for Disease Control and Prevention that children between the ages of 6 months and 18 years be vaccinated against influenza annually, vaccination rates remain suboptimal. This study was conducted to explore factors that influence parents' decisions regarding influenza vaccination for children aged 2 to 12 years, to quantify the relative importance of these factors, to identify an appropriate theoretical model for illustrating the relationships among these factors, and to characterize parents by their likelihood of vaccinating their children against influenza. A quantitative Web-based survey was administered to a sample of parents from an online panel representative of the US population. Parents were stratified based on self-reported rates of their personal influenza vaccination (every year, sometimes, or never) and the age of their child (2-4 years or 5-12 years). The results were examined by parents' likelihood of vaccinating their child in the next year (high, medium, or low). Participants were asked to rank their agreement with statements representing various beliefs and perceptions about influenza and influenza vaccine on a scale from 1 = strongly agree to 5 = strongly disagree. Parents who indicated that they vaccinate their child every year were asked to select the drivers of their decision to vaccinate; parents who indicated that they never vaccinate their child were asked to select the barriers affecting their decision not to vaccinate; and parents who responded that they sometimes vaccinate their child were asked to select both the drivers and barriers affecting their decision. Participants were then asked to rank the importance of each driver or barrier on a scale from 1 = a little important to 5 = extremely important. Mean agreement ratings were calculated for parents' beliefs and perceptions about influenza and influenza vaccine and were compared across likelihood subgroups. Mean importance ratings of the

Immunological consequences of using three different clinical/laboratory techniques of emulsifying peptide-based vaccines in incomplete Freund's adjuvant

Directory of Open Access Journals (Sweden)

Kast W Martin

2006-10-01

Full Text Available Abstract Incomplete Freund's adjuvant (IFA serves as a carrier for water-in-oil emulsion (W/O vaccines. The stability of such emulsions greatly affects vaccine safety and efficacy since continued presence of antigen depots at lymphoid organs releasing low-level antigens is known to stimulate a potent immune response and high-level systemic release of antigens can lead to tolerance. W/O emulsions for the purpose of clinical and laboratory peptide-based vaccinations have been prepared using the techniques of syringe extrusion, vortex or high-speed homogenization. There is no consensus in the field over which technique would be best to use and no immunological data are available that compare the three techniques. In this study, we compared the immune responses induced by a peptide-based vaccine prepared using vortex, syringe-extrusion and homogenization. The vaccination led to tumor rejection by mice vaccinated with the peptide-based vaccine prepared using all three techniques. The immunological data from the in vivo cytotoxicity assay showed a trend for lower responses and a higher variability and greater range in the immune responses induced by a vaccine that was emulsified by the vortex or homogenizer techniques as compared to the syringe-extrusion technique. There were statistically significant lower numbers of IFNγ-secreting cells induced when the mice were vaccinated with a peptide-based vaccine emulsion prepared using the vortex compared to the syringe-extrusion technique. At a suboptimal vaccine dose, the mice vaccinated with a peptide-based vaccine emulsion prepared using the vortex technique had the largest tumors compared to the syringe-extrusion or the homogenizer technique. In the setting of a busy pharmacy that prepares peptide-based vaccine emulsions for clinical studies, the vortex technique can still be used but we urge investigators to take special care in their choice of mixing vessels for the vortex technique as that can

Synthetic biology devices and circuits for RNA-based 'smart vaccines': a propositional review.

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Andries, Oliwia; Kitada, Tasuku; Bodner, Katie; Sanders, Niek N; Weiss, Ron

2015-02-01

Nucleic acid vaccines have been gaining attention as an alternative to the standard attenuated pathogen or protein based vaccine. However, an unrealized advantage of using such DNA or RNA based vaccination modalities is the ability to program within these nucleic acids regulatory devices that would provide an immunologist with the power to control the production of antigens and adjuvants in a desirable manner by administering small molecule drugs as chemical triggers. Advances in synthetic biology have resulted in the creation of highly predictable and modular genetic parts and devices that can be composed into synthetic gene circuits with complex behaviors. With the recent advent of modified RNA gene delivery methods and developments in the RNA replicon platform, we foresee a future in which mammalian synthetic biologists will create genetic circuits encoded exclusively on RNA. Here, we review the current repertoire of devices used in RNA synthetic biology and propose how programmable 'smart vaccines' will revolutionize the field of RNA vaccination.

Implementation of a national school-based Human Papillomavirus (HPV) vaccine campaign in Fiji: knowledge, vaccine acceptability and information needs of parents.

Science.gov (United States)

La Vincente, S F; Mielnik, D; Jenkins, K; Bingwor, F; Volavola, L; Marshall, H; Druavesi, P; Russell, F M; Lokuge, K; Mulholland, E K

2015-12-18

In 2008 Fiji implemented a nationwide Human Papillomavirus (HPV) vaccine campaign targeting all girls aged 9-12 years through the existing school-based immunisation program. Parents of vaccine-eligible girls were asked to provide written consent for vaccination. The purpose of this study was to describe parents' knowledge, experiences and satisfaction with the campaign, the extent to which information needs for vaccine decision-making were met, and what factors were associated with vaccine consent. Following vaccine introduction, a cross-sectional telephone survey was conducted with parents of vaccine-eligible girls from randomly selected schools, stratified by educational district. Factors related to vaccine consent were explored using Generalised Estimating Equations. There were 560 vaccine-eligible girls attending the participating 19 schools at the time of the campaign. Among these, 313 parents could be contacted, with 293 agreeing to participate (93.6%). Almost 80% of participants reported having consented to HPV vaccination (230/293, 78.5%). Reported knowledge of cervical cancer and HPV prior to the campaign was very low. Most respondents reported that they were satisfied with their access to information to make an informed decision about HPV vaccination (196/293, 66.9%). and this was very strongly associated with provision of consent. Despite their young age, the vaccine-eligible girls were often involved in the discussion and decision-making. Most consenting parents were satisfied with the campaign and their decision to vaccinate, with almost 90% indicating they would consent to future HPV vaccination. However, negative media reports about the vaccine campaign created confusion and concern. Local health staff were cited as a trusted source of information to guide decision-making. Just over half of the participants who withheld consent cited vaccine safety fears as the primary reason (23/44, 52.3%). This is the first reported experience of HPV introduction

Bioinformatics analysis of Brucella vaccines and vaccine targets using VIOLIN.

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He, Yongqun; Xiang, Zuoshuang

2010-09-27

Brucella spp. are Gram-negative, facultative intracellular bacteria that cause brucellosis, one of the commonest zoonotic diseases found worldwide in humans and a variety of animal species. While several animal vaccines are available, there is no effective and safe vaccine for prevention of brucellosis in humans. VIOLIN (http://www.violinet.org) is a web-based vaccine database and analysis system that curates, stores, and analyzes published data of commercialized vaccines, and vaccines in clinical trials or in research. VIOLIN contains information for 454 vaccines or vaccine candidates for 73 pathogens. VIOLIN also contains many bioinformatics tools for vaccine data analysis, data integration, and vaccine target prediction. To demonstrate the applicability of VIOLIN for vaccine research, VIOLIN was used for bioinformatics analysis of existing Brucella vaccines and prediction of new Brucella vaccine targets. VIOLIN contains many literature mining programs (e.g., Vaxmesh) that provide in-depth analysis of Brucella vaccine literature. As a result of manual literature curation, VIOLIN contains information for 38 Brucella vaccines or vaccine candidates, 14 protective Brucella antigens, and 68 host response studies to Brucella vaccines from 97 peer-reviewed articles. These Brucella vaccines are classified in the Vaccine Ontology (VO) system and used for different ontological applications. The web-based VIOLIN vaccine target prediction program Vaxign was used to predict new Brucella vaccine targets. Vaxign identified 14 outer membrane proteins that are conserved in six virulent strains from B. abortus, B. melitensis, and B. suis that are pathogenic in humans. Of the 14 membrane proteins, two proteins (Omp2b and Omp31-1) are not present in B. ovis, a Brucella species that is not pathogenic in humans. Brucella vaccine data stored in VIOLIN were compared and analyzed using the VIOLIN query system. Bioinformatics curation and ontological representation of Brucella vaccines

Live Virus Vaccines Based on a Yellow Fever Vaccine Backbone: Standardized Template with Key Considerations for a Risk/Benefit Assessment*

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Monath, Thomas P.; Seligman, Stephen J.; Robertson, James S.; Guy, Bruno; Hayes, Edward B.; Condit, Richard C.; Excler, Jean Louis; Mac, Lisa Marie; Carbery, Baevin; Chen, Robert T

2015-01-01

The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) was formed to evaluate the safety of live, recombinant viral vaccines incorporating genes from heterologous viruses inserted into the backbone of another virus (so-called “chimeric virus vaccines”). Many viral vector vaccines are in advanced clinical trials. The first such vaccine to be approved for marketing (to date in Australia, Thailand, Malaysia, and the Philippines) is a vaccine against the flavivirus Japanese encephalitis (JE), which employs a licensed vaccine (yellow fever 17D) as a vector. In this vaccine, two envelope proteins (prM-E) of YF 17D virus were replaced by the corresponding genes of JE virus, with additional attenuating mutations incorporated into the JE gene inserts. Similar vaccines have been constructed by inserting prM-E genes of dengue and West Nile into YF 17D virus and are in late stage clinical studies. The dengue vaccine is, however, more complex in that it requires a mixture of four live vectors each expressing one of the four dengue serotypes. This vaccine has been evaluated in multiple clinical trials. No significant safety concerns have been found. The Phase 3 trials met their endpoints in terms of overall reduction of confirmed dengue fever, and, most importantly a significant reduction in severe dengue and hospitalization due to dengue. However, based on results that have been published so far, efficacy in preventing serotype 2 infection is less than that for the other three serotypes. In the development of these chimeric vaccines, an important series of comparative studies of safety and efficacy were made using the parental YF 17D vaccine virus as a benchmark. In this paper, we use a standardized template describing the key characteristics of the novel flavivirus vaccine vectors, in comparison to the parental YF 17D vaccine. The template facilitates scientific discourse among key stakeholders by increasing the transparency and comparability of

Gene-based vaccine development for improving animal production in developing countries. Possibilities and constraints

International Nuclear Information System (INIS)

Egerton, J.R.

2005-01-01

For vaccine production, recombinant antigens must be protective. Identifying protective antigens or candidate antigens is an essential precursor to vaccine development. Even when a protective antigen has been identified, cloning of its gene does not lead directly to vaccine development. The fimbrial protein of Dichelobacter nodosus, the agent of foot-rot in ruminants, was known to be protective. Recombinant vaccines against this infection are ineffective if expressed protein subunits are not assembled as mature fimbriae. Antigenic competition between different, but closely related, recombinant antigens limited the use of multivalent vaccines based on this technology. Recombinant antigens may need adjuvants to enhance response. DNA vaccines, potentiated with genes for different cytokines, may replace the need for aggressive adjuvants, and especially where cellular immunity is essential for protection. The expression of antigens from animal pathogens in plants and the demonstration of some immunity to a disease like rinderpest after ingestion of these, suggests an alternative approach to vaccination by injection. Research on disease pathogenesis and the identification of candidate antigens is specific to the disease agent. The definition of expression systems and the formulation of a vaccine for each disease must be followed by research to establish safety and efficacy. Where vaccines are based on unique gene sequences, the intellectual property is likely to be protected by patent. Organizations, licensed to produce recombinant vaccines, expect to recover their costs and to make a profit. The consequence is that genetically-derived vaccines are expensive. The capacity of vaccines to help animal owners of poorer countries depends not only on quality and cost but also on the veterinary infrastructure where they are used. Ensuring the existence of an effective animal health infrastructure in developing countries is as great a challenge for the developed world as

Liposome-Based Adjuvants for Subunit Vaccines: Formulation Strategies for Subunit Antigens and Immunostimulators

DEFF Research Database (Denmark)

Schmidt, Signe Tandrup; Foged, Camilla; Korsholm, Karen Smith

2016-01-01

be classified into delivery systems or immunostimulators. Liposomes are versatile delivery systems for antigens, and they can carefully be customized towards desired immune profiles by combining them with immunostimulators and optimizing their composition, physicochemical properties and antigen-loading mode......The development of subunit vaccines has become very attractive in recent years due to their superior safety profiles as compared to traditional vaccines based on live attenuated or whole inactivated pathogens, and there is an unmet medical need for improved vaccines and vaccines against pathogens...... of immunostimulators and antigens, respectively, into liposomes, and the choice of immunostimulator should ideally be based on knowledge regarding the specific PRR expression profile of the target APCs. Here, we review state-of-the-art formulation approaches employed for the inclusion of immunostimulators and subunit...

Association of prior HPV vaccination with reduced preterm birth: A population based study.

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Lawton, Beverley; Howe, Anna S; Turner, Nikki; Filoche, Sara; Slatter, Tania; Devenish, Celia; Hung, Noelyn Anne

2018-01-02

Emerging evidence suggests that HPV infection is associated with negative pregnancy outcomes such as preterm birth (PTB), and pre-eclampsia. We aimed to determine if prior HPV vaccination reduced adverse pregnancy outcomes. A New Zealand population-based retrospective study linking first pregnancy outcome data (2008-2014 n = 35,646) with prior quadrivalent HPV vaccination status. Primary outcomes were likelihood (odds ratios, ORs) of PTB, pre-eclampsia, and stillbirth. Exposure groups were based on HPV vaccination. Adjusted ORs were calculated for each outcome, controlling for mother's age at delivery, ethnicity, socioeconomic status, health board region at time of delivery, and body mass index and smoking status at time of registration with maternity care provider. Mother's mean age at delivery was 19 (SD 2.1) years. Of 34,994 the pregnancies included in the final study analyses 62.3% of women were unvaccinated, 11.0% vaccinated with one or two doses and 27.7% vaccinated with three doses prior to pregnancy. PTB (OR: 0.87; CI 0.78, 0.96)) was significantly lower for women who previously received the HPV vaccine. A dose response effect was found with each successive dose received decreasing the likelihood of PTB. No associations between the vaccinated and unvaccinated groups were shown for pre-eclampsia or stillbirth. Prior receipt of the quadrivalent HPV vaccine was associated with a significant reduction in PTB (13%); suggesting that HPV vaccination may be effective in reducing PTB. The potential global public health impact is considerable and there is urgency to undertake further research to replicate and explore these findings. Copyright © 2017 Elsevier Ltd. All rights reserved.

Viral vector-based influenza vaccines

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de Vries, Rory D.; Rimmelzwaan, Guus F.

2016-01-01

ABSTRACT Antigenic drift of seasonal influenza viruses and the occasional introduction of influenza viruses of novel subtypes into the human population complicate the timely production of effective vaccines that antigenically match the virus strains that cause epidemic or pandemic outbreaks. The development of game-changing vaccines that induce broadly protective immunity against a wide variety of influenza viruses is an unmet need, in which recombinant viral vectors may provide. Use of viral vectors allows the delivery of any influenza virus antigen, or derivative thereof, to the immune system, resulting in the optimal induction of virus-specific B- and T-cell responses against this antigen of choice. This systematic review discusses results obtained with vectored influenza virus vaccines and advantages and disadvantages of the currently available viral vectors. PMID:27455345

Childhood vaccine refusal and hesitancy intentions in Croatia: insights from a population-based study.

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Repalust, Anja; Šević, Sandra; Rihtar, Stanko; Štulhofer, Aleksandar

2017-10-01

Considering that programmatic data suggest a recent rise in vaccine refusal in Croatia, this study, first of its kind in Southeast Europe, aimed to estimate the prevalence, and sociodemographic, and sociocultural determinants of childhood vaccine refusal and hesitancy (CVRH) intentions among Croatian adults. Multi-stage stratified population-based survey included 1000 individuals aged 18-88 years (M age  = 47.7, SD = 17.8), of whom 51.7% were women. The outcome, a categorical indicator, distinguished among individuals who would approve vaccinating their children (vaccine accepting), those who would approve some but not all vaccines (vaccine hesitant), and those who would refuse vaccination (vaccine refusing). A sizeable minority of participants was characterized by childhood vaccine refusal (10.6%) and hesitancy intentions (19.5%). In a multivariate assessment controlling for parenthood, the odds of vaccine hesitancy were significantly increased by a younger age (AOR = 1.96-3.03, p Croatia. Following the social contagion model, future research should move beyond individual-level approach and take into account social interaction and social network effects.

Acute disseminated encephalomyelitis onset: evaluation based on vaccine adverse events reporting systems.

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Paolo Pellegrino

Full Text Available OBJECTIVE: To evaluate epidemiological features of post vaccine acute disseminated encephalomyelitis (ADEM by considering data from different pharmacovigilance surveillance systems. METHODS: The Vaccine Adverse Event Reporting System (VAERS database and the EudraVigilance post-authorisation module (EVPM were searched to identify post vaccine ADEM cases. Epidemiological features including sex and related vaccines were analysed. RESULTS: We retrieved 205 and 236 ADEM cases from the EVPM and VAERS databases, respectively, of which 404 were considered for epidemiological analysis following verification and causality assessment. Half of the patients had less than 18 years and with a slight male predominance. The time interval from vaccination to ADEM onset was 2-30 days in 61% of the cases. Vaccine against seasonal flu and human papilloma virus vaccine were those most frequently associated with ADEM, accounting for almost 30% of the total cases. Mean number of reports per year between 2005 and 2012 in VAERS database was 40±21.7, decreasing after 2010 mainly because of a reduction of reports associated with human papilloma virus and Diphtheria, Pertussis, Tetanus, Polio and Haemophilus Influentiae type B vaccines. CONCLUSIONS: This study has a high epidemiological power as it is based on information on adverse events having occurred in over one billion people. It suffers from lack of rigorous case verification due to the weakness intrinsic to the surveillance databases used. At variance with previous reports on a prevalence of ADEM in childhood we demonstrate that it may occur at any age when post vaccination. This study also shows that the diminishing trend in post vaccine ADEM reporting related to Diphtheria, Pertussis, Tetanus, Polio and Haemophilus Influentiae type B and human papilloma virus vaccine groups is most likely not [corrected] due to a decline in vaccine coverage indicative of a reduced attention to this adverse drug reaction.

A Novel Virus-Like Particle Based Vaccine Platform Displaying the Placental Malaria Antigen VAR2CSA.

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Susan Thrane

Full Text Available Placental malaria caused by Plasmodium falciparum is a major cause of mortality and severe morbidity. Clinical testing of a soluble protein-based vaccine containing the parasite ligand, VAR2CSA, has been initiated. VAR2CSA binds to the human receptor chondroitin sulphate A (CSA and is responsible for sequestration of Plasmodium falciparum infected erythrocytes in the placenta. It is imperative that a vaccine against malaria in pregnancy, if administered to women before they become pregnant, can induce a strong and long lasting immune response. While most soluble protein-based vaccines have failed during clinical testing, virus-like particle (VLP based vaccines (e.g., the licensed human papillomavirus vaccines have demonstrated high efficacy, suggesting that the spatial assembly of the vaccine antigen is a critical parameter for inducing an optimal long-lasting protective immune response. We have developed a VLP vaccine display platform by identifying regions of the HPV16 L1 coat protein where a biotin acceptor site (AviTagTM can be inserted without compromising VLP-assembly. Subsequent biotinylation of Avi-L1 VLPs allow us to anchor monovalent streptavidin (mSA-fused proteins to the biotin, thereby obtaining a dense and repetitive VLP-display of the vaccine antigen. The mSA-VAR2CSA antigen was delivered on the Avi-L1 VLP platform and tested in C57BL/6 mice in comparison to two soluble protein-based vaccines consisting of naked VAR2CSA and mSA-VAR2CSA. The mSA-VAR2CSA Avi-L1 VLP and soluble mSA-VAR2CSA vaccines induced higher antibody titers than the soluble naked VAR2CSA vaccine after three immunizations. The VAR2CSA Avi-L1 VLP vaccine induced statistically significantly higher endpoint titres compared to the soluble mSA-VAR2CSA vaccine, after 1st and 2nd immunization; however, this difference was not statistically significant after 3rd immunization. Importantly, the VLP-VAR2CSA induced antibodies were functional in inhibiting the binding of

Learning from Successful School-based Vaccination Clinics during 2009 pH1N1

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Klaiman, Tamar; O'Connell, Katherine; Stoto, Michael A.

2014-01-01

Background: The 2009 H1N1 vaccination campaign was the largest in US history. State health departments received vaccines from the federal government and sent them to local health departments (LHDs) who were responsible for getting vaccines to the public. Many LHD's used school-based clinics to ensure children were the first to receive limited…

Muc1 based breast cancer vaccines: role of post translational modifications

International Nuclear Information System (INIS)

Begum, M.; Khurshid, R.; Nagra, S.A.

2008-01-01

Vaccine development is one of the most promising fields in cancer research. After autologous transplantation, due to low tumour burden, patients are more likely to respond immunologically to a cancer vaccine. MUC1 with its adhesive and anti adhesive functions, immunostimulatory and immunosuppressive activities, is therefore a good candidate for breast cancer vaccine. A structure-based insight into the immunogenicity of natural MUC1 glyco forms, of its sub-domains, motifs and post translational modification like glycosylation and myriostoylation may aid the design of tumour vaccines. Primary sequences of human MUC1 were retrieved from the SWISSPROT data bank. Protein pattern search: The primary sequence of Human MUC1 was searched at PROSITE (a dictionary of protein sites and patterns) database. Our study observes that post-translational modifications play an important role in presenting MUC1 as a candidate for breast cancer vaccine. It is found that the phosphorylation and glycosylation of important functional motifs of MUC1 may take part in the production of cytokines that may provide immunization. (author)

Informing vaccine decision-making: A strategic multi-attribute ranking tool for vaccines-SMART Vaccines 2.0.

Science.gov (United States)

Knobler, Stacey; Bok, Karin; Gellin, Bruce

2017-01-20

SMART Vaccines 2.0 software is being developed to support decision-making among multiple stakeholders in the process of prioritizing investments to optimize the outcomes of vaccine development and deployment. Vaccines and associated vaccination programs are one of the most successful and effective public health interventions to prevent communicable diseases and vaccine researchers are continually working towards expanding targets for communicable and non-communicable diseases through preventive and therapeutic modes. A growing body of evidence on emerging vaccine technologies, trends in disease burden, costs associated with vaccine development and deployment, and benefits derived from disease prevention through vaccination and a range of other factors can inform decision-making and investment in new and improved vaccines and targeted utilization of already existing vaccines. Recognizing that an array of inputs influences these decisions, the strategic multi-attribute ranking method for vaccines (SMART Vaccines 2.0) is in development as a web-based tool-modified from a U.S. Institute of Medicine Committee effort (IOM, 2015)-to highlight data needs and create transparency to facilitate dialogue and information-sharing among decision-makers and to optimize the investment of resources leading to improved health outcomes. Current development efforts of the SMART Vaccines 2.0 framework seek to generate a weighted recommendation on vaccine development or vaccination priorities based on population, disease, economic, and vaccine-specific data in combination with individual preference and weights of user-selected attributes incorporating valuations of health, economics, demographics, public concern, scientific and business, programmatic, and political considerations. Further development of the design and utility of the tool is being carried out by the National Vaccine Program Office of the Department of Health and Human Services and the Fogarty International Center of the

Using magnetic resonance imaging to evaluate dendritic cell-based vaccination.

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Peter M Ferguson

Full Text Available Cancer immunotherapy with antigen-loaded dendritic cell-based vaccines can induce clinical responses in some patients, but further optimization is required to unlock the full potential of this strategy in the clinic. Optimization is dependent on being able to monitor the cellular events that take place once the dendritic cells have been injected in vivo, and to establish whether antigen-specific immune responses to the tumour have been induced. Here we describe the use of magnetic resonance imaging (MRI as a simple, non-invasive approach to evaluate vaccine success. By loading the dendritic cells with highly magnetic iron nanoparticles it is possible to assess whether the injected cells drain to the lymph nodes. It is also possible to establish whether an antigen-specific response is initiated by assessing migration of successive rounds of antigen-loaded dendritic cells; in the face of a successfully primed cytotoxic response, the bulk of antigen-loaded cells are eradicated on-route to the node, whereas cells without antigen can reach the node unchecked. It is also possible to verify the induction of a vaccine-induced response by simply monitoring increases in draining lymph node size as a consequence of vaccine-induced lymphocyte trapping, which is an antigen-specific response that becomes more pronounced with repeated vaccination. Overall, these MRI techniques can provide useful early feedback on vaccination strategies, and could also be used in decision making to select responders from non-responders early in therapy.

Antigenic specificity of a monovalent versus polyvalent MOMP based Chlamydia pecorum vaccine in koalas (Phascolarctos cinereus).

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Kollipara, Avinash; Wan, Charles; Rawlinson, Galit; Brumm, Jacqui; Nilsson, Karen; Polkinghorne, Adam; Beagley, Kenneth; Timms, Peter

2013-02-06

Chlamydia continues to be a major pathogen of koalas. The bacterium is associated with ocular, respiratory and urogenital tract infections and a vaccine is considered the best option to limit the decline of mainland koala populations. Over the last 20 years, efforts to develop a chlamydial vaccine in humans have focussed on the use of the chlamydial major outer membrane protein (MOMP). Potential problems with the use of MOMP-based vaccines relate to the wide range of genetic diversity in its four variable domains. In the present study, we evaluated the immune response of koalas vaccinated with a MOMP-based C. pecorum vaccine formulated with genetically and serologically diverse MOMPs. Animals immunised with individual MOMPs developed strong antibody and lymphocyte proliferation responses to both homologous as well as heterologous MOMP proteins. Importantly, we also showed that vaccine induced antibodies which effectively neutralised various heterologous strains of koala C. pecorum in an in vitro assay. Finally, we also demonstrated that the immune responses in monovalent as well as polyvalent MOMP vaccine groups were able to recognise whole chlamydial elementary bodies, illustrating the feasibility of developing an effective MOMP based C. pecorum vaccine that could protect against a range of strains. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

RNA-Based Vaccines in Cancer Immunotherapy

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Megan A. McNamara

2015-01-01

Full Text Available RNA vaccines traditionally consist of messenger RNA synthesized by in vitro transcription using a bacteriophage RNA polymerase and template DNA that encodes the antigen(s of interest. Once administered and internalized by host cells, the mRNA transcripts are translated directly in the cytoplasm and then the resulting antigens are presented to antigen presenting cells to stimulate an immune response. Alternatively, dendritic cells can be loaded with either tumor associated antigen mRNA or total tumor RNA and delivered to the host to elicit a specific immune response. In this review, we will explain why RNA vaccines represent an attractive platform for cancer immunotherapy, discuss modifications to RNA structure that have been developed to optimize mRNA vaccine stability and translational efficiency, and describe strategies for nonviral delivery of mRNA vaccines, highlighting key preclinical and clinical data related to cancer immunotherapy.

Lessons from pandemic influenza A(H1N1): the research-based vaccine industry's perspective.

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Abelin, Atika; Colegate, Tony; Gardner, Stephen; Hehme, Norbert; Palache, Abraham

2011-02-01

As A(H1N1) influenza enters the post-pandemic phase, health authorities around the world are reviewing the response to the pandemic. To ensure this process enhances future preparations, it is essential that perspectives are included from all relevant stakeholders, including vaccine manufacturers. This paper outlines the contribution of R&D-based influenza vaccine producers to the pandemic response, and explores lessons that can be learned to improve future preparedness. The emergence of 2009 A(H1N1) influenza led to unprecedented collaboration between global health authorities, scientists and manufacturers, resulting in the most comprehensive pandemic response ever undertaken, with a number of vaccines approved for use three months after the pandemic declaration. This response was only possible because of the extensive preparations undertaken during the last decade. During this period, manufacturers greatly increased influenza vaccine production capacity, and estimates suggest a further doubling of capacity by 2014. Producers also introduced cell-culture technology, while adjuvant and whole virion technologies significantly reduced pandemic vaccine antigen content. This substantially increased pandemic vaccine production capacity, which in July 2009 WHO estimated reached 4.9 billion doses per annum. Manufacturers also worked with health authorities to establish risk management plans for robust vaccine surveillance during the pandemic. Individual producers pledged significant donations of vaccine doses and tiered-pricing approaches for developing country supply. Based on the pandemic experience, a number of improvements would strengthen future preparedness. Technical improvements to rapidly select optimal vaccine viruses, and processes to speed up vaccine standardization, could accelerate and extend vaccine availability. Establishing vaccine supply agreements beforehand would avoid the need for complex discussions during a period of intense time pressure. Enhancing

Prophylactic effect of a therapeutic vaccine against TB based on fragments of Mycobacterium tuberculosis.

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Vilaplana, Cristina; Gil, Olga; Cáceres, Neus; Pinto, Sergio; Díaz, Jorge; Cardona, Pere-Joan

2011-01-01

The prophylactic capacity of the RUTI® vaccine, based on fragmented cells of Mycobacterium tuberculosis, has been evaluated in respect to aerosol challenge with virulent bacilli. Subcutaneous vaccination significantly reduced viable bacterial counts in both lungs and spleens of C57Bl mice, when challenged 4 weeks after vaccination. RUTI® protected the spleen less than BCG. Following a 9 month vaccination-challenge interval, protection was observed for the lungs, but not for the spleen. Survival of infected guinea pigs was prolonged by vaccination given 5 weeks before challenge. Inoculations of RUTI® shortly after infection significantly reduced the viable bacterial counts in the lungs, when compared with infected control mice. Thus, vaccination by RUTI® has potential for both the prophylaxis and immunotherapy of tuberculosis.

Increased immunogenicity of recombinant Ad35-based malaria vaccine through formulation with aluminium phosphate adjuvant

NARCIS (Netherlands)

Ophorst, Olga J. A. E.; Radosevic, Katarina; Klap, Jaco M.; Sijtsma, Jeroen; Gillissen, Gert; Mintardjo, Ratna; van Ooij, Mark J. M.; Holterman, Lennart; Companjen, Arjen; Goudsmit, Jaap; Havenga, Menzo J. E.

2007-01-01

Previously, we have shown the potency of recombinant Adenovirus serotype 35 viral vaccines (rAd35) to induce strong immune response against the circumsporozoite protein (CS) of the plasmodium parasite. To further optimize immunogenicity of Ad35-based malaria vaccines we formulated rAd35.CS vaccine

An Adenoviral Vector Based Vaccine for Rhodococcus equi.

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Carla Giles

Full Text Available Rhodococcus equi is a respiratory pathogen which primarily infects foals and is endemic on farms around the world with 50% mortality and 80% morbidity in affected foals. Unless detected early and treated appropriately the disease can be fatal. Currently, there is no vaccine available to prevent this disease. For decades researchers have endeavoured to develop an effective vaccine to no avail. In this study a novel human adenoviral vector vaccine for R. equi was developed and tested in the mouse model. This vaccine generated a strong antibody and cytokine response and clearance of R. equi was demonstrated following challenge. These results show that this vaccine could potentially be developed further for use as a vaccine to prevent R. equi disease in foals.

Typhoid fever vaccination strategies.

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Date, Kashmira A; Bentsi-Enchill, Adwoa; Marks, Florian; Fox, Kimberley

2015-06-19

Typhoid vaccination is an important component of typhoid fever prevention and control, and is recommended for public health programmatic use in both endemic and outbreak settings. We reviewed experiences with various vaccination strategies using the currently available typhoid vaccines (injectable Vi polysaccharide vaccine [ViPS], oral Ty21a vaccine, and injectable typhoid conjugate vaccine [TCV]). We assessed the rationale, acceptability, effectiveness, impact and implementation lessons of these strategies to inform effective typhoid vaccination strategies for the future. Vaccination strategies were categorized by vaccine disease control strategy (preemptive use for endemic disease or to prevent an outbreak, and reactive use for outbreak control) and vaccine delivery strategy (community-based routine, community-based campaign and school-based). Almost all public health typhoid vaccination programs used ViPS vaccine and have been in countries of Asia, with one example in the Pacific and one experience using the Ty21a vaccine in South America. All vaccination strategies were found to be acceptable, feasible and effective in the settings evaluated; evidence of impact, where available, was strongest in endemic settings and in the short- to medium-term. Vaccination was cost-effective in high-incidence but not low-incidence settings. Experience in disaster and outbreak settings remains limited. TCVs have recently become available and none are WHO-prequalified yet; no program experience with TCVs was found in published literature. Despite the demonstrated success of several typhoid vaccination strategies, typhoid vaccines remain underused. Implementation lessons should be applied to design optimal vaccination strategies using TCVs which have several anticipated advantages, such as potential for use in infant immunization programs and longer duration of protection, over the ViPS and Ty21a vaccines for typhoid prevention and control. Copyright © 2015. Published by

Universal or Specific? A Modeling-Based Comparison of Broad-Spectrum Influenza Vaccines against Conventional, Strain-Matched Vaccines.

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Rahul Subramanian

2016-12-01

Full Text Available Despite the availability of vaccines, influenza remains a major public health challenge. A key reason is the virus capacity for immune escape: ongoing evolution allows the continual circulation of seasonal influenza, while novel influenza viruses invade the human population to cause a pandemic every few decades. Current vaccines have to be updated continually to keep up to date with this antigenic change, but emerging 'universal' vaccines-targeting more conserved components of the influenza virus-offer the potential to act across all influenza A strains and subtypes. Influenza vaccination programmes around the world are steadily increasing in their population coverage. In future, how might intensive, routine immunization with novel vaccines compare against similar mass programmes utilizing conventional vaccines? Specifically, how might novel and conventional vaccines compare, in terms of cumulative incidence and rates of antigenic evolution of seasonal influenza? What are their potential implications for the impact of pandemic emergence? Here we present a new mathematical model, capturing both transmission dynamics and antigenic evolution of influenza in a simple framework, to explore these questions. We find that, even when matched by per-dose efficacy, universal vaccines could dampen population-level transmission over several seasons to a greater extent than conventional vaccines. Moreover, by lowering opportunities for cross-protective immunity in the population, conventional vaccines could allow the increased spread of a novel pandemic strain. Conversely, universal vaccines could mitigate both seasonal and pandemic spread. However, where it is not possible to maintain annual, intensive vaccination coverage, the duration and breadth of immunity raised by universal vaccines are critical determinants of their performance relative to conventional vaccines. In future, conventional and novel vaccines are likely to play complementary roles in

Impact of Targeted Tuberculosis Vaccination Among a Mining Population in South Africa: A Model-Based Study.

Science.gov (United States)

Shrestha, Sourya; Chihota, Violet; White, Richard G; Grant, Alison D; Churchyard, Gavin J; Dowdy, David W

2017-12-15

Optimizing the use of new tools, such as vaccines, may play a crucial role in reaching global targets for tuberculosis (TB) control. Some of the most promising candidate vaccines target adults, although high-coverage mass vaccinations may be logistically more challenging among this population than among children. Vaccine-delivery strategies that target high-risk groups or settings might yield proportionally greater impact than do those that target the general population. We developed an individual-based TB transmission model representing a hypothetical population consisting of people who worked in South African gold mines or lived in associated labor-sending communities. We simulated the implementation of a postinfection adult vaccine with 60% efficacy and a mean effect duration of 10 years. We then compared the impact of a mine-targeted vaccination strategy, in which miners were vaccinated while in the mines, with that of a community-targeted strategy, in which random individuals within the labor-sending communities were vaccinated. Mine-targeted vaccination averted an estimated 0.37 TB cases per vaccine dose compared with 0.25 for community-targeted vaccination, for a relative efficacy of 1.46 (95% range, 1.13-1.91). The added benefit of mine-targeted vaccination primarily reflected the disproportionate demographic burden of TB among the population of adult males as a whole. As novel vaccines for TB are developed, venue-based vaccine delivery that targets high-risk demographic groups may improve both vaccine feasibility and the impact on transmission. © The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Peptide Vaccines for Leishmaniasis

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Rory C. F. De Brito

2018-05-01

Full Text Available Due to an increase in the incidence of leishmaniases worldwide, the development of new strategies such as prophylactic vaccines to prevent infection and decrease the disease have become a high priority. Classic vaccines against leishmaniases were based on live or attenuated parasites or their subunits. Nevertheless, the use of whole parasite or their subunits for vaccine production has numerous disadvantages. Therefore, the use of Leishmania peptides to design more specific vaccines against leishmaniases seems promising. Moreover, peptides have several benefits in comparison with other kinds of antigens, for instance, good stability, absence of potentially damaging materials, antigen low complexity, and low-cost to scale up. By contrast, peptides are poor immunogenic alone, and they need to be delivered correctly. In this context, several approaches described in this review are useful to solve these drawbacks. Approaches, such as, peptides in combination with potent adjuvants, cellular vaccinations, adenovirus, polyepitopes, or DNA vaccines have been used to develop peptide-based vaccines. Recent advancements in peptide vaccine design, chimeric, or polypeptide vaccines and nanovaccines based on particles attached or formulated with antigenic components or peptides have been increasingly employed to drive a specific immune response. In this review, we briefly summarize the old, current, and future stands on peptide-based vaccines, describing the disadvantages and benefits associated with them. We also propose possible approaches to overcome the related weaknesses of synthetic vaccines and suggest future guidelines for their development.

Peptide Vaccines for Leishmaniasis.

Science.gov (United States)

De Brito, Rory C F; Cardoso, Jamille M De O; Reis, Levi E S; Vieira, Joao F; Mathias, Fernando A S; Roatt, Bruno M; Aguiar-Soares, Rodrigo Dian D O; Ruiz, Jeronimo C; Resende, Daniela de M; Reis, Alexandre B

2018-01-01

Due to an increase in the incidence of leishmaniases worldwide, the development of new strategies such as prophylactic vaccines to prevent infection and decrease the disease have become a high priority. Classic vaccines against leishmaniases were based on live or attenuated parasites or their subunits. Nevertheless, the use of whole parasite or their subunits for vaccine production has numerous disadvantages. Therefore, the use of Leishmania peptides to design more specific vaccines against leishmaniases seems promising. Moreover, peptides have several benefits in comparison with other kinds of antigens, for instance, good stability, absence of potentially damaging materials, antigen low complexity, and low-cost to scale up. By contrast, peptides are poor immunogenic alone, and they need to be delivered correctly. In this context, several approaches described in this review are useful to solve these drawbacks. Approaches, such as, peptides in combination with potent adjuvants, cellular vaccinations, adenovirus, polyepitopes, or DNA vaccines have been used to develop peptide-based vaccines. Recent advancements in peptide vaccine design, chimeric, or polypeptide vaccines and nanovaccines based on particles attached or formulated with antigenic components or peptides have been increasingly employed to drive a specific immune response. In this review, we briefly summarize the old, current, and future stands on peptide-based vaccines, describing the disadvantages and benefits associated with them. We also propose possible approaches to overcome the related weaknesses of synthetic vaccines and suggest future guidelines for their development.

Designing Peptide-Based HIV Vaccine for Chinese

Science.gov (United States)

Fan, Xiaojuan

2014-01-01

CD4+ T cells are central to the induction and maintenance of CD8+ T cell and antibody-producing B cell responses, and the latter are essential for the protection against disease in subjects with HIV infection. How to elicit HIV-specific CD4+ T cell responses in a given population using vaccines is one of the major areas of current HIV vaccine research. To design vaccine that targets specifically Chinese, we assembled a database that is comprised of sequences from 821 Chinese HIV isolates and 46 human leukocyte antigen (HLA) DR alleles identified in Chinese population. We then predicted 20 potential HIV epitopes using bioinformatics approaches. The combination of these 20 epitopes has a theoretical coverage of 98.1% of the population for both the prevalent HIV genotypes and also Chinese HLA-DR types. We suggest that testing this vaccine experimentally will facilitate the development of a CD4+ T cell vaccine especially catered for Chinese. PMID:25136573

An M2e-based synthetic peptide vaccine for influenza A virus confers heterosubtypic protection from lethal virus challenge.

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Ma, Ji-Hong; Yang, Fu-Ru; Yu, Hai; Zhou, Yan-Jun; Li, Guo-Xin; Huang, Meng; Wen, Feng; Tong, Guangzhi

2013-07-09

Vaccination is considered as the most effective preventive method to control influenza. The hallmark of influenza virus is the remarkable variability of its major surface glycoproteins, HA and NA, which allows the virus to evade existing anti-influenza immunity in the target population. So it is necessary to develop a novel vaccine to control animal influenza virus. Also we know that the ectodomain of influenza matrix protein 2 (M2e) is highly conserved in animal influenza A viruses, so a vaccine based on the M2e could avoid several drawbacks of the traditional vaccines. In this study we designed a novel tetra-branched multiple antigenic peptide (MAP) based vaccine, which was constructed by fusing four copies of M2e to one copy of foreign T helper (Th) cell epitope, and then investigated its immune responses. Our results show that the M2e-MAP induced strong M2e-specific IgG antibody,which responses following 2 doses immunization in the presence of Freunds' adjuvant. M2e-MAP vaccination limited viral replication substantially. Also it could attenuate histopathological damage in the lungs of challenged mice and counteracted weight loss. M2e-MAP-based vaccine protected immunized mice against the lethal challenge with PR8 virus. Based on these findings, M2e-MAP-based vaccine seemed to provide useful information for the research of M2e-based influenza vaccine. Also it show huge potential to study vaccines for other similarly viruses.

Making evidence-based selections of influenza vaccines

OpenAIRE

Childress, Billy-Clyde; Montney, Joshua D; Albro, Elise A

2014-01-01

Years ago, intramuscular influenza vaccines were the only option for those who wanted to arm themselves against the flu. Today there are alternatives, including intradermal injections and intranasal sprays. In order to select the right influenza vaccine for their patients, pharmacists, and other healthcare professionals must have a basic understanding of the immune system. Influenza vaccines elicit different levels of immune response involving innate and adaptive immunity, which are critical ...

Effect of School-based Human Papillomavirus (HPV) Vaccination on ...

African Journals Online (AJOL)

AJRH Managing Editor

assessed girls' knowledge of cervical cancer and HPV vaccine, and their acceptance of future vaccination of ... studies involve parents and young adults. The ... vaccine was delivered during the routine Child ... and attitudes about the vaccine.

Vaccination strategies for future influenza pandemics: a severity-based cost effectiveness analysis.

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Kelso, Joel K; Halder, Nilimesh; Milne, George J

2013-02-11

A critical issue in planning pandemic influenza mitigation strategies is the delay between the arrival of the pandemic in a community and the availability of an effective vaccine. The likely scenario, born out in the 2009 pandemic, is that a newly emerged influenza pandemic will have spread to most parts of the world before a vaccine matched to the pandemic strain is produced. For a severe pandemic, additional rapidly activated intervention measures will be required if high mortality rates are to be avoided. A simulation modelling study was conducted to examine the effectiveness and cost effectiveness of plausible combinations of social distancing, antiviral and vaccination interventions, assuming a delay of 6-months between arrival of an influenza pandemic and first availability of a vaccine. Three different pandemic scenarios were examined; mild, moderate and extreme, based on estimates of transmissibility and pathogenicity of the 2009, 1957 and 1918 influenza pandemics respectively. A range of different durations of social distancing were examined, and the sensitivity of the results to variation in the vaccination delay, ranging from 2 to 6 months, was analysed. Vaccination-only strategies were not cost effective for any pandemic scenario, saving few lives and incurring substantial vaccination costs. Vaccination coupled with long duration social distancing, antiviral treatment and antiviral prophylaxis was cost effective for moderate pandemics and extreme pandemics, where it saved lives while simultaneously reducing the total pandemic cost. Combined social distancing and antiviral interventions without vaccination were significantly less effective, since without vaccination a resurgence in case numbers occurred as soon as social distancing interventions were relaxed. When social distancing interventions were continued until at least the start of the vaccination campaign, attack rates and total costs were significantly lower, and increased rates of vaccination

Acceptability of School-Based Health Centers for Human Papillomavirus Vaccination Visits: A Mixed-Methods Study.

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Hansen, Caitlin E; Okoloko, Edirin; Ogunbajo, Adedotun; North, Anna; Niccolai, Linda M

2017-09-01

Countries with high human papillomavirus (HPV) vaccination rates have achieved this success largely through school-based vaccination. Using school-based health centers (SBHCs) in the United States, where HPV vaccine remains underutilized, could improve uptake. In this mixed-methods study, we examined acceptability, facilitators, and barriers of HPV vaccination visits at SBHCs from the perspectives of adolescents and parents. We conducted qualitative interviews and structured surveys with adolescents and parents recruited from an urban, hospital-based clinic. Interviews with parents (N = 20) and adolescents (N = 20) were audio-recorded and transcribed for analysis using an iterative thematic approach. Quantitative measures for a survey administered to parents (N = 131) were derived from the qualitative findings. Survey results were analyzed by chi-square tests. Many participants expressed favorable opinions of HPV vaccination at SBHCs in qualitative interviews. Facilitators included convenience, ease of scheduling, and not missing work or school. However, barriers were noted including concerns about obtaining care outside the medical home, fragmentation of medical records, and negative perceptions about SBHCs. Quantitative findings revealed that a higher proportion of parents with experience using SBHCs were willing to use a middle school (59.5%) or high school (80.5%) SBHC for HPV vaccinations compared with those who had not used SBHCs (p HPV vaccination visits at SBHCs were acceptable, and SBHC users expressed more favorable attitudes. Barriers to HPV vaccination at SBHCs can be addressed through more education about SBHCs' role, and improvement of systems to coordinate care. © 2017, American School Health Association.

6-O-Branched Oligo-β-glucan-Based Antifungal Glycoconjugate Vaccines.

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Liao, Guochao; Zhou, Zhifang; Liao, Jun; Zu, Luning; Wu, Qiuye; Guo, Zhongwu

2016-02-12

With the rapid growth in fungal infections and drug-resistant fungal strains, antifungal vaccines have become an especially attractive strategy to tackle this important health problem. β-Glucans, a class of extracellular carbohydrate antigens abundantly and consistently expressed on fungal cell surfaces, are intriguing epitopes for antifungal vaccine development. β-Glucans have a conserved β-1,3-glucan backbone with sporadic β-1,3- or β-1,6-linked short glucans as branches at the 6-O-positions, and the branches may play a critical role in their immunologic functions. To study the immunologic properties of branched β-glucans and develop β-glucan-based antifungal vaccines, three branched β-glucan oligosaccharides with 6-O-linked β-1,6-tetraglucose, β-1,3-diglucose, and β-1,3-tetraglucose branches on a β-1,3-nonaglucan backbone, which mimic the structural epitopes of natural β-glucans, were synthesized and coupled with keyhole limpet hemocyanin (KLH) to form novel synthetic conjugate vaccines. These glycoconjugates were proved to elicit strong IgG antibody responses in mice. It was also discovered that the number, size, and structure of branches linked to the β-glucan backbone had a significant impact on the immunologic property. Moreover, antibodies induced by the synthetic oligosaccharide-KLH conjugates were able to recognize and bind to natural β-glucans and fungal cells. Most importantly, these conjugates elicited effective protection against systemic Candida albicans infection in mice. Thus, branched oligo-β-glucans were identified as functional epitopes for antifungal vaccine design and the corresponding protein conjugates as promising antifungal vaccine candidates.

School-based human papillomavirus vaccination: An opportunity to ...

African Journals Online (AJOL)

cational drive to improve knowledge and screening of mothers can be successful ... invited to sign consent and assent for the girl child to be vaccinated, and all mothers were .... view of the positive attitudes towards vaccines in general, vaccine.

Changes in cytokine and biomarker blood levels in patients with colorectal cancer during dendritic cell-based vaccination

DEFF Research Database (Denmark)

Burgdorf, Stefan; Claesson, Mogens; Nielsen, Hans

2009-01-01

Introduction. Immunotherapy based on dendritic cell vaccination has exciting perspectives for treatment of cancer. In order to clarify immunological mechanisms during vaccination it is essential with intensive monitoring of the responses. This may lead to optimization of treatment and prediction......-inflammatory cytokines in serum of patients who achieved stable disease following vaccination suggest the occurrence of vaccine-induced Th1 responses. Since Th1 responses seem to be essential in cancer immunotherapy this may indicate a therapeutic potential of the vaccine....... of responding patients. The aim of this study was to evaluate cytokine and biomarker responses in patients with colorectal cancer treated with a cancer vaccine based on dendritic cells pulsed with an allogeneic melanoma cell lysate. Material and methods. Plasma and serum samples were collected prior...

How to Meet the Last OIE Expert Surveillance Panel Recommendations on Equine Influenza (EI Vaccine Composition: A Review of the Process Required for the Recombinant Canarypox-Based EI Vaccine

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Romain Paillot

2016-11-01

Full Text Available Vaccination is highly effective to prevent, control, and limit the impact of equine influenza (EI, a major respiratory disease of horses. However, EI vaccines should contain relevant equine influenza virus (EIV strains for optimal protection. The OIE expert surveillance panel annually reviews EIV evolution and, since 2010, the use of Florida clade 1 and 2 sub-lineages representative vaccine strains is recommended. This report summarises the development process of a fully- updated recombinant canarypox-based EI vaccine in order to meet the last OIE recommendations, including the vaccine mode of action, production steps and schedule. The EI vaccine ProteqFlu contains 2 recombinant canarypox viruses expressing the haemagglutinin of the A/equine/Ohio/03 and A/equine/Richmond/1/07 isolates (Florida clade 1 and 2 sub-lineages, respectively. The updated EI vaccine was tested for efficacy against the representative Florida clade 2 EIV strain A/equine/Richmond/1/07 in the Welsh mountain pony model. Protective antibody response, clinical signs of disease and virus shedding were compared with unvaccinated control ponies. Significant protection was measured in vaccinated ponies, which supports the vaccine registration. The recombinant canarypox-based EI vaccine was the first fully updated EI vaccine available in the EU, which will help to minimise the increasing risk of vaccine breakdown due to constant EIV evolution through antigenic drift.

Correlates of Protection for M Protein-Based Vaccines against Group A Streptococcus

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Shu Ki Tsoi

2015-01-01

Full Text Available Group A streptococcus (GAS is known to cause a broad spectrum of illness, from pharyngitis and impetigo, to autoimmune sequelae such as rheumatic heart disease, and invasive diseases. It is a significant cause of infectious disease morbidity and mortality worldwide, but no efficacious vaccine is currently available. Progress in GAS vaccine development has been hindered by a number of obstacles, including a lack of standardization in immunoassays and the need to define human correlates of protection. In this review, we have examined the current immunoassays used in both GAS and other organisms, and explored the various challenges in their implementation in order to propose potential future directions to identify a correlate of protection and facilitate the development of M protein-based vaccines, which are currently the main GAS vaccine candidates.

Correlates of Protection for M Protein-Based Vaccines against Group A Streptococcus

Science.gov (United States)

Smeesters, Pierre R.; Frost, Hannah R. C.; Steer, Andrew C.

2015-01-01

Group A streptococcus (GAS) is known to cause a broad spectrum of illness, from pharyngitis and impetigo, to autoimmune sequelae such as rheumatic heart disease, and invasive diseases. It is a significant cause of infectious disease morbidity and mortality worldwide, but no efficacious vaccine is currently available. Progress in GAS vaccine development has been hindered by a number of obstacles, including a lack of standardization in immunoassays and the need to define human correlates of protection. In this review, we have examined the current immunoassays used in both GAS and other organisms, and explored the various challenges in their implementation in order to propose potential future directions to identify a correlate of protection and facilitate the development of M protein-based vaccines, which are currently the main GAS vaccine candidates. PMID:26101780

Peptide-based anti-PCSK9 vaccines - an approach for long-term LDLc management.

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Gergana Galabova

Full Text Available Low Density Lipoprotein (LDL hypercholesterolemia, and its associated cardiovascular diseases, are some of the leading causes of death worldwide. The ability of proprotein convertase subtilisin/kexin 9 (PCSK9 to modulate circulating LDL cholesterol (LDLc concentrations made it a very attractive target for LDLc management. To date, the most advanced approaches for PCSK9 inhibition are monoclonal antibody (mAb therapies. Although shown to lower LDLc significantly, mAbs face functional limitations because of their relatively short in vivo half-lives necessitating frequent administration. Here, we evaluated the long-term efficacy and safety of PCSK9-specific active vaccines in different preclinical models.PCSK9 peptide-based vaccines were successfully selected by our proprietary technology. To test their efficacy, wild-type (wt mice, Ldlr+/- mice, and rats were immunized with highly immunogenic vaccine candidates. Vaccines induced generation of high-affine PCSK9-specific antibodies in all species. Group mean total cholesterol (TC concentration was reduced by up to 30%, and LDLc up to 50% in treated animals. Moreover, the PCSK9 vaccine-induced humoral immune response persisted for up to one year in mice, and reduced cholesterol levels significantly throughout the study. Finally, the vaccines were well tolerated in all species tested.Peptide-based anti-PCSK9 vaccines induce the generation of antibodies that are persistent, high-affine, and functional for up to one year. They are powerful and safe tools for long-term LDLc management, and thus may represent a novel therapeutic approach for the prevention and/or treatment of LDL hypercholesterolemia-related cardiovascular diseases in humans.

Vaccinia-based influenza vaccine overcomes previously induced immunodominance hierarchy for heterosubtypic protection.

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Kwon, Ji-Sun; Yoon, Jungsoon; Kim, Yeon-Jung; Kang, Kyuho; Woo, Sunje; Jung, Dea-Im; Song, Man Ki; Kim, Eun-Ha; Kwon, Hyeok-Il; Choi, Young Ki; Kim, Jihye; Lee, Jeewon; Yoon, Yeup; Shin, Eui-Cheol; Youn, Jin-Won

2014-08-01

Growing concerns about unpredictable influenza pandemics require a broadly protective vaccine against diverse influenza strains. One of the promising approaches was a T cell-based vaccine, but the narrow breadth of T-cell immunity due to the immunodominance hierarchy established by previous influenza infection and efficacy against only mild challenge condition are important hurdles to overcome. To model T-cell immunodominance hierarchy in humans in an experimental setting, influenza-primed C57BL/6 mice were chosen and boosted with a mixture of vaccinia recombinants, individually expressing consensus sequences from avian, swine, and human isolates of influenza internal proteins. As determined by IFN-γ ELISPOT and polyfunctional cytokine secretion, the vaccinia recombinants of influenza expanded the breadth of T-cell responses to include subdominant and even minor epitopes. Vaccine groups were successfully protected against 100 LD50 challenges with PR/8/34 and highly pathogenic avian influenza H5N1, which contained the identical dominant NP366 epitope. Interestingly, in challenge with pandemic A/Cal/04/2009 containing mutations in the dominant epitope, only the group vaccinated with rVV-NP + PA showed improved protection. Taken together, a vaccinia-based influenza vaccine expressing conserved internal proteins improved the breadth of influenza-specific T-cell immunity and provided heterosubtypic protection against immunologically close as well as distant influenza strains. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Quality of Web-Based Educational Interventions for Clinicians on Human Papillomavirus Vaccine: Content and Usability Assessment.

Science.gov (United States)

Rosen, Brittany L; Bishop, James M; McDonald, Skye L; Kahn, Jessica A; Kreps, Gary L

2018-02-16

Human papillomavirus (HPV) vaccination rates fall far short of Healthy People 2020 objectives. A leading reason is that clinicians do not recommend the vaccine consistently and strongly to girls and boys in the age group recommended for vaccination. Although Web-based HPV vaccine educational interventions for clinicians have been created to promote vaccination recommendations, rigorous evaluations of these interventions have not been conducted. Such evaluations are important to maximize the efficacy of educational interventions in promoting clinician recommendations for HPV vaccination. The objectives of our study were (1) to expand previous research by systematically identifying HPV vaccine Web-based educational interventions developed for clinicians and (2) to evaluate the quality of these Web-based educational interventions as defined by access, content, design, user evaluation, interactivity, and use of theory or models to create the interventions. Current HPV vaccine Web-based educational interventions were identified from general search engines (ie, Google), continuing medical education search engines, health department websites, and professional organization websites. Web-based educational interventions were included if they were created for clinicians (defined as individuals qualified to deliver health care services, such as physicians, clinical nurses, and school nurses, to patients aged 9 to 26 years), delivered information about the HPV vaccine and how to increase vaccination rates, and provided continuing education credits. The interventions' content and usability were analyzed using 6 key indicators: access, content, design, evaluation, interactivity, and use of theory or models. A total of 21 interventions were identified, out of which 7 (33%) were webinars, 7 (33%) were videos or lectures, and 7 (33%) were other (eg, text articles, website modules). Of the 21 interventions, 17 (81%) identified the purpose of the intervention, 12 (57%) provided the

History of vaccination.

Science.gov (United States)

Plotkin, Stanley

2014-08-26

Vaccines have a history that started late in the 18th century. From the late 19th century, vaccines could be developed in the laboratory. However, in the 20th century, it became possible to develop vaccines based on immunologic markers. In the 21st century, molecular biology permits vaccine development that was not possible before.

History of vaccination

OpenAIRE

Plotkin, Stanley

2014-01-01

Vaccines have a history that started late in the 18th century. From the late 19th century, vaccines could be developed in the laboratory. However, in the 20th century, it became possible to develop vaccines based on immunologic markers. In the 21st century, molecular biology permits vaccine development that was not possible before.

An update on safety and immunogenicity of vaccines containing emulsion-based adjuvants.

Science.gov (United States)

Fox, Christopher B; Haensler, Jean

2013-07-01

With the exception of alum, emulsion-based vaccine adjuvants have been administered to far more people than any other adjuvant, especially since the 2009 H1N1 influenza pandemic. The number of clinical safety and immunogenicity evaluations of vaccines containing emulsion adjuvants has correspondingly mushroomed. In this review, the authors introduce emulsion adjuvant composition and history before detailing the most recent findings from clinical and postmarketing data regarding the effects of emulsion adjuvants on vaccine immunogenicity and safety, with emphasis on the most widely distributed emulsion adjuvants, MF59® and AS03. The authors also present a summary of other emulsion adjuvants in clinical development and indicate promising avenues for future emulsion-based adjuvant development. Overall, emulsion adjuvants have demonstrated potent adjuvant activity across a number of disease indications along with acceptable safety profiles.

Vaccination: Developing and implementing a competency-based-curriculum at the Medical Faculty of LMU Munich

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Vogel, B.

2016-02-01

Full Text Available Background: In Germany medical students should gain proficiency and specific skills in the vaccination field. Especially important is the efficient communication of scientific results about vaccinations to the community, in order to give professional counseling with a complete overview about therapeutic options.Aim of the project: The aim of this project is to set up a vaccination-related curriculum in the Medical Faculty at the Ludwig-Maximilians-University in Munich. The structure of the curriculum is based on the National catalogue for competency-based learning objectives in the field of vaccination (Nationaler Kompetenzbasierter Lernzielekatalog Medizin NKLM. Through this curriculum, the students will not only acquire the classical educational skills concerning vaccination in theory and practice, but they will also learn how to become independent in the decision-making process and counseling. Moreover, the students will become aware of consequences of action related to this specific topic.Methods: According to defined guidelines, an analysis was performed on courses, which are currently offered by the university. A separate analysis of the NKLM was carried out. Both analyses identified the active courses related to the topic of vaccination as well as the NKLM learning objectives. The match between the topics taught in current courses and the NKLM learning objectives identified gaps concerning the teaching of specific content. Courses were modified in order to implement the missing NKLM learning objectives.Results: These analyses identified 24 vaccination-related courses, which are currently taught at the University. Meanwhile, 35 learning objectives on vaccination were identified in the NKLM catalogue. Four of which were identified as not yet part of the teaching program. In summary, this interdisciplinary work enabled the development of a new vaccination-related curriculum, including 35 learning objectives, which are now implemented in

Nasal delivery of an adenovirus-based vaccine bypasses pre-existing immunity to the vaccine carrier and improves the immune response in mice.

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Maria A Croyle

Full Text Available Pre-existing immunity to human adenovirus serotype 5 (Ad5 is common in the general population. Bypassing pre-existing immunity could maximize Ad5 vaccine efficacy. Vaccination by the intramuscular (I.M., nasal (I.N. or oral (P.O. route with Ad5 expressing Ebola Zaire glycoprotein (Ad5-ZGP fully protected naïve mice against lethal challenge with Ebola. In the presence of pre-existing immunity, only mice vaccinated I.N. survived. The frequency of IFN-gamma+ CD8+ T cells was reduced by 80% and by 15% in animals vaccinated by the I.M. and P.O. routes respectively. Neutralizing antibodies could not be detected in serum from either treatment group. Pre-existing immunity did not compromise the frequency of IFN-gamma+ CD8+ T cells (3.9+/-1% naïve vs. 3.6+/-1% pre-existing immunity, PEI nor anti-Ebola neutralizing antibody (NAB, 40+/-10 reciprocal dilution, both groups. The number of INF-gamma+ CD8+ cells detected in bronchioalveolar lavage fluid (BAL after I.N. immunization was not compromised by pre-existing immunity to Ad5 (146+/-14, naïve vs. 120+/-16 SFC/million MNCs, PEI. However, pre-existing immunity reduced NAB levels in BAL by approximately 25% in this group. To improve the immune response after oral vaccination, the Ad5-based vaccine was PEGylated. Mice given the modified vaccine did not survive challenge and had reduced levels of IFN-gamma+ CD8+ T cells 10 days after administration (0.3+/-0.3% PEG vs. 1.7+/-0.5% unmodified. PEGylation did increase NAB levels 2-fold. These results provide some insight about the degree of T and B cell mediated immunity necessary for protection against Ebola virus and suggest that modification of the virus capsid can influence the type of immune response elicited by an Ad5-based vaccine.

A replicating cytomegalovirus-based vaccine encoding a single Ebola virus nucleoprotein CTL epitope confers protection against Ebola virus.

Directory of Open Access Journals (Sweden)

Yoshimi Tsuda

2011-08-01

Full Text Available Human outbreaks of Ebola virus (EBOV are a serious human health concern in Central Africa. Great apes (gorillas/chimpanzees are an important source of EBOV transmission to humans due to increased hunting of wildlife including the 'bush-meat' trade. Cytomegalovirus (CMV is an highly immunogenic virus that has shown recent utility as a vaccine platform. CMV-based vaccines also have the unique potential to re-infect and disseminate through target populations regardless of prior CMV immunity, which may be ideal for achieving high vaccine coverage in inaccessible populations such as great apes.We hypothesize that a vaccine strategy using CMV-based vectors expressing EBOV antigens may be ideally suited for use in inaccessible wildlife populations. To establish a 'proof-of-concept' for CMV-based vaccines against EBOV, we constructed a mouse CMV (MCMV vector expressing a CD8+ T cell epitope from the nucleoprotein (NP of Zaire ebolavirus (ZEBOV (MCMV/ZEBOV-NP(CTL. MCMV/ZEBOV-NP(CTL induced high levels of long-lasting (>8 months CD8+ T cells against ZEBOV NP in mice. Importantly, all vaccinated animals were protected against lethal ZEBOV challenge. Low levels of anti-ZEBOV antibodies were only sporadically detected in vaccinated animals prior to ZEBOV challenge suggesting a role, at least in part, for T cells in protection.This study demonstrates the ability of a CMV-based vaccine approach to protect against an highly virulent human pathogen, and supports the potential for 'disseminating' CMV-based EBOV vaccines to prevent EBOV transmission in wildlife populations.

Development of Cytomegalovirus-Based Vaccines Against Melanoma

Science.gov (United States)

2016-10-01

Efficacy will be examined in mice by vaccination at 7, 14, and 21 days after tumor induction through monitoring tumor incidence, size, survival...intradermal B16 solid tumor model. Mice were inoculated with B16F10 and 3 days later were vaccinated with MCMVgp100KGP. For one experiment, mice were...We are now comparing the efficacy of this new vaccine to other single epitope virus vectors. Q6. can you please also clarify the AIMS of the SPARK

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

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Melissa B Gilkey

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

Pre-clinical efficacy and safety of experimental vaccines based on non-replicating vaccinia vectors against yellow fever.

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Birgit Schäfer

Full Text Available BACKGROUND: Currently existing yellow fever (YF vaccines are based on the live attenuated yellow fever virus 17D strain (YFV-17D. Although, a good safety profile was historically attributed to the 17D vaccine, serious adverse events have been reported, making the development of a safer, more modern vaccine desirable. METHODOLOGY/PRINCIPAL FINDINGS: A gene encoding the precursor of the membrane and envelope (prME protein of the YFV-17D strain was inserted into the non-replicating modified vaccinia virus Ankara and into the D4R-defective vaccinia virus. Candidate vaccines based on the recombinant vaccinia viruses were assessed for immunogenicity and protection in a mouse model and compared to the commercial YFV-17D vaccine. The recombinant live vaccines induced γ-interferon-secreting CD4- and functionally active CD8-T cells, and conferred full protection against lethal challenge already after a single low immunization dose of 10(5 TCID(50. Surprisingly, pre-existing immunity against wild-type vaccinia virus did not negatively influence protection. Unlike the classical 17D vaccine, the vaccinia virus-based vaccines did not cause mortality following intracerebral administration in mice, demonstrating better safety profiles. CONCLUSIONS/SIGNIFICANCE: The non-replicating recombinant YF candidate live vaccines induced a broad immune response after single dose administration, were effective even in the presence of a pre-existing immunity against vaccinia virus and demonstrated an excellent safety profile in mice.

Pre-Clinical Efficacy and Safety of Experimental Vaccines Based on Non-Replicating Vaccinia Vectors against Yellow Fever

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Schäfer, Birgit; Holzer, Georg W.; Joachimsthaler, Alexandra; Coulibaly, Sogue; Schwendinger, Michael; Crowe, Brian A.; Kreil, Thomas R.; Barrett, P. Noel; Falkner, Falko G.

2011-01-01

Background Currently existing yellow fever (YF) vaccines are based on the live attenuated yellow fever virus 17D strain (YFV-17D). Although, a good safety profile was historically attributed to the 17D vaccine, serious adverse events have been reported, making the development of a safer, more modern vaccine desirable. Methodology/Principal Findings A gene encoding the precursor of the membrane and envelope (prME) protein of the YFV-17D strain was inserted into the non-replicating modified vaccinia virus Ankara and into the D4R-defective vaccinia virus. Candidate vaccines based on the recombinant vaccinia viruses were assessed for immunogenicity and protection in a mouse model and compared to the commercial YFV-17D vaccine. The recombinant live vaccines induced γ-interferon-secreting CD4- and functionally active CD8-T cells, and conferred full protection against lethal challenge already after a single low immunization dose of 105 TCID50. Surprisingly, pre-existing immunity against wild-type vaccinia virus did not negatively influence protection. Unlike the classical 17D vaccine, the vaccinia virus-based vaccines did not cause mortality following intracerebral administration in mice, demonstrating better safety profiles. Conclusions/Significance The non-replicating recombinant YF candidate live vaccines induced a broad immune response after single dose administration, were effective even in the presence of a pre-existing immunity against vaccinia virus and demonstrated an excellent safety profile in mice. PMID:21931732

Epitope mapping: the first step in developing epitope-based vaccines.

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Gershoni, Jonathan M; Roitburd-Berman, Anna; Siman-Tov, Dror D; Tarnovitski Freund, Natalia; Weiss, Yael

2007-01-01

Antibodies are an effective line of defense in preventing infectious diseases. Highly potent neutralizing antibodies can intercept a virus before it attaches to its target cell and, thus, inactivate it. This ability is based on the antibodies' specific recognition of epitopes, the sites of the antigen to which antibodies bind. Thus, understanding the antibody/epitope interaction provides a basis for the rational design of preventive vaccines. It is assumed that immunization with the precise epitope, corresponding to an effective neutralizing antibody, would elicit the generation of similarly potent antibodies in the vaccinee. Such a vaccine would be a 'B-cell epitope-based vaccine', the implementation of which requires the ability to backtrack from a desired antibody to its corresponding epitope. In this article we discuss a range of methods that enable epitope discovery based on a specific antibody. Such a reversed immunological approach is the first step in the rational design of an epitope-based vaccine. Undoubtedly, the gold standard for epitope definition is x-ray analyses of crystals of antigen:antibody complexes. This method provides atomic resolution of the epitope; however, it is not readily applicable to many antigens and antibodies, and requires a very high degree of sophistication and expertise. Most other methods rely on the ability to monitor the binding of the antibody to antigen fragments or mutated variations. In mutagenesis of the antigen, loss of binding due to point modification of an amino acid residue is often considered an indication of an epitope component. In addition, computational combinatorial methods for epitope mapping are also useful. These methods rely on the ability of the antibody of interest to affinity isolate specific short peptides from combinatorial phage display peptide libraries. The peptides are then regarded as leads for the definition of the epitope corresponding to the antibody used to screen the peptide library. For

Recent advances in recombinant protein-based malaria vaccines

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Draper, Simon J; Angov, Evelina; Horii, Toshihiro

2015-01-01

Plasmodium parasites are the causative agent of human malaria, and the development of a highly effective vaccine against infection, disease and transmission remains a key priority. It is widely established that multiple stages of the parasite's complex lifecycle within the human host and mosquito...... vector are susceptible to vaccine-induced antibodies. The mainstay approach to antibody induction by subunit vaccination has been the delivery of protein antigen formulated in adjuvant. Extensive efforts have been made in this endeavor with respect to malaria vaccine development, especially with regard......, with the prospects for the development of a highly effective multi-component/multi-stage/multi-antigen formulation seeming ever more likely. This review will focus on recent progress in protein vaccine design, development and/or clinical testing for a number of leading malaria antigens from the sporozoite...

Low prevalence of vaccine-type HPV infections in young women following the implementation of a school-based and catch-up vaccination in Quebec, Canada.

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Goggin, P; Sauvageau, C; Gilca, V; Defay, F; Lambert, G; Mathieu-C, S; Guenoun, J; Comète, E; Coutlée, F

2018-01-02

In Quebec, Canada, a school-based HPV vaccination for girls has been offered since 2008. The vaccine used in the program targets HPV16/18, responsible for ∼70% of cervical cancers and HPV6/11, responsible for the majority of anogenital warts. The objective of this study was to assess the prevalence of HPV in vaccinated and unvaccinated women. Women aged 17-29 years were eligible to participate. Participants' age, vaccination status and diverse risk factors were assessed by a computer-assisted questionnaire. Biological specimens were obtained by self-sampling. HPV genotyping was performed by Linear Array. A total of 2,118 women were recruited. 2,042 completed the questionnaire and 1,937 provided a vaginal sample. Vaccination coverage varied from 83.5% in women aged 17-19 to 19.1% in those aged 23-29. The overall prevalence of HPV in sexually active women was 39.4% (95%CI: 37.0-41.7) and 56.7% of infected women had multiple type infections. The prevalence of vaccine HPV types varied by age and vaccination status except for women aged 23-29 for whom similar results were observed. Vaccine HPV types were detected in 0.3%, 1.4% and 10.5% of vaccinated women aged 17-19, 20-23, and 23-29 (pHPV16 or HPV18 were detected in 10 women having received at least one dose of vaccine. Nine of these women were already sexually active at the time of vaccination. Infections with HPV types included in the vaccine are rare in women aged less than 23 years and are virtually absent in those who received at least one dose of vaccine before sexual debut.

Antitumour responses induced by a cell-based Reovirus vaccine in murine lung and melanoma models

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Campion, Ciorsdan A.; Soden, Declan; Forde, Patrick F.

2016-01-01

The ever increasing knowledge in the areas of cell biology, the immune system and the mechanisms of cancer are allowing a new phase of immunotherapy to develop. The aim of cancer vaccination is to activate the host immune system and some success has been observed particularly in the use of the BCG vaccine for bladder cancer as an immunostimulant. Reovirus, an orphan virus, has proven itself as an oncolytic virus in vitro and in vivo. Over 80 % of tumour cell lines have been found to be susceptible to Reovirus infection and it is currently in phase III clinical trials. It has been shown to induce immune responses to tumours with very low toxicities. In this study, Reovirus was examined in two main approaches in vivo, in mice, using the melanoma B16F10 and Lewis Lung Carcinoma (LLC) models. Initially, mice were treated intratumourally (IT) with Reovirus and the immune responses determined by cytokine analysis. Mice were also vaccinated using a cell-based Reovirus vaccine and subsequently exposed to a tumourigenic dose of cells (B16F10 or LLC). Using the same cell-based Reovirus vaccine, established tumours were treated and subsequent immune responses and virus retrieval investigated. Upregulation of several cytokines was observed following treatment and replication-competent virus was also retrieved from treated tumours. Varying levels of cytokine upregulation were observed and no replication-competent virus was retrieved in vaccine-treated mice. Prolongation of survival and delayed tumour growth were observed in all models and an immune response to Reovirus, either using Reovirus alone or a cell-based vaccine was also observed in all mice. This study provides evidence of immune response to tumours using a cell-based Reovirus vaccine in both tumour models investigated, B16F10 and LLC, cytokine induction was observed with prolongation of survival in almost all cases which may suggest a new method for using Reovirus in the clinic

Evaluation of an ompA-based phage-mediated DNA vaccine against Chlamydia abortus in piglets.

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Ou, Changbo; Tian, Deyu; Ling, Yong; Pan, Qing; He, Qing; Eko, Francis O; He, Cheng

2013-08-01

Chlamydia abortus (C. abortus) is an obligate intracellular pathogen that causes abortion in pigs and poses a zoonotic risk in pregnant women. Although attenuated and inactivated vaccines are available, they do not provide complete protection in animals underlining the need to develop new vaccines. In this study, we tested the hypothesis that intramuscular immunization with an ompA-based phage-mediated DNA chlamydial vaccine candidate will induce significant antigen-specific cellular and humoral immune responses. Thus, groups of piglets (five per group) were immunized intramuscularly with the phage-MOMP vaccine (λ-MOMP) or a commercial live-attenuated vaccine (1B vaccine) or a GFP-expressing phage (λ-GFP) or phosphate buffered saline (PBS) (control) and antigen-specific cell-mediated and humoral immune responses were evaluated. By day 63 post-immunization, the λ-MOMP vaccine elicited significantly higher (Pabortus. Copyright © 2013 Elsevier B.V. All rights reserved.

School nurses' attitudes and experiences regarding the human papillomavirus vaccination programme in Sweden: a population-based survey.

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Grandahl, Maria; Tydén, Tanja; Rosenblad, Andreas; Oscarsson, Marie; Nevéus, Tryggve; Stenhammar, Christina

2014-05-31

Sweden introduced a school-based human papillomavirus (HPV) vaccination programme in 2012, and school nurses are responsible for managing the vaccinations. The aim of the present study was to investigate the attitudes and experiences of school nurses regarding the school-based HPV vaccination programme 1 year after its implementation. Data were collected using a web-based questionnaire in the spring of 2013, and 83.1% (851/1024) of nurses responded. There were strong associations between the nurses' education about the HPV vaccine and their perceived knowledge about the vaccine and a favourable attitude towards vaccination (both p HPV vaccination compared with nurses with little education about HPV vaccination (adjusted odds ratio [OR] = 9.8; 95% confidence interval [CI]: 3.797-25.132). Nurses with high perceived knowledge were more likely to have a positive attitude compared with those with a low level of perceived knowledge (OR = 2.5; 95% CI: 1.299-4.955). If financial support from the government was used to fund an additional school nurse, nurses were more likely to have a positive attitude than if the financial support was not used to cover the extra expenses incurred by the HPV vaccination (OR = 2.1; 95% CI: 1.051-4.010). The majority, 648 (76.1%), had been contacted by parents with questions about the vaccine, mostly related to adverse effects. In addition, 570 (66.9%) stated that they had experienced difficulties with the vaccinations, and 337 (59.1%) of these considered the task to be time-consuming. A high level of education and perceived good knowledge about HPV are associated with a positive attitude of school nurses to the HPV vaccination programme. Thus, nurses require adequate knowledge, education, skills and time to address the questions and concerns of parents, as well as providing information about HPV. Strategic financial support is required because HPV vaccination is a complex and time-consuming task.

A history of fish vaccination: science-based disease prevention in aquaculture.

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Gudding, Roar; Van Muiswinkel, Willem B

2013-12-01

Disease prevention and control are crucial in order to maintain a sustainable aquaculture, both economically and environmentally. Prophylactic measures based on stimulation of the immune system of the fish have been an effective measure for achieving this goal. Immunoprophylaxis has become an important part in the successful development of the fish-farming industry. The first vaccine for aquaculture, a vaccine for prevention of yersiniosis in salmonid fish, was licensed in USA in 1976. Since then the use of vaccines has expanded to new countries and new species simultaneous with the growth of the aquaculture industry. This paper gives an overview of the achievements in fish vaccinology with particular emphasis on immunoprophylaxis as a practical tool for a successful development of bioproduction of aquatic animals. Copyright © 2013 Elsevier Ltd. All rights reserved.

Points for Consideration for dengue vaccine introduction - recommendations by the Dengue Vaccine Initiative.

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Lim, Jacqueline Kyungah; Lee, Yong-Seok; Wilder-Smith, Annelies; Thiry, Georges; Mahoney, Richard; Yoon, In-Kyu

2016-01-01

Dengue is a public health problem in the tropics and subtropics. There are several vaccine candidates in clinical development. However, there may be gaps in the new vaccine introduction after vaccine licensure before it becomes available in developing countries. In anticipation of the first dengue vaccine candidate to be licensed, Dengue Vaccine Initiative (DVI) and, its predecessor, Pediatric Dengue Vaccine Initiative (PDVI) have been working on points for consideration to accelerate evidence-based dengue vaccine introduction, once a vaccine becomes available. In this paper, we review the history of PDVI and its successor, the DVI, and elaborate on the points of consideration for dengue vaccine introduction.

[PERSPECTIVES OF DEVELOPMENT OF LIVE RECOMBINANT ANTHRAX VACCINES BASED ON OPPORTUNISTIC AND APATHOGENIC MICROORGANISMS].

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Popova, P Yu; Mikshis, N I

2016-01-01

Live genetic engineering anthrax vaccines on the platform of avirulent and probiotic micro-organisms are a safe and adequate alternative to preparations based on attenuated Bacillus anthracis strains. Mucosal application results in a direct contact of the vaccine preparations with mucous membranes in those organs arid tissues of the macro-organisms, that are exposed to the pathogen in the first place, resulting in a development of local and systemic immune response. Live recombinant anthrax vaccines could be used both separately as well as in a prime-boost immunization scheme. The review focuses on immunogenic and protective properties of experimental live genetic engineering prearations, created based on members of geni of Salmonella, Lactobacillus and adenoviruses.

Architectural Insight into Inovirus-Associated Vectors (IAVs and Development of IAV-Based Vaccines Inducing Humoral and Cellular Responses: Implications in HIV-1 Vaccines

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Kyriakos A. Hassapis

2014-12-01

Full Text Available Inovirus-associated vectors (IAVs are engineered, non-lytic, filamentous bacteriophages that are assembled primarily from thousands of copies of the major coat protein gp8 and just five copies of each of the four minor coat proteins gp3, gp6, gp7 and gp9. Inovirus display studies have shown that the architecture of inoviruses makes all coat proteins of the inoviral particle accessible to the outside. This particular feature of IAVs allows foreign antigenic peptides to be displayed on the outer surface of the virion fused to its coat proteins and for more than two decades has been exploited in many applications including antibody or peptide display libraries, drug design, and vaccine development against infectious and non-infectious diseases. As vaccine carriers, IAVs have been shown to elicit both a cellular and humoral response against various pathogens through the display of antibody epitopes on their coat proteins. Despite their high immunogenicity, the goal of developing an effective vaccine against HIV-1 has not yet materialized. One possible limitation of previous efforts was the use of broadly neutralizing antibodies, which exhibited autoreactivity properties. In the past five years, however, new, more potent broadly neutralizing antibodies that do not exhibit autoreactivity properties have been isolated from HIV-1 infected individuals, suggesting that vaccination strategies aimed at producing such broadly neutralizing antibodies may confer protection against infection. The utilization of these new, broadly neutralizing antibodies in combination with the architectural traits of IAVs have driven the current developments in the design of an inovirus-based vaccine against HIV-1. This article reviews the applications of IAVs in vaccine development, with particular emphasis on the design of inoviral-based vaccines against HIV-1.

Liposome-Based Adjuvants for Subunit Vaccines: Formulation Strategies for Subunit Antigens and Immunostimulators

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Signe Tandrup Schmidt

2016-03-01

Full Text Available The development of subunit vaccines has become very attractive in recent years due to their superior safety profiles as compared to traditional vaccines based on live attenuated or whole inactivated pathogens, and there is an unmet medical need for improved vaccines and vaccines against pathogens for which no effective vaccines exist. The subunit vaccine technology exploits pathogen subunits as antigens, e.g., recombinant proteins or synthetic peptides, allowing for highly specific immune responses against the pathogens. However, such antigens are usually not sufficiently immunogenic to induce protective immunity, and they are often combined with adjuvants to ensure robust immune responses. Adjuvants are capable of enhancing and/or modulating immune responses by exposing antigens to antigen-presenting cells (APCs concomitantly with conferring immune activation signals. Few adjuvant systems have been licensed for use in human vaccines, and they mainly stimulate humoral immunity. Thus, there is an unmet demand for the development of safe and efficient adjuvant systems that can also stimulate cell-mediated immunity (CMI. Adjuvants constitute a heterogeneous group of compounds, which can broadly be classified into delivery systems or immunostimulators. Liposomes are versatile delivery systems for antigens, and they can carefully be customized towards desired immune profiles by combining them with immunostimulators and optimizing their composition, physicochemical properties and antigen-loading mode. Immunostimulators represent highly diverse classes of molecules, e.g., lipids, nucleic acids, proteins and peptides, and they are ligands for pattern-recognition receptors (PRRs, which are differentially expressed on APC subsets. Different formulation strategies might thus be required for incorporation of immunostimulators and antigens, respectively, into liposomes, and the choice of immunostimulator should ideally be based on knowledge regarding the

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

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

2018-02-01

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

Design of different strategies of multivalent DNA-based vaccination against rabies and canine distemper in mice and dogs

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Touihri Leila

2012-12-01

Full Text Available Abstract Background During the vaccination campaigns, puppies younger than 3 months old are not targeted and remain unvaccinated for at least the first year of their lives. Almost half of the reported rabid dogs are 6 months or younger. Hence, we should recommend the vaccination against rabies of young puppies. Unfortunately, owing to the exposure of puppies to infections with either canine parvovirus (CPV or distemper virus (CDV after the intervention of the vaccinators, owners are reluctant to vaccinate puppies against rabies. Therefore, it is necessary to include the CPV and CDV valences in the vaccine against rabies. Multivalent DNA-based vaccination in dogs, including rabies and distemper valences, could help in raising vaccine coverage. Methods We have designed monovalent and multivalent DNA-based vaccine candidates for in vitro and in vivo assays. These plasmids encode to the rabies virus glycoprotein and/or the canine distemper virus hemagglutinin. The first strategy of multivalent DNA-based vaccination is by mixing plasmids encoding to a single antigen each. The second is by simply fusing the genes of the antigens together. The third is by adding the foot and mouth disease virus (FMDV 2A oligopeptide gene into the antigen genes. The last strategy is by the design and use of a bicistronic plasmid with an “Internal Ribosome Entry Site” (IRES domain. Results The monovalent construct against canine distemper was efficiently validated by inducing higher humoral immune responses compared to cell-culture-derived vaccine both in mice and dogs. All multivalent plasmids efficiently expressed both valences after in vitro transfection of BHK-21 cells. In BALB/c mice, the bicistronic IRES-dependant construct was the most efficient inducer of virus-neutralizing antibodies against both valences. It was able to induce better humoral immune responses compared to the administration of either cell-culture-derived vaccines or monovalent plasmids. The

Design of different strategies of multivalent DNA-based vaccination against rabies and canine distemper in mice and dogs.

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Touihri, Leila; Ahmed, Sami Belhaj; Chtourou, Yacine; Daoud, Rahma; Bahloul, Chokri

2012-12-27

During the vaccination campaigns, puppies younger than 3 months old are not targeted and remain unvaccinated for at least the first year of their lives. Almost half of the reported rabid dogs are 6 months or younger. Hence, we should recommend the vaccination against rabies of young puppies. Unfortunately, owing to the exposure of puppies to infections with either canine parvovirus (CPV) or distemper virus (CDV) after the intervention of the vaccinators, owners are reluctant to vaccinate puppies against rabies. Therefore, it is necessary to include the CPV and CDV valences in the vaccine against rabies. Multivalent DNA-based vaccination in dogs, including rabies and distemper valences, could help in raising vaccine coverage. We have designed monovalent and multivalent DNA-based vaccine candidates for in vitro and in vivo assays. These plasmids encode to the rabies virus glycoprotein and/or the canine distemper virus hemagglutinin. The first strategy of multivalent DNA-based vaccination is by mixing plasmids encoding to a single antigen each. The second is by simply fusing the genes of the antigens together. The third is by adding the foot and mouth disease virus (FMDV) 2A oligopeptide gene into the antigen genes. The last strategy is by the design and use of a bicistronic plasmid with an "Internal Ribosome Entry Site" (IRES) domain. The monovalent construct against canine distemper was efficiently validated by inducing higher humoral immune responses compared to cell-culture-derived vaccine both in mice and dogs. All multivalent plasmids efficiently expressed both valences after in vitro transfection of BHK-21 cells. In BALB/c mice, the bicistronic IRES-dependant construct was the most efficient inducer of virus-neutralizing antibodies against both valences. It was able to induce better humoral immune responses compared to the administration of either cell-culture-derived vaccines or monovalent plasmids. The FMDV 2A was also efficient in the design of multivalent

A PCV2 vaccine based on genotype 2b is more effective than a 2a-based vaccine to protect against PCV2b or combined PCV2a/2b viremia in pigs with concurrent PCV2, PRRSV and PPV infection.

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Opriessnig, Tanja; O'Neill, Kevin; Gerber, Priscilla F; de Castro, Alessandra M M G; Gimenéz-Lirola, Luis G; Beach, Nathan M; Zhou, Lei; Meng, Xiang-Jin; Wang, Chong; Halbur, Patrick G

2013-01-07

The predominant genotype of porcine circovirus (PCV) in the pig population today is PCV2b yet PCV2a-based commercial vaccines are considered effective in protecting against porcine circovirus associated disease. The objective of this study was to compare the ability of PCV2a- and PCV2b-based vaccines to control PCV2b viremia in a challenge model that mimics the U.S. field situation. Sixty-three pigs were randomly assigned to one of eight groups. Sixteen pigs were vaccinated with an experimental live-attenuated chimeric PCV1-2a vaccine based on genotype 2a and another 16 pigs with a chimeric PCV1-2b vaccine based on genotype 2b. Challenge was done 28 days post vaccination (dpv) using PCV2b (or a combination of PCV2a and PCV2b), porcine reproductive and respiratory syndrome virus (PRRSV), and porcine parvovirus (PPV) to mimic what commonly occurs in the field. The experiment was terminated 21 days post challenge (dpc) or 49dpv. Pigs vaccinated with the chimeric PCV1-2b vaccine had significantly higher levels of PCV1-2b viremia and shedding of the PCV1-2b vaccine virus in feces and nasal secretions but also a more robust humoral immune response as evidenced by significantly higher ELISA S/P ratios compared to the PCV1-2a vaccination. Regardless of challenge, the PCV1-2b vaccination significantly reduced the prevalence and amount of PCV2 viremia compared to the PCV1-2a vaccination. Interestingly, in the non-vaccinated pigs concurrent PCV2a infection resulted in clinical disease and increased macroscopic lung lesions compared to pigs challenged with PCV2b alone, further supporting the idea that concurrent PCV2a/PCV2b infection is necessary for optimal PCV2 replication. Copyright © 2012 Elsevier Ltd. All rights reserved.

Public health impact and cost effectiveness of mass vaccination with live attenuated human rotavirus vaccine (RIX4414) in India: model based analysis.

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Rose, Johnie; Hawthorn, Rachael L; Watts, Brook; Singer, Mendel E

2009-09-25

To examine the public health impact of mass vaccination with live attenuated human rotavirus vaccine (RIX4414) in a birth cohort in India, and to estimate the cost effectiveness and affordability of such a programme. Decision analytical Markov model encompassing all direct medical costs. Infection risk and severity depended on age, number of previous infections, and vaccination history; probabilities of use of inpatient and outpatient health services depended on symptom severity. Published clinical, epidemiological, and economic data. When possible, parameter estimates were based on data specific for India. Population Simulated Indian birth cohort followed for five years. Decrease in rotavirus gastroenteritis episodes (non-severe and severe), deaths, outpatient visits, and admission to hospital; incremental cost effectiveness ratio of vaccination expressed as net cost in 2007 rupees per life year saved. In the base case, vaccination prevented 28,943 (29.7%) symptomatic episodes, 6981 (38.2%) severe episodes, 164 deaths (41.0%), 7178 (33.3%) outpatient visits, and 812 (34.3%) admissions to hospital per 100,000 children. Vaccination cost 8023 rupees (about pound100, euro113, $165) per life year saved, less than India's per capita gross domestic product, a common criterion for cost effectiveness. The net programme cost would be equivalent to 11.6% of the 2006-7 budget of the Indian Department of Health and Family Welfare. Model results were most sensitive to variations in access to outpatient care for those with severe symptoms. If this parameter was increased to its upper limit, the incremental cost effectiveness ratio for vaccination still fell between one and three times the per capita gross domestic product, meeting the World Health Organization's criterion for "cost effective" interventions. Uncertainty analysis indicated a 94.7% probability that vaccination would be cost effective according to a criterion of one times per capita gross domestic product per life

Structure-Based Design of Hepatitis C Virus Vaccines That Elicit Neutralizing Antibody Responses to a Conserved Epitope

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Pierce, Brian G.; Boucher, Elisabeth N.; Piepenbrink, Kurt H.; Ejemel, Monir; Rapp, Chelsea A.; Thomas, William D.; Sundberg, Eric J.; Weng, Zhiping; Wang, Yang; Diamond, Michael S.

2017-08-09

Despite recent advances in therapeutic options, hepatitis C virus (HCV) remains a severe global disease burden, and a vaccine can substantially reduce its incidence. Due to its extremely high sequence variability, HCV can readily escape the immune response; thus, an effective vaccine must target conserved, functionally important epitopes. Using the structure of a broadly neutralizing antibody in complex with a conserved linear epitope from the HCV E2 envelope glycoprotein (residues 412 to 423; epitope I), we performed structure-based design of immunogens to induce antibody responses to this epitope. This resulted in epitope-based immunogens based on a cyclic defensin protein, as well as a bivalent immunogen with two copies of the epitope on the E2 surface. We solved the X-ray structure of a cyclic immunogen in complex with the HCV1 antibody and confirmed preservation of the epitope conformation and the HCV1 interface. Mice vaccinated with our designed immunogens produced robust antibody responses to epitope I, and their serum could neutralize HCV. Notably, the cyclic designs induced greater epitope-specific responses and neutralization than the native peptide epitope. Beyond successfully designing several novel HCV immunogens, this study demonstrates the principle that neutralizing anti-HCV antibodies can be induced by epitope-based, engineered vaccines and provides the basis for further efforts in structure-based design of HCV vaccines.

IMPORTANCEHepatitis C virus is a leading cause of liver disease and liver cancer, with approximately 3% of the world's population infected. To combat this virus, an effective vaccine would have distinct advantages over current therapeutic options, yet experimental vaccines have not been successful to date, due in part to the virus's high sequence variability leading to immune escape. In this study, we rationally designed several vaccine immunogens based on the structure of a conserved epitope that

[From new vaccine to new target: revisiting influenza vaccination].

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Gérard, M

2011-09-01

Annual vaccination is since many years the corner stone of Influenza control strategy. Because conventional vaccine are needle-based, are less immunogenic in old people and induce only systemic IgG production, intranasal and intradermal vaccines that are recently or will be soon available in Belgium will offer distinct advantages. Intradermal vaccination is on the Belgian market since 2010. A stronger immune response that allows an antigen sparing strategy is elicited because antigens are delivered near the dermal dendritic cells. Local side effects are more pronounced than after intramuscular injection. The needle-free intranasal vaccine that has been approved for use in people less than 18 years old by the EMEA in October 2010 induces also a mucosal IgA response. Improved clinical results than with intramuscular vaccine has been documented in several studies in children. Several conditions are contraindication to nasal vaccination because of patterns of side effects and because the vaccine is an live-attenuated vaccine. Pregnant women has become a top priority for Influenza vaccination in the recommendations of the High Council of Health in Belgium since the 2009 H1N1 pandemic. Several studies has since then documented the increased risk for Influenza-related morbidity in pregnant women especially during the third trimester and independently of the presence of other comorbidities. Reduced incidence of documented Influenza and of Influenza-related hospitalizations are observed in the new born of vaccinated women until 6 months of age. Availability of new vaccines for Influenza and better knowledge of the benefit of vaccination in target populations are important tools to optimize vaccine coverage of the population.

Novel Plasmodium falciparum malaria vaccines: evidence-based searching for variant surface antigens as candidates for vaccination against pregnancy-associated malaria

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Staalsoe, Trine; Jensen, Anja T R; Theander, Thor G

2002-01-01

Malaria vaccine development has traditionally concentrated on careful molecular, biochemical, and immunological characterisation of candidate antigens. In contrast, evidence of the importance of identified antigens in immunity to human infection and disease has generally been limited to statistic......Malaria vaccine development has traditionally concentrated on careful molecular, biochemical, and immunological characterisation of candidate antigens. In contrast, evidence of the importance of identified antigens in immunity to human infection and disease has generally been limited...... to statistically significant co-variation with protection rather than on demonstration of causal relationships. We have studied the relationship between variant surface antigen-specific antibodies and clinical protection from Plasmodium falciparum malaria in general, and from pregnancy-associated malaria (PAM......) in particular, to provide robust evidence of a causal link between the two in order to allow efficient and evidence-based identification of candidate antigens for malaria vaccine development....

PROTECTIVE ACTIVITY STUDY OF A CANDIDATE VACCINE AGAINST ROTAVIRUS INFECTION BASED ON RECOMBINANT PROTEIN FliCVP6VP8

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I. V. Dukhovlinov

2016-01-01

Full Text Available Rotavirus infection is among leading causes of severe diarrhea which often leads to severe dehydration, especially, in children under 5 years old. In Russia, the incidence of rotavirus infection is constantly increased, due to higher rates of actual rotavirus infection cases and improved diagnostics of the disease. Immunity to rotavirus is unstable, thus causing repeated infections intra vitam. Anti-infectious resistance in reconvalescents is explained by induction of specific IgM, IgG, and, notably, IgA antibodies. Due to absence of market drugs with direct action against rotavirus, a rational vaccination is considered the most effective way to control the disease. Currently available vaccines for prevention of rotavirus infection are based on live attenuated rotavirus strains, human and/or animal origin, which replicate in human gut. Their implementation may result into different complications. Meanwhile, usage of vaccines based on recombinant proteins is aimed to avoid risks associated with introduction of a complete virus into humans. In this paper, we studied protective activity of candidate vaccines against rotavirus.In this work we studied protective activity of a candidate vaccine against rotavirus infection based on recombinant FliCVP6VP8 protein which includes VP6 and VP8, as well as components of Salmonella typhimurium flagellin (FliC as an adjuvant. Different components are joined by flexible bridges. Efficiency of the candidate vaccine was studied in animal model using Balb/c mice. We have shown high level of protection which occurs when the candidate vaccine is administered twice intramuscularly. Complete protection of animals against mouse rotavirus EDC after intramuscular immunization with a candidate vaccine was associated with arising rotavirus-specific IgA and IgG antibodies in serum and intestine of immunized animals. The efficacy of candidate vaccine based on recombinant protein FliCVP6VP8 against rotavirus infection was

Bacterially produced recombinant influenza vaccines based on virus-like particles.

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Andrea Jegerlehner

Full Text Available Although current influenza vaccines are effective in general, there is an urgent need for the development of new technologies to improve vaccine production timelines, capacities and immunogenicity. Herein, we describe the development of an influenza vaccine technology which enables recombinant production of highly efficient influenza vaccines in bacterial expression systems. The globular head domain of influenza hemagglutinin, comprising most of the protein's neutralizing epitopes, was expressed in E. coli and covalently conjugated to bacteriophage-derived virus-like particles produced independently in E.coli. Conjugate influenza vaccines produced this way were used to immunize mice and found to elicit immune sera with high antibody titers specific for the native influenza hemagglutinin protein and high hemagglutination-inhibition titers. Moreover vaccination with these vaccines induced full protection against lethal challenges with homologous and highly drifted influenza strains.

Shikonin enhances efficacy of a gene-based cancer vaccine via induction of RANTES

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Chen Hui-Ming

2012-04-01

Full Text Available Abstract Background Shikonin, a phytochemical purified from Lithospermum erythrorhizon, has been shown to confer diverse pharmacological activities, including accelerating granuloma formation, wound healing, anti-inflammation and others, and is explored for immune-modifier activities for vaccination in this study. Transdermal gene-based vaccine is an attractive approach for delivery of DNA transgenes encoding specific tumor antigens to host skin tissues. Skin dendritic cells (DCs, a potent antigen-presenting cell type, is known to play a critical role in transmitting and orchestrating tumor antigen-specific immunities against cancers. The present study hence employs these various components for experimentation. Method The mRNA and protein expression of RANTES were detected by RT-PCR and ELISA, respectively. The regional expression of RANTES and tissue damage in test skin were evaluated via immunohistochemistry assay. Fluorescein isothiocyanate sensitization assay was performed to trace the trafficking of DCs from the skin vaccination site to draining lymph nodes. Adjuvantic effect of shikonin on gene gun-delivered human gp100 (hgp100 DNA cancer vaccine was studied in a human gp100-transfected B16 (B16/hgp100 tumor model. Results Among various phytochemicals tested, shikonin induced the highest level of expression of RANTES in normal skin tissues. In comparison, mouse RANTES cDNA gene transfection induced a higher level of mRANTES expression for a longer period, but caused more extensive skin damage. Topical application of shikonin onto the immunization site before gene gun-mediated vaccination augmented the population of skin DCs migrating into the draining lymph nodes. A hgp100 cDNA gene vaccination regimen with shikonin pretreatment as an adjuvant in a B16/hgp100 tumor model increased cytotoxic T lymphocyte activities in splenocytes and lymph node cells on target tumor cells. Conclusion Together, our findings suggest that shikonin can

Oral Immunization with a Multivalent Epitope-Based Vaccine, Based on NAP, Urease, HSP60, and HpaA, Provides Therapeutic Effect on H. pylori Infection in Mongolian gerbils.

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Guo, Le; Yang, Hua; Tang, Feng; Yin, Runting; Liu, Hongpeng; Gong, Xiaojuan; Wei, Jun; Zhang, Ying; Xu, Guangxian; Liu, Kunmei

2017-01-01

Epitope-based vaccine is a promising strategy for therapeutic vaccination against Helicobacter pylori ( H. pylori ) infection. A multivalent subunit vaccine containing various antigens from H. pylori is superior to a univalent subunit vaccine. However, whether a multivalent epitope-based vaccine is superior to a univalent epitope-based vaccine in therapeutic vaccination against H. pylori , remains unclear. In this study, a multivalent epitope-based vaccine named CWAE against H. pylori urease, neutrophil-activating protein (NAP), heat shock protein 60 (HSP60) and H. pylori adhesin A (HpaA) was constructed based on mucosal adjuvant cholera toxin B subunit (CTB), Th1-type adjuvant NAP, multiple copies of selected B and Th cell epitopes (UreA 27-53 , UreA 183-203 , HpaA 132-141 , and HSP60 189-203 ), and also the epitope-rich regions of urease B subunit (UreB 158-251 and UreB 321-385 ) predicted by bioinformatics. Immunological properties of CWAE vaccine were characterized in BALB/c mice model. Its therapeutic effect was evaluated in H. pylori -infected Mongolian gerbil model by comparing with a univalent epitope-based vaccine CTB-UE against H. pylori urease that was constructed in our previous studies. Both CWAE and CTB-UE could induce similar levels of specific antibodies against H. pylori urease, and had similar inhibition effect of H. pylori urease activity. However, only CWAE could induce high levels of specific antibodies to NAP, HSP60, HpaA, and also the synthetic peptides epitopes (UreB 158-172 , UreB 181-195 , UreB 211-225 , UreB 349-363 , HpaA 132-141 , and HSP60 189-203 ). In addition, oral therapeutic immunization with CWAE significantly reduced the number of H. pylori colonies in the stomach of Mongolian gerbils, compared with oral immunization using CTB-UE or H. pylori urease. The protection of CWAE was associated with higher levels of mixed CD4 + T cell (Th cell) response, IgG, and secretory IgA (sIgA) antibodies to H. pylori . These results indic ate

Oral Immunization with a Multivalent Epitope-Based Vaccine, Based on NAP, Urease, HSP60, and HpaA, Provides Therapeutic Effect on H. pylori Infection in Mongolian gerbils

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Le Guo

2017-08-01

Full Text Available Epitope-based vaccine is a promising strategy for therapeutic vaccination against Helicobacter pylori (H. pylori infection. A multivalent subunit vaccine containing various antigens from H. pylori is superior to a univalent subunit vaccine. However, whether a multivalent epitope-based vaccine is superior to a univalent epitope-based vaccine in therapeutic vaccination against H. pylori, remains unclear. In this study, a multivalent epitope-based vaccine named CWAE against H. pylori urease, neutrophil-activating protein (NAP, heat shock protein 60 (HSP60 and H. pylori adhesin A (HpaA was constructed based on mucosal adjuvant cholera toxin B subunit (CTB, Th1-type adjuvant NAP, multiple copies of selected B and Th cell epitopes (UreA27–53, UreA183–203, HpaA132–141, and HSP60189–203, and also the epitope-rich regions of urease B subunit (UreB158–251 and UreB321–385 predicted by bioinformatics. Immunological properties of CWAE vaccine were characterized in BALB/c mice model. Its therapeutic effect was evaluated in H. pylori-infected Mongolian gerbil model by comparing with a univalent epitope-based vaccine CTB-UE against H. pylori urease that was constructed in our previous studies. Both CWAE and CTB-UE could induce similar levels of specific antibodies against H. pylori urease, and had similar inhibition effect of H. pylori urease activity. However, only CWAE could induce high levels of specific antibodies to NAP, HSP60, HpaA, and also the synthetic peptides epitopes (UreB158–172, UreB181–195, UreB211–225, UreB349–363, HpaA132–141, and HSP60189–203. In addition, oral therapeutic immunization with CWAE significantly reduced the number of H. pylori colonies in the stomach of Mongolian gerbils, compared with oral immunization using CTB-UE or H. pylori urease. The protection of CWAE was associated with higher levels of mixed CD4+ T cell (Th cell response, IgG, and secretory IgA (sIgA antibodies to H. pylori. These results indic

Phylogeny and History of the Lost SIV from Crab-Eating Macaques: SIVmfa.

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Kevin R McCarthy

Full Text Available In the 20th century, thirteen distinct human immunodeficiency viruses emerged following independent cross-species transmission events involving simian immunodeficiency viruses (SIV from African primates. In the late 1900s, pathogenic SIV strains also emerged in the United Sates among captive Asian macaque species following their unintentional infection with SIV from African sooty mangabeys (SIVsmm. Since their discovery in the 1980s, SIVs from rhesus macaques (SIVmac and pig-tailed macaques (SIVmne have become invaluable models for studying HIV pathogenesis, vaccine design and the emergence of viruses. SIV isolates from captive crab-eating macaques (SIVmfa were initially described but lost prior to any detailed molecular and genetic characterization. In order to infer the origins of the lost SIVmfa lineage, we located archived material and colony records, recovered its genomic sequence by PCR, and assessed its phylogenetic relationship to other SIV strains. We conclude that SIVmfa is the product of two cross-species transmission events. The first was the established transmission of SIVsmm to rhesus macaques, which occurred at the California National Primate Research Center in the late 1960s and the virus later emerged as SIVmac. In a second event, SIVmac was transmitted to crab-eating macaques, likely at the Laboratory for Experimental Medicine and Surgery in Primates in the early 1970s, and it was later spread to the New England Primate Research Center colony in 1973 and eventually isolated in 1986. Our analysis suggests that SIVmac had already emerged by the early 1970s and had begun to diverge into distinct lineages. Furthermore, our findings suggest that pathogenic SIV strains may have been more widely distributed than previously appreciated, raising the possibility that additional isolates may await discovery.

Phylogeny and History of the Lost SIV from Crab-Eating Macaques: SIVmfa.

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McCarthy, Kevin R; Johnson, Welkin E; Kirmaier, Andrea

2016-01-01

In the 20th century, thirteen distinct human immunodeficiency viruses emerged following independent cross-species transmission events involving simian immunodeficiency viruses (SIV) from African primates. In the late 1900s, pathogenic SIV strains also emerged in the United Sates among captive Asian macaque species following their unintentional infection with SIV from African sooty mangabeys (SIVsmm). Since their discovery in the 1980s, SIVs from rhesus macaques (SIVmac) and pig-tailed macaques (SIVmne) have become invaluable models for studying HIV pathogenesis, vaccine design and the emergence of viruses. SIV isolates from captive crab-eating macaques (SIVmfa) were initially described but lost prior to any detailed molecular and genetic characterization. In order to infer the origins of the lost SIVmfa lineage, we located archived material and colony records, recovered its genomic sequence by PCR, and assessed its phylogenetic relationship to other SIV strains. We conclude that SIVmfa is the product of two cross-species transmission events. The first was the established transmission of SIVsmm to rhesus macaques, which occurred at the California National Primate Research Center in the late 1960s and the virus later emerged as SIVmac. In a second event, SIVmac was transmitted to crab-eating macaques, likely at the Laboratory for Experimental Medicine and Surgery in Primates in the early 1970s, and it was later spread to the New England Primate Research Center colony in 1973 and eventually isolated in 1986. Our analysis suggests that SIVmac had already emerged by the early 1970s and had begun to diverge into distinct lineages. Furthermore, our findings suggest that pathogenic SIV strains may have been more widely distributed than previously appreciated, raising the possibility that additional isolates may await discovery.

What Vaccines Do You Need?

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... Recommendations Why Immunize? Vaccines: The Basics The Adult Vaccine Quiz Language: English Español (Spanish) Recommend on Facebook Tweet Share Compartir Vaccines are recommended for adults based on age, health ...

A chimeric measles virus with a lentiviral envelope replicates exclusively in CD4+/CCR5+ cells

International Nuclear Information System (INIS)

Mourez, Thomas; Mesel-Lemoine, Mariana; Combredet, Chantal; Najburg, Valerie; Cayet, Nadege; Tangy, Frederic

2011-01-01

We generated a replicating chimeric measles virus in which the hemagglutinin and fusion surface glycoproteins were replaced with the gp160 envelope glycoprotein of simian immunodeficiency virus (SIVmac239). Based on a previously cloned live-attenuated Schwarz vaccine strain of measles virus (MV), this chimera was rescued at high titers using reverse genetics in CD4+ target cells. Cytopathic effect consisted in the presence of large cell aggregates evolving to form syncytia, as observed during SIV infection. The morphology of the chimeric virus was identical to that of the parent MV particles. The presence of SIV gp160 as the only envelope protein on chimeric particles surface altered the cell tropism of the new virus from CD46+ to CD4+ cells. Used as an HIV candidate vaccine, this MV/SIVenv chimeric virus would mimic transient HIV-like infection, benefiting both from HIV-like tropism and the capacity of MV to replicate in dendritic cells, macrophages and lymphocytes.

Entirely Carbohydrate-Based Vaccines: An Emerging Field for Specific and Selective Immune Responses

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Sharmeen Nishat

2016-05-01

Full Text Available Carbohydrates are regarded as promising targets for vaccine development against infectious disease because cell surface glycans on many infectious agents are attributed to playing an important role in pathogenesis. In addition, oncogenic transformation of normal cells, in many cases, is associated with aberrant glycosylation of the cell surface glycan generating tumor associated carbohydrate antigens (TACAs. Technological advances in glycobiology have added a new dimension to immunotherapy when considering carbohydrates as key targets in developing safe and effective vaccines to combat cancer, bacterial infections, viral infections, etc. Many consider effective vaccines induce T-cell dependent immunity with satisfactory levels of immunological memory that preclude recurrence. Unfortunately, carbohydrates alone are poorly immunogenic as they do not bind strongly to the MHCII complex and thus fail to elicit T-cell immunity. To increase immunogenicity, carbohydrates have been conjugated to carrier proteins, which sometimes can impede carbohydrate specific immunity as peptide-based immune responses can negate antibodies directed at the targeted carbohydrate antigens. To overcome many challenges in using carbohydrate-based vaccine design and development approaches targeting cancer and other diseases, zwitterionic polysaccharides (ZPSs, isolated from the capsule of commensal anaerobic bacteria, will be discussed as promising carriers of carbohydrate antigens to achieve desired immunological responses.

Midwives' influenza vaccine uptake and their views on vaccination of pregnant women.

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Ishola, D A; Permalloo, N; Cordery, R J; Anderson, S R

2013-12-01

Pregnant women in England are now offered seasonal influenza vaccine. Midwives could be influential in promoting this, but specific information on their views on the policy and their role in its implementation is lacking. London midwives were surveyed for their views on the new policy and their own vaccine uptake, using an anonymously self-completed semi-structured online survey via a convenience sampling approach. In total, 266 midwives responded. Sixty-nine percent agreed with the policy of vaccinating all pregnant women. Seventy-six percent agreed that midwives should routinely advise pregnant women on vaccination, but only 25% felt adequately prepared for this role. Just 28% wished to be vaccinators, due to concerns about increased workload and inadequate training. Forty-three percent received seasonal influenza vaccine themselves. Major reasons for non-uptake were doubts about vaccine necessity (34%), safety (25%) and effectiveness (10%); and poor arrangements for vaccination (11%). Suggested strategies for improving their own uptake included better access to evidence of effectiveness (67%) and improved work-based vaccination (45%). London midwives support influenza vaccination of pregnant women, but are more willing to give advice on, than to administer, the vaccine. Midwives' own influenza vaccine uptake could improve with more information and easier access to vaccination in their workplace.

Effect of School-based Human Papillomavirus (HPV) Vaccination on ...

African Journals Online (AJOL)

... de comportement des pairs positifs. Des obstacles majeurs à l'acceptation du vaccin ont été: les rumeurs et les idées fausses au sujet des effets secondaires possibles, information inadéquate perçue sur le vaccin, et la peur des effets secondaires. Mots clés: adolescentes; connaissances; acceptabilité; vaccin; Ouganda ...

Print News Coverage of School-Based HPV Vaccine Mandate

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Casciotti, Dana; Smith, Katherine C.; Andon, Lindsay; Vernick, Jon; Tsui, Amy; Klassen, Ann C.

2015-01-01

BACKGROUND In 2007, legislation was proposed in 24 states and the District of Columbia for school-based HPV vaccine mandates, and mandates were enacted in Texas, Virginia, and the District of Columbia. Media coverage of these events was extensive, and media messages both reflected and contributed to controversy surrounding these legislative activities. Messages communicated through the media are an important influence on adolescent and parent understanding of school-based vaccine mandates. METHODS We conducted structured text analysis of newspaper coverage, including quantitative analysis of 169 articles published in mandate jurisdictions from 2005-2009, and qualitative analysis of 63 articles from 2007. Our structured analysis identified topics, key stakeholders and sources, tone, and the presence of conflict. Qualitative thematic analysis identified key messages and issues. RESULTS Media coverage was often incomplete, providing little context about cervical cancer or screening. Skepticism and autonomy concerns were common. Messages reflected conflict and distrust of government activities, which could negatively impact this and other youth-focused public health initiatives. CONCLUSIONS If school health professionals are aware of the potential issues raised in media coverage of school-based health mandates, they will be more able to convey appropriate health education messages, and promote informed decision-making by parents and students. PMID:25099421

Adenovirus-based vaccine against Listeria monocytogenes

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Jensen, Søren; Steffensen, Maria Abildgaard; Jensen, Benjamin Anderschou Holbech

2013-01-01

The use of replication-deficient adenoviruses as vehicles for transfer of foreign genes offers many advantages in a vaccine setting, eliciting strong cellular immune responses involving both CD8(+) and CD4(+) T cells. Further improving the immunogenicity, tethering of the inserted target Ag to MHC...... linked to Ii compared with vaccination with the unlinked vaccine. Studies using knockout mice demonstrated that CD8(+) T cells were largely responsible for this protection, which is mediated through perforin-dependent lysis of infected cells and IFN-γ production. Taking the concept a step further...

Monitoring vaccine and non-vaccine HPV type prevalence in the post-vaccination era in women living in the Basilicata region, Italy.

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Carozzi, Francesca; Puliti, Donella; Ocello, Cristina; Anastasio, Pasquale Silvio; Moliterni, Espedito Antonio; Perinetti, Emilia; Serradell, Laurence; Burroni, Elena; Confortini, Massimo; Mantellini, Paola; Zappa, Marco; Dominiak-Felden, Géraldine

2018-01-15

A large free-of-charge quadrivalent HPV (qHPV) vaccination program, covering four cohorts annually (women 11, 14, 17 and 24 years), has been implemented in Basilicata since 2007. This study evaluated vaccine and non-vaccine HPV prevalence 5-7 years post-vaccination program implementation in vaccinated and unvaccinated women. This population-based, cross-sectional study was conducted in the public screening centers of the Local Health Unit in Matera between 2012 and 2014. Cervical samples were obtained for Pap and HPV testing (HC2, LiPA Extra® assay) and participants completed a sociodemographic and behavioral questionnaire. Detailed HPV vaccination status was retrieved from the official HPV vaccine registry. HPV prevalence was described overall, by type and vaccination status. The association between HPV type-detection and risk/protective factors was studied. Direct vaccine protection (qHPV vaccine effectiveness [VE]), cross-protection, and type-replacement were evaluated in cohorts eligible for vaccination, by analyzing HPV prevalence of vaccine and non-vaccine types according to vaccination status. Overall, 2793 women (18-50 years) were included, 1314 of them having been in birth cohorts eligible for the HPV vaccination program (18- to 30-year-old women at enrolment). Among the latter, qHPV vaccine uptake was 59% (at least one dose), with 94% completing the schedule; standardized qHPV type prevalence was 0.6% in vaccinated versus 5.5% in unvaccinated women (P HPV, high-risk non-vaccine HPV, or any single non-vaccine type prevalence was observed between vaccinated and unvaccinated women. These results, conducted in a post-vaccine era, suggest a high qHPV VE and that a well-implemented catch-up vaccination program may be efficient in reducing vaccine-type infections in a real-world setting. No cross-protective effect or evidence of type-replacement was observed a few years after HPV vaccine introduction.

Current Ebola vaccines

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Hoenen, Thomas; Groseth, Allison; Feldmann, Heinz

2012-01-01

Introduction Ebolaviruses cause severe viral hemorrhagic fever in humans and non-human primates, with case fatality rates of up to 90%. Currently, neither a specific treatment nor a vaccine licensed for use in humans is available. However, a number of vaccine candidates have been developed in the last decade that are highly protective in non-human primates, the gold standard animal model for Ebola hemorrhagic fever. Areas covered This review analyzes a number of scenarios for the use of ebolavirus vaccines, discusses the requirements for ebolavirus vaccines in these scenarios, and describes current ebolavirus vaccines. Among these vaccines are recombinant Adenoviruses, recombinant Vesicular Stomatitis viruses, recombinant Human Parainfluenza viruses and virus-like particles. Interestingly, one of these vaccine platforms, based on recombinant Vesicular Stomatitis viruses, has also demonstrated post-exposure protection in non-human primates. Expert opinion The most pressing remaining challenge is now to move these vaccine candidates forward into human trials and towards licensure. In order to achieve this, it will be necessary to establish the mechanisms and correlates of protection for these vaccines, and to continue to demonstrate their safety, particularly in potentially immunocompromised populations. However, already now there is sufficient evidence that, from a scientific perspective, a vaccine protective against ebolaviruses is possible. PMID:22559078

Efficacy, Safety, and Interactions of a Live Infectious Bursal Disease Virus Vaccine for Chickens Based on Strain IBD V877.

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Geerligs, Harm J; Ons, Ellen; Boelm, Gert Jan; Vancraeynest, Dieter

2015-03-01

Infectious bursal disease (IBD) is a highly contagious disease in young chickens which can result in high morbidity and mortality and also in great economic losses. The main target for the virus is the lymphoid tissue with a special predilection for the bursa of Fabricius. Several vaccines are available to control the disease. Intermediate plus vaccines are used in chickens with high maternal antibody titers which face high infection pressure. An example of an intermediate plus vaccine is a live vaccine based on IBD strain V877. The results of an efficacy study in commercial broilers with different levels of maternally derived antibodies (MDA) showed that the V877-based IBD vaccine can break through maternal antibody titers of higher than 1100 as determined by an IBD ELISA. The safety of the vaccine was demonstrated in a study in which specific-pathogen-free (SPF) chickens were vaccinated with a tenfold dose of the vaccine strain and a tenfold dose of the vaccine strain after five back passages in SPF chickens. The vaccine virus caused lesions, as could be expected for an intermediate plus vaccine, but the scores were not much higher than the maximal scores allowed for mild IBD vaccines in the European Pharmacopoeia, and reversion to virulence was absent. In studies in SPF chickens, there were no negative impacts by the IBD V877 vaccine on the efficacy of a live QX-like IB vaccine and a live Newcastle disease La Sota vaccine in vaccination challenge studies, although the IBD vaccine had a negative effect on the antibody response generated by the QX-like IB vaccine. It is concluded that the IBD V877 vaccine has the capacity to break through high levels of MDA, has a satisfactory safety profile, and interactions with other live vaccines are limited. In order to limit bursal lesions after vaccination it is recommended to confirm the presence of MDA before vaccinating with the V877 vaccine.

Vaccination: problems and perspectives.

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S. M. Kharit

2009-01-01

Full Text Available Massive vaccination had proved its effective morbidity reduction. Today it is necessary to extend vaccination schedule, creation of selective, regional schedules based on epidemiological, clinical, economical substantiation. Development of vaccination needs the profound scientific research, modernization of adverse reaction observing system, betterment training system and awareness of population.

PERSPECTIVES OF THE DEVELOPMENT OF MUCOSAL VACCINES AGAINST DANGEROUS INFECTIONS ON THE BASE OF TRANSGENIC PLANTS

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A.V. Tretyakova

2012-08-01

Full Text Available Mucosal vaccines created on the base of transgenic plants reacting with mucosal layers of the intestines and other organs are considered to be the perspective method of the vaccination. These vaccines induce both mucosal and general humoral immunogenicity after the peroral administration. The folding of antigenic proteins synthesizing in plants occurs via eukaryotic type and has advantages before yeast and prokaryotic platforms. This feature results to more adequate synthesis of antibodies against pathogens and to the interaction with effector molecules of complement. Earlier we together with The State Scientific Center “Vector”, Institute of chemical biology and fundamental medicine SB RAS and Dr R.Hammond from Laboratory of Plant Pathology (Maryland, USA created two candidate vaccines : one of them against AIDS (HIV-1 and hepatitis B on the base of the chimeric gene TBI-HBS, encoding simultaneously 9 antigenic determinants of HIV-1 and the main surface antigen of hepatitis B (HBsAg. The second candidate vaccine was created against hepatitis B on the base of the genetic construct with the gene preS2-S encoding the synthesis of two subunits of the main surface antigen of hepatitis B and the signal peptide HDEL which directed antigens for the accumulation on ER. Both vaccines were tested on mice and confirmed their immunogenicity as the pronounced antibodies response. Twice vaccinated mice maintained the antibodies response during 11 months after there was little tendency to lowering. It was established that transgenic plants – vaccines (tomato kept the capability to the synthesis of antigenic determinants in seven seed generations during 7 years. The results of the development of the mucosal vaccine against cervical carcinoma (carcinoma of uterine cervix evoked by human papillomaviruses of high oncogenic risks were presented in this report. We created the genetic construct consisting of 35S CaMV promoter, Ώ (omega leader of TMV, the

[Mumps vaccine virus transmission].

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Otrashevskaia, E V; Kulak, M V; Otrashevskaia, A V; Karpov, I A; Fisenko, E G; Ignat'ev, G M

2013-01-01

In this work we report the mumps vaccine virus shedding based on the laboratory confirmed cases of the mumps virus (MuV) infection. The likely epidemiological sources of the transmitted mumps virus were children who were recently vaccinated with the mumps vaccine containing Leningrad-Zagreb or Leningrad-3 MuV. The etiology of the described cases of the horizontal transmission of both mumps vaccine viruses was confirmed by PCR with the sequential restriction analysis.

Cost Effectiveness of Influenza Vaccine for U.S. Children: Live Attenuated and Inactivated Influenza Vaccine.

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Shim, Eunha; Brown, Shawn T; DePasse, Jay; Nowalk, Mary Patricia; Raviotta, Jonathan M; Smith, Kenneth J; Zimmerman, Richard K

2016-09-01

Prior studies showed that live attenuated influenza vaccine (LAIV) is more effective than inactivated influenza vaccine (IIV) in children aged 2-8 years, supporting the Centers for Disease Control and Prevention (CDC) recommendations in 2014 for preferential LAIV use in this age group. However, 2014-2015 U.S. effectiveness data indicated relatively poor effectiveness of both vaccines, leading CDC in 2015 to no longer prefer LAIV. An age-structured model of influenza transmission and vaccination was developed, which incorporated both direct and indirect protection induced by vaccination. Based on this model, the cost effectiveness of influenza vaccination strategies in children aged 2-8 years in the U.S. was estimated. The base case assumed a mixed vaccination strategy where 33.3% and 66.7% of vaccinated children aged 2-8 years receive LAIV and IIV, respectively. Analyses were performed in 2014-2015. Using published meta-analysis vaccine effectiveness data (83% LAIV and 64% IIV), exclusive LAIV use would be a cost-effective strategy when vaccinating children aged 2-8 years, whereas IIV would not be preferred. However, when 2014-2015 U.S. effectiveness data (0% LAIV and 15% IIV) were used, IIV was likely to be preferred. The cost effectiveness of influenza vaccination in children aged 2-8 years is highly dependent on vaccine effectiveness; the vaccine type with higher effectiveness is preferred. In general, exclusive IIV use is preferred over LAIV use, as long as vaccine effectiveness is higher for IIV than for LAIV. Copyright © 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Microneedle-based drug and vaccine delivery via nanoporous microneedle arrays

OpenAIRE

Maaden, van der, Koen; Lüttge, R Regina; Vos, PJW; Bouwstra, Joke A; Kersten, Gideon FA; Ploemen, IHJ Ingmar

2015-01-01

In the literature, several types of microneedles have been extensively described. However, porous microneedle arrays only received minimal attention. Hence, only little is known about drug delivery via these microneedles. However, porous microneedle arrays may have potential for future microneedle-based drug and vaccine delivery and could be a valuable addition to the other microneedle-based drug delivery approaches. To gain more insight into porous microneedle technologies, the scientific an...

Ebolavirus Vaccines: Progress in the Fight Against Ebola Virus Disease

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Xiao-Xin Wu

2015-11-01

Full Text Available Ebolaviruses are highly infectious pathogens that cause lethal Ebola virus disease (EVD in humans and non-human primates (NHPs. Due to their high pathogenicity and transmissibility, as well as the potential to be misused as a bioterrorism agent, ebolaviruses would threaten the health of global populations if not controlled. In this review, we describe the origin and structure of ebolaviruses and the development of vaccines from the beginning of the 1980s, including conventional ebolavirus vaccines, DNA vaccines, Ebola virus-like particles (VLPs, vaccinia virus-based vaccines, Venezuelan equine encephalitis virus (VEEV-like replicon particles, Kunjin virus-based vaccine, recombinant Zaire Ebolavirus∆VP30, recombinant cytomegalovirus (CMV-based vaccines, recombinant rabies virus (RABV-based vaccines, recombinant paramyxovirus-based vaccines, adenovirus-based vaccines and vesicular stomatitis virus (VSV-based vaccines. No licensed vaccine or specific treatment is currently available to counteract ebolavirus infection, although DNA plasmids and several viral vector approaches have been evaluated as promising vaccine platforms. These vaccine candidates have been confirmed to be successful in protecting NHPs against lethal infection. Moreover, these vaccine candidates were successfully advanced to clinical trials. The present review provides an update of the current research on Ebola vaccines, with the aim of providing an overview on current prospects in the fight against EVD.

Theory-Based Analysis of Interest in an HIV Vaccine for Reasons Indicative of Risk Compensation Among African American Women.

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Painter, Julia E; Temple, Brandie S; Woods, Laura A; Cwiak, Carrie; Haddad, Lisa B; Mulligan, Mark J; DiClemente, Ralph J

2018-06-01

Licensure of an HIV vaccine could reduce or eliminate HIV among vulnerable populations. However, vaccine effectiveness could be undermined by risk compensation (RC), defined by an increase in risky behavior due to a belief that the vaccine will confer protection. Interest in an HIV vaccine for reasons indicative of RC may serve as an indicator of actual RC in a postlicensure era. This study assessed factors associated with interest in an HIV vaccine for reasons indicative of RC among African American women aged 18 to 55 years, recruited from a hospital-based family planning clinic in Atlanta, Georgia ( N = 321). Data were collected using audio-computer-assisted surveys. Survey items were guided by risk homeostasis theory and social cognitive theory. Multivariable logistic regression was used to assess determinants of interest in an HIV vaccine for reasons indicative of RC. Thirty-eight percent of the sample expressed interest in an HIV vaccine for at least one reason indicative of RC. In the final model, interest in an HIV vaccine for reasons indicative of RC was positively associated with higher impulsivity, perceived benefits of sexual risk behaviors, and perceived benefits of HIV vaccination; it was negatively associated with having at least some college education, positive future orientation, and self-efficacy for sex refusal. Results suggest that demographic, personality, and theory-based psychosocial factors are salient to wanting an HIV vaccine for reasons indicative of RC, and underscore the need for risk-reduction counseling alongside vaccination during the eventual rollout of an HIV vaccine.

Interference of an ERM-vaccine with a VHS-DNA vaccine in rainbow trout

DEFF Research Database (Denmark)

Lorenzen, Ellen; Einer-Jensen, Katja; Rasmussen, Jesper Skou

Simultaneous vaccination of fish against several diseases is often desirable in order to minimise cost and handling of the fish. Intramuscular DNA-vaccination of rainbow trout against viral haemorrhagic septicaemia virus (VHSV) has proved to provide very good protection. However, preliminary...... results showed that intraperitoneal injection of a commercial vaccine against Enteric Redmouth Disease (ERM) based on formalin-killed bacteria in oil adjuvant immediately followed by intramuscular injection of an experimental DNA-vaccine against VHSV, decreased the protective effect of the DNA......-vaccine against challenge with VHSV 11 weeks post vaccination (pv). This experiment was performed with rainbow trout of 30 g injected with 0.5 g VHS-DNA vaccine. The experiment was later repeated with smaller fish (2.5g) and using two different doses of DNA-vaccine, 1 g and 0.05 g. Both doses provided good...

Vaccination persuasion online: a qualitative study of two provaccine and two vaccine-skeptical websites.

Science.gov (United States)

Grant, Lenny; Hausman, Bernice L; Cashion, Margaret; Lucchesi, Nicholas; Patel, Kelsey; Roberts, Jonathan

2015-05-29

Current concerns about vaccination resistance often cite the Internet as a source of vaccine controversy. Most academic studies of vaccine resistance online use quantitative methods to describe misinformation on vaccine-skeptical websites. Findings from these studies are useful for categorizing the generic features of these websites, but they do not provide insights into why these websites successfully persuade their viewers. To date, there have been few attempts to understand, qualitatively, the persuasive features of provaccine or vaccine-skeptical websites. The purpose of this research was to examine the persuasive features of provaccine and vaccine-skeptical websites. The qualitative analysis was conducted to generate hypotheses concerning what features of these websites are persuasive to people seeking information about vaccination and vaccine-related practices. This study employed a fully qualitative case study methodology that used the anthropological method of thick description to detail and carefully review the rhetorical features of 1 provaccine government website, 1 provaccine hospital website, 1 vaccine-skeptical information website focused on general vaccine safety, and 1 vaccine-skeptical website focused on a specific vaccine. The data gathered were organized into 5 domains: website ownership, visual and textual content, user experience, hyperlinking, and social interactivity. The study found that the 2 provaccine websites analyzed functioned as encyclopedias of vaccine information. Both of the websites had relatively small digital ecologies because they only linked to government websites or websites that endorsed vaccination and evidence-based medicine. Neither of these websites offered visitors interactive features or made extensive use of the affordances of Web 2.0. The study also found that the 2 vaccine-skeptical websites had larger digital ecologies because they linked to a variety of vaccine-related websites, including government websites. They

Local measles vaccination gaps in Germany and the role of vaccination providers.

Science.gov (United States)

Eichner, Linda; Wjst, Stephanie; Brockmann, Stefan O; Wolfers, Kerstin; Eichner, Martin

2017-08-14

Measles elimination in Europe is an urgent public health goal, yet despite the efforts of its member states, vaccination gaps and outbreaks occur. This study explores local vaccination heterogeneity in kindergartens and municipalities of a German county. Data on children from mandatory school enrolment examinations in 2014/15 in Reutlingen county were used. Children with unknown vaccination status were either removed from the analysis (best case) or assumed to be unvaccinated (worst case). Vaccination data were translated into expected outbreak probabilities. Physicians and kindergartens with statistically outstanding numbers of under-vaccinated children were identified. A total of 170 (7.1%) of 2388 children did not provide a vaccination certificate; 88.3% (worst case) or 95.1% (best case) were vaccinated at least once against measles. Based on the worst case vaccination coverage, measles introduction lies between 39.5% (best case) and 73.0% (worst case). Four paediatricians were identified who accounted for 41 of 109 unvaccinated children and for 47 of 138 incomplete vaccinations; GPs showed significantly higher rates of missing vaccination certificates and unvaccinated or under-vaccinated children than paediatricians. Missing vaccination certificates pose a severe problem regarding the interpretability of vaccination data. Although the coverage for at least one measles vaccination is higher in the studied county than in most South German counties and higher than the European average, many severe and potentially dangerous vaccination gaps occur locally. If other federal German states and EU countries show similar vaccination variability, measles elimination may not succeed in Europe.

Mechanism of action of mRNA-based vaccines.

Science.gov (United States)

Iavarone, Carlo; O'hagan, Derek T; Yu, Dong; Delahaye, Nicolas F; Ulmer, Jeffrey B

2017-09-01

The present review summarizes the growing body of work defining the mechanisms of action of this exciting new vaccine technology that should allow rational approaches in the design of next generation mRNA vaccines. Areas covered: Bio-distribution of mRNA, localization of antigen production, role of the innate immunity, priming of the adaptive immune response, route of administration and effects of mRNA delivery systems. Expert commentary: In the last few years, the development of RNA vaccines had a fast growth, the rising number of proof will enable rational approaches to improving the effectiveness and safety of this modern class of medicine.

Measuring HPV vaccination coverage in Australia: comparing two alternative population-based denominators.

Science.gov (United States)

Barbaro, Bianca; Brotherton, Julia M L

2015-08-01

To compare the use of two alternative population-based denominators in calculating HPV vaccine coverage in Australia by age groups, jurisdiction and remoteness areas. Data from the National HPV Vaccination Program Register (NHVPR) were analysed at Local Government Area (LGA) level, by state/territory and by the Australian Standard Geographical Classification Remoteness Structure. The proportion of females vaccinated was calculated using both the ABS ERP and Medicare enrolments as the denominator. HPV vaccine coverage estimates were slightly higher using Medicare enrolments than using the ABS estimated resident population nationally (70.8% compared with 70.4% for 12 to 17-year-old females, and 33.3% compared with 31.9% for 18 to 26-year-old females, respectively.) The greatest differences in coverage were found in the remote areas of Australia. There is minimal difference between coverage estimates made using the two denominators except in Remote and Very Remote areas where small residential populations make interpretation more difficult. Adoption of Medicare enrolments for the denominator in the ongoing program would make minimal, if any, difference to routine coverage estimates. © 2015 Public Health Association of Australia.

TUMOUR VACCINE

NARCIS (Netherlands)

Wagner, Ernst; Kircheis, Ralf; Crommelin, D.; Van Slooten, Maaike; Storm, Gert

1999-01-01

The invention relates to a tumour vaccine with a tumour antigen base. In addition to a source of tumour antigens, the vaccine contains a release system for the delayed release of the active agent IFN- gamma , the active dose of IFN- gamma being 50 ng to 5 mu g. The IFN- gamma is released over a

Analysis of hepatitis B vaccination behavior and vaccination willingness among migrant workers from rural China based on protection motivation theory.

Science.gov (United States)

Liu, Rugang; Li, Youwei; Wangen, Knut R; Maitland, Elizabeth; Nicholas, Stephen; Wang, Jian

2016-05-03

With China's accelerating urbanization, migrant workers comprise up to 40% of the urban population of China's largest cities. More mobile than non-migrant urban dwellers, migrants are more likely to contract and spread hepatitis B (HB) than non-migrants. Due to the mandatory system of household registration (hukou), migrants are less likely to be covered by national HB immunization programs and also to have more limited access to public health services where they work than non-migrants. Migrants form a significant sub-group in all Chinese cities posing unique public policy vaccination challenges. Using protection motivation theory (PMT), we developed and measured HB cognitive variables and analyze the factors affecting HB vaccination behavior and willingness to vaccinate by migrant workers. We propose public policy interventions to increase HB vaccination rates of migrant workers. We developed a questionnaire to collect information on the HB vaccination characteristics of 1684 respondents from 6 provinces and Beijing. Exploratory factor analysis was used to create PMT variables and a binary logistic regression model was used to analyze the factors affecting migrant workers' HB vaccination behavior and willingness to vaccinate. Vulnerability and response-efficacy were significant PMT cognition factors determining HB vaccination behavior. The HB vaccination rate for migrants decreased with increasing age and was smaller for the primary education than the high education group. The vaccination rate of the medical insurance group was significantly greater than the non-insured group, and the vaccination probability was significantly higher for the self-rated good health compared to the self-rated poor health group. Geographical birth location mattered: the vaccination rate for Beijing city and Ningxia province migrants were higher than for Hebei province and the vaccination rate was lower for migrants born far from health facilities compared to those located middle

Serology and longevity of immunity against Echinococcus granulosus in sheep and llama induced by an oil-based EG95 vaccine.

Science.gov (United States)

Poggio, T V; Jensen, O; Mossello, M; Iriarte, J; Avila, H G; Gertiser, M L; Serafino, J J; Romero, S; Echenique, M A; Dominguez, D E; Barrios, J R; Heath, D

2016-08-01

An oil-based formulation of the EG95 vaccine to protect grazing animals against infection with Echinococcus granulosus was formulated in Argentina. The efficacy of the vaccine was monitored by serology in sheep and llama (Lama glama) and was compared to the serology in sheep previously published using a QuilA-adjuvanted vaccine. Long-term efficacy was also tested in sheep by challenging with E. granulosus eggs of the G1 strain 4 years after the beginning of the trial. The serological results for both sheep and llama were similar to those described previously, except that there was a more rapid response after the first vaccination. A third vaccination given after 1 year resulted in a transient boost in serology that lasted for about 12 months, which was similar to results previously described. Sheep challenged after 4 years with three vaccinations presented 84·2% reduction of live cysts counts compared with control group, and after a fourth vaccination prior to challenge, this reduction was 94·7%. The oil-based vaccine appeared to be bio-equivalent to the QuilA vaccine. © 2016 John Wiley & Sons Ltd.

Differential Adverse Event Profiles Associated with BCG as a Preventive Tuberculosis Vaccine or Therapeutic Bladder Cancer Vaccine Identified by Comparative Ontology-Based VAERS and Literature Meta-Analysis.

Directory of Open Access Journals (Sweden)

Jiangan Xie

Full Text Available M. bovis strain Bacillus Calmette-Guérin (BCG has been the only licensed live attenuated vaccine against tuberculosis (TB for nearly one century and has also been approved as a therapeutic vaccine for bladder cancer treatment since 1990. During its long time usage, different adverse events (AEs have been reported. However, the AEs associated with the BCG preventive TB vaccine and therapeutic cancer vaccine have not been systematically compared. In this study, we systematically collected various BCG AE data mined from the US VAERS database and PubMed literature reports, identified statistically significant BCG-associated AEs, and ontologically classified and compared these AEs related to these two types of BCG vaccine. From 397 VAERS BCG AE case reports, we identified 64 AEs statistically significantly associated with the BCG TB vaccine and 14 AEs with the BCG cancer vaccine. Our meta-analysis of 41 peer-reviewed journal reports identified 48 AEs associated with the BCG TB vaccine and 43 AEs associated with the BCG cancer vaccine. Among all identified AEs from VAERS and literature reports, 25 AEs belong to serious AEs. The Ontology of Adverse Events (OAE-based ontological hierarchical analysis indicated that the AEs associated with the BCG TB vaccine were enriched in immune system (e.g., lymphadenopathy and lymphadenitis, skin (e.g., skin ulceration and cyanosis, and respiratory system (e.g., cough and pneumonia; in contrast, the AEs associated with the BCG cancer vaccine mainly occurred in the urinary system (e.g., dysuria, pollakiuria, and hematuria. With these distinct AE profiles detected, this study also discovered three AEs (i.e., chills, pneumonia, and C-reactive protein increased shared by the BCG TB vaccine and bladder cancer vaccine. Furthermore, our deep investigation of 24 BCG-associated death cases from VAERS identified the important effects of age, vaccine co-administration, and immunosuppressive status on the final BCG

Immunogenicity and protective efficacy of Semliki forest virus replicon-based DNA vaccines encoding goatpox virus structural proteins

International Nuclear Information System (INIS)

Zheng Min; Jin Ningyi; Liu Qi; Huo Xiaowei; Li Yang; Hu Bo; Ma Haili; Zhu Zhanbo; Cong Yanzhao; Li Xiao; Jin Minglan; Zhu Guangze

2009-01-01

Goatpox, caused by goatpox virus (GTPV), is an acute feverish and contagious disease in goats often associated with high morbidity and high mortality. To resolve potential safety risks and vaccination side effects of existing live attenuated goatpox vaccine (AV41), two Semliki forest virus (SFV) replicon-based bicistronic expression DNA vaccines (pCSm-AAL and pCSm-BAA) which encode GTPV structural proteins corresponding to the Vaccinia virus proteins A27, L1, A33, and B5, respectively, were constructed. Then, theirs ability to induce humoral and cellular response in mice and goats, and protect goats against virulent virus challenge were evaluated. The results showed that, vaccination with pCSm-AAL and pCSm-BAA in combination could elicit strong humoral and cellular responses in mice and goats, provide partial protection against viral challenge in goats, and reduce disease symptoms. Additionally, priming vaccination with the above-mentioned DNA vaccines could significantly reduce the goats' side reactions from boosting vaccinations with current live vaccine (AV41), which include skin lesions at the inoculation site and fevers. Data obtained in this study could not only facilitate improvement of the current goatpox vaccination strategy, but also provide valuable guidance to suitable candidates for evaluation and development of orthopoxvirus vaccines.

Ebolavirus Vaccines: Progress in the Fight Against Ebola Virus Disease.

Science.gov (United States)

Wu, Xiao-Xin; Yao, Hang-Ping; Wu, Nan-Ping; Gao, Hai-Nv; Wu, Hai-Bo; Jin, Chang-Zhong; Lu, Xiang-Yun; Xie, Tian-Shen; Li, Lan-Juan

2015-01-01

Ebolaviruses are highly infectious pathogens that cause lethal Ebola virus disease (EVD) in humans and non-human primates (NHPs). Due to their high pathogenicity and transmissibility, as well as the potential to be misused as a bioterrorism agent, ebolaviruses would threaten the health of global populations if not controlled. In this review, we describe the origin and structure of ebolaviruses and the development of vaccines from the beginning of the 1980s, including conventional ebolavirus vaccines, DNA vaccines, Ebola virus-like particles (VLPs), vaccinia virus-based vaccines, Venezuelan equine encephalitis virus (VEEV)-like replicon particles, Kunjin virus-based vaccine, recombinant Zaire Ebolavirusx2206;VP30, recombinant cytomegalovirus (CMV)-based vaccines, recombinant rabies virus (RABV)-based vaccines, recombinant paramyxovirus-based vaccines, adenovirus-based vaccines and vesicular stomatitis virus (VSV)-based vaccines. No licensed vaccine or specific treatment is currently available to counteract ebolavirus infection, although DNA plasmids and several viral vector approaches have been evaluated as promising vaccine platforms. These vaccine candidates have been confirmed to be successful in protecting NHPs against lethal infection. Moreover, these vaccine candidates were successfully advanced to clinical trials. The present review provides an update of the current research on Ebola vaccines, with the aim of providing an overview on current prospects in the fight against EVD. © 2015 The Author(s) Published by S. Karger AG, Basel.

Cell culture based production of avian influenza vaccines

NARCIS (Netherlands)

Wielink, van R.

2012-01-01

Vaccination of poultry can be used as a tool to control outbreaks of avian influenza, including that of highly pathogenic H5 and H7 strains. Influenza vaccines are traditionally produced in embryonated chicken eggs. Continuous cell lines have been suggested as an alternative substrate to produce

A school-based human papillomavirus vaccination program in barretos, Brazil: final results of a demonstrative study.

Directory of Open Access Journals (Sweden)

José Humberto Tavares Guerreiro Fregnani

Full Text Available The implementation of a public HPV vaccination program in several developing countries, especially in Latin America, is a great challenge for health care specialists.To evaluate the uptake and the three-dose completion rates of a school-based HPV vaccination program in Barretos (Brazil.THE STUDY INCLUDED GIRLS WHO WERE ENROLLED IN PUBLIC AND PRIVATE SCHOOLS AND WHO REGULARLY ATTENDED THE SIXTH AND SEVENTH GRADES OF ELEMENTARY SCHOOL (MEAN AGE: 11.9 years. A meeting with the parents or guardians occurred approximately one week before the vaccination in order to explain the project and clarify the doubts. The quadrivalent vaccine was administered using the same schedule as in the product package (0-2-6 months. The school visits for regular vaccination occurred on previously scheduled dates. The vaccine was also made available at Barretos Cancer Hospital for the girls who could not be vaccinated on the day when the team visited the school.Among the potential candidates for vaccination (n = 1,574, the parents or guardians of 1,513 girls (96.1% responded to the invitation to participate in the study. A total of 1,389 parents or guardians agreed to participate in the program (acceptance rate = 91.8%. The main reason for refusing to participate in the vaccination program was fear of adverse events. The vaccine uptake rates for the first, second, and third doses were 87.5%, 86.3% and 85.0%, respectively. The three-dose completion rate was 97.2%.This demonstrative study achieved high rates of vaccination uptake and completion of three vaccine doses in children 10-16 years old from Brazil. The feasibility and success of an HPV vaccination program for adolescents in a developing country may depend on the integration between the public health and schooling systems.

Preserved immunogenicity of an inactivated vaccine based on foot-and-mouth disease virus particles with improved stability.

Science.gov (United States)

Caridi, Flavia; Vázquez-Calvo, Ángela; Borrego, Belén; McCullough, Kenneth; Summerfield, Artur; Sobrino, Francisco; Martín-Acebes, Miguel A

2017-05-01

Foot-and-mouth disease virus (FMDV) is the etiological agent of a highly contagious disease that affects important livestock species. Vaccines based on inactivated FMDV virions provide a useful tool for the control of this pathogen. However, long term storage at 4°C (the temperature for vaccine storage) or ruptures of the cold chain, provoke the dissociation of virions, reducing the immunogenicity of the vaccine. An FMDV mutant carrying amino acid replacements VP1 N17D and VP2 H145Y isolated previously rendered virions with increased resistance to dissociation at 4°C. We have evaluated the immunogenicity in swine (a natural FMDV host) of a chemically inactivated vaccine based on this mutant. The presence of these amino acid substitutions did not compromise the immunological potential, including its ability to elicit neutralizing antibodies. These results support the feasibility of this kind of mutants with increased capsid stability as suitable viruses for producing improved FMDV vaccines. Copyright © 2017 Elsevier B.V. All rights reserved.

Challenges in conducting a community-based influenza vaccine trial in a rural community in northern India.

Science.gov (United States)

Kumar, Rakesh; Amarchand, Ritvik; Narayan, Venkatesh Vinayak; Saha, Siddhartha; Lafond, Kathryn E; Kapoor, Suresh K; Dar, Lalit; Jain, Seema; Krishnan, Anand

2018-04-04

Evidence on influenza vaccine effectiveness from low and middle countries (LMICs) is limited due to limited institutional capacities; lack of adequate resources; and lack of interest by ministries of health for influenza vaccine introduction. There are concerns that the highest ethical standards will be compromised during trials in LMICs leading to mistrust of clinical trials. These factors pose regulatory and operational challenges to researchers in these countries. We conducted a community-based vaccine trial to assess the efficacy of live attenuated influenza vaccine and inactivated influenza vaccine in rural north India. Key regulatory challenges included obtaining regulatory approvals, reporting of adverse events, and compensating subjects for trial-related injuries; all of which were required to be completed in a timely fashion. Key operational challenges included obtaining audio-visual consent; maintaining a low attrition rate; and administering vaccines during a narrow time period before the influenza season, and under extreme heat. We overcame these challenges through advanced planning, and sustaining community engagement. We adapted the trial procedures to cope with field conditions by conducting mock vaccine camps; and planned for early morning vaccination to mitigate threats to the cold chain. These lessons may help investigators to confront similar challenges in other LMICs.

Development of a Multivalent Subunit Vaccine against Tularemia Using Tobacco Mosaic Virus (TMV Based Delivery System.

Directory of Open Access Journals (Sweden)

Sukalyani Banik

Full Text Available Francisella tularensis is a facultative intracellular pathogen, and is the causative agent of a fatal human disease known as tularemia. F. tularensis is classified as a Category A Biothreat agent by the CDC based on its use in bioweapon programs by several countries in the past and its potential to be used as an agent of bioterrorism. No licensed vaccine is currently available for prevention of tularemia. In this study, we used a novel approach for development of a multivalent subunit vaccine against tularemia by using an efficient tobacco mosaic virus (TMV based delivery platform. The multivalent subunit vaccine was formulated to contain a combination of F. tularensis protective antigens: OmpA-like protein (OmpA, chaperone protein DnaK and lipoprotein Tul4 from the highly virulent F. tularensis SchuS4 strain. Two different vaccine formulations and immunization schedules were used. The immunized mice were challenged with lethal (10xLD100 doses of F. tularensis LVS on day 28 of the primary immunization and observed daily for morbidity and mortality. Results from this study demonstrate that TMV can be used as a carrier for effective delivery of multiple F. tularensis antigens. TMV-conjugate vaccine formulations are safe and multiple doses can be administered without causing any adverse reactions in immunized mice. Immunization with TMV-conjugated F. tularensis proteins induced a strong humoral immune response and protected mice against respiratory challenges with very high doses of F. tularensis LVS. This study provides a proof-of-concept that TMV can serve as a suitable platform for simultaneous delivery of multiple protective antigens of F. tularensis. Refinement of vaccine formulations coupled with TMV-targeting strategies developed in this study will provide a platform for development of an effective tularemia subunit vaccine as well as a vaccination approach that may broadly be applicable to many other bacterial pathogens.

Can opportunities be enhanced for vaccinating children in home visiting programs? A population-based cohort study.

Science.gov (United States)

Isaac, Michael R; Chartier, Mariette; Brownell, Marni; Chateau, Dan; Nickel, Nathan C; Martens, Patricia; Katz, Alan; Sarkar, Joykrishna; Hu, Milton; Burland, Elaine; Goh, ChunYan; Taylor, Carole

2015-07-07

Home visiting programs focused on improving early childhood environments are commonplace in North America. A goal of many of these programs is to improve the overall health of children, including promotion of age appropriate vaccination. In this study, population-based data are used to examine the effect of a home visiting program on vaccination rates in children. Home visiting program data from Manitoba, Canada were linked to several databases, including a provincial vaccination registry to examine vaccination rates in a cohort of children born between 2003 and 2009. Propensity score weights were used to balance potential confounders between a group of children enrolled in the program (n = 4,562) and those who were eligible but not enrolled (n = 5,184). Complete and partial vaccination rates for one and two year old children were compared between groups, including stratification into area-level income quintiles. Complete vaccination rates from birth to age 1 and 2 were higher for those enrolled in the Families First program [Average Treatment Effect Risk Ratio (ATE RR) 1.06 (95 % CI 1.03-1.08) and 1.10 (95 % CI 1.05-1.15) respectively]. No significant differences were found between groups having at least one vaccination at age 1 or 2 [ATE RR 1.01 (95 % CI 1.00-1.02) and 1.00 (95 % CI 1.00-1.01) respectively). The interaction between program and income quintiles was not statistically significant suggesting that the program effect did not differ by income quintile. Home visiting programs have the potential to increase vaccination rates for children enrolled, despite limited program content directed towards this end. Evidence-based program enhancements have the potential to increase these rates further, however more research is needed to inform policy makers of optimal approaches in this regard, especially with respect to cost-effectiveness.

A Multiplex Microsphere-Based Immunoassay Increases the Sensitivity of SIV-Specific Antibody Detection in Serum Samples and Mucosal Specimens Collected from Rhesus Macaques Infected with SIVmac239

OpenAIRE

Powell, Rebecca L.R.; Ouellette, Ian; Lindsay, Ross W.; Parks, Christopher L.; King, C. Richter; McDermott, Adrian B.; Morrow, Gavin

2013-01-01

Abstract Results from recent HIV-1 vaccine studies have indicated that high serum antibody (Ab) titers may not be necessary for Ab-mediated protection, and that Abs localized to mucosal sites might be critical for preventing infection. Enzyme-linked immunosorbent assay (ELISA) has been used for decades as the gold standard for Ab measurement, though recently, highly sensitive microsphere-based assays have become available, with potential utility for improved detection of Abs. In this study, w...

Glycoconjugate Vaccines: The Regulatory Framework.

Science.gov (United States)

Jones, Christopher

2015-01-01

Most vaccines, including the currently available glycoconjugate vaccines, are administered to healthy infants, to prevent future disease. The safety of a prospective vaccine is a key prerequisite for approval. Undesired side effects would not only have the potential to damage the individual infant but also lead to a loss of confidence in the respective vaccine-or vaccines in general-on a population level. Thus, regulatory requirements, particularly with regard to safety, are extremely rigorous. This chapter highlights regulatory aspects on carbohydrate-based vaccines with an emphasis on analytical approaches to ensure the consistent quality of successive manufacturing lots.

The impact of non-financial and financial encouragements on participation in non school-based human papillomavirus vaccination: a retrospective cohort study.

Science.gov (United States)

Lefevere, Eva; Hens, Niel; De Smet, Frank; Beutels, Philippe

2016-04-01

Adolescent vaccination coverage under a system of non school-based vaccination is likely to be suboptimal, but might be increased by targeted encouragement campaigns. We analysed the effect on human papillomavirus (HPV) vaccination initiation by girls aged 12-18 of two campaigns set up in Flanders (Belgium) in 2007 and 2009: a personal information campaign and a combined personal information and financial incentive campaign. We analysed (objective) data on HPV vaccination behaviour from the National Alliance of Christian Mutualities (NACM), Flanders' largest sickness fund. We used z-scores to compare the monthly proportion of girls initiating HPV vaccination over time between carefully selected intervention and control groups. Separate analyses were done for older and younger girls. Total sample sizes of the intervention (control) groups were 221 (243) for the personal information campaign and 629 (5,322) for the combined personal information and financial incentive campaign. The personal information campaign significantly increased vaccination initiation, with older girls reacting faster. One year after the campaign the percentages of vaccination initiation for the oldest girls were 64.6 and 42.8 % in the intervention and control group, respectively (z = 3.35, p = 0.0008); for the youngest girls the percentages were 78.4 and 68.1 % (z = 1.71, p = 0.09). The combined personal information and financial incentive campaign increased vaccination initiation among certain age groups. One year after the campaign the difference in percentage points for HPV vaccination initiation between intervention and control groups varied between 18.5 % (z = 3.65, p = 0.0002) and 5.1 % (z = 1.12, p = 0.26). Under a non school-based vaccination system, personal information and removing out-of-pocket costs had a significant positive effect on HPV vaccination initiation, although the effect substantially varied in magnitude. Overall, the obtained vaccination rates remained far below those

Green revolution vaccines, edible vaccines

African Journals Online (AJOL)

Admin

of development. Food vaccines may also help to suppress autoimmunity disorders such as Type-1. Diabetes. Key words: Edible vaccines, oral vaccines, antigen expression, food vaccines. INTRODUCTION. Vaccination involves the stimulation of the immune system to prepare it for the event of an invasion from a particular ...

A Threat- and Efficacy-Based Framework to Understand Confidence in Vaccines among the Public Health Workforce

Directory of Open Access Journals (Sweden)

Lainie Rutkow

2013-04-01

Full Text Available The Extended Parallel Process Model (EPPM is an established threat- and efficacy-based behavioral framework for understanding health behaviors in the face of uncertain risk. A growing body of research has applied this model to understand these behaviors among the public health workforce. In this manuscript, we aim to explore the application of this framework to the public health workforce, with a novel focus on their confidence in vaccines and perceptions of vaccine injury compensation mechanisms. We characterize specific connections between EPPM’s threat and efficacy dimensions and relevant vaccine policy frameworks and highlight how these connections can usefully inform training interventions for public health workers to enhance their confidence in these vaccine policy measures.

Dendrimers for Vaccine and Immunostimulatory Uses

DEFF Research Database (Denmark)

Heegaard, Peter M. H.; Boas, Ulrik; Sørensen, Nanna Skall

2010-01-01

for efficient immunostimulating compounds (adjuvants) that can increase the efficiency of vaccines, as dendrimers can provide molecularly defined multivalent scaffolds to produce highly defined conjugates with small molecule immunostimulators and/or antigens. The review gives an overview on the use...... of dendrimers as molecularly defined carriers/presenters of small antigens, including constructs that have built-in immunostimulatory (adjuvant) properties, and as stand-alone adjuvants that can be mixed with antigens to provide efficient vaccine formulations. These approaches allow the preparation...... of molecularly defined vaccines with highly predictable and specific properties and enable knowledge-based vaccine design substituting the traditional empirically based approaches for vaccine development and production....

Long-Term Single-Dose Efficacy of a Vesicular Stomatitis Virus-Based Andes Virus Vaccine in Syrian Hamsters

Directory of Open Access Journals (Sweden)

Joseph Prescott

2014-01-01

Full Text Available Andes virus (ANDV is highly pathogenic in humans and is the primary etiologic agent of hantavirus cardiopulmonary syndrome (HCPS in South America. Case-fatality rates are as high as 50% and there are no approved vaccines or specific therapies for infection. Our laboratory has recently developed a replication-competent recombinant vesicular stomatitis virus (VSV-based vaccine that expressed the glycoproteins of Andes virus in place of the native VSV glycoprotein (G. This vaccine is highly efficacious in the Syrian hamster model of HCPS when given 28 days before challenge with ANDV, or when given around the time of challenge (peri-exposure, and even protects when administered post-exposure. Herein, we sought to test the durability of the immune response to a single dose of this vaccine in Syrian hamsters. This vaccine was efficacious in hamsters challenged intranasally with ANDV 6 months after vaccination (p = 0.025, but animals were not significantly protected following 1 year of vaccination (p = 0.090. The decrease in protection correlated with a reduction of measurable neutralizing antibody responses, and suggests that a more robust vaccination schedule might be required to provide long-term immunity.

Increased humoral immunity by DNA vaccination using an alpha-tocopherol-based adjuvant

DEFF Research Database (Denmark)

Karlsson, Ingrid; Borggren, Marie; Nielsen, Jens

2017-01-01

approaches. We tested whether the emulsion-based and alpha-tocopherol containing adjuvant Diluvac Forte® has the ability to enhance the immunogenicity of a naked DNA vaccine (i.e., plasmid DNA). As a model vaccine, we used plasmids encoding both a surface-exposed viral glycoprotein (hemagglutinin......) and an internal non-glycosylated nucleoprotein in the Th1/Th2 balanced CB6F1 mouse model. The naked DNA (50 µg) was premixed at a 1:1 volume/volume ratio with Diluvac Forte®, an emulsion containing different concentrations of alpha-tocopherol, the emulsion alone or endotoxin-free phosphate-buffered saline (PBS......). The animals received two intracutaneous immunizations spaced 3 weeks apart. When combined with Diluvac Forte® or the emulsion containing alpha-tocopherol, the DNA vaccine induced a more potent and balanced immunoglobulin G (IgG)1 and IgG2c response, and both IgG subclass responses were significantly enhanced...

Expanding Free School-based Human Papilloma Virus (HPV Vaccination Programs to Include School-aged Males in Nova Scotia, Canada

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Hannah Krater-Melamed

2017-06-01

Full Text Available Bill 70 (HPV Vaccine Act was presented to the Nova Scotia House of Assembly with the aim of expanding the current Nova Scotia school-based HPV vaccination program to include males. In recent years, increased awareness of HPV and HPV-caused cancers has led to the implementation of school-based female HPV vaccination programs across Canada. Changing guidelines, based on recent evidence, suggest that males should also be included in these programs. Program expansion to include males aims to reduce the prevalence of HPV-causing cancers and their ensuing costs, to promote equal access to healthcare services, and to make Nova Scotia a leader in HPV prevention. Support from the Canadian public and high profile political actors along with pressure from other provinces and interest groups, including the Society of Obstetricians and Gynaecologists of Canada, influenced the passing of the HPV Vaccine Act. In order to implement this reform, the provincial financial commitment to the previous HPV program was expanded to cover the cost of male vaccination.

Development of a serology-based assay for efficacy evaluation of a lactococcicosis vaccine in Seriola fish.

Science.gov (United States)

Nakajima, Nao; Kawanishi, Michiko; Imamura, Saiki; Hirano, Fumiya; Uchiyama, Mariko; Yamamoto, Kinya; Nagai, Hidetaka; Futami, Kunihiko; Katagiri, Takayuki; Maita, Masashi; Kijima, Mayumi

2014-05-01

Lactococcicosis is an infection caused by the bacterium Lactococcus garvieae and creates serious economic damage to cultured marine and fresh water fish industries. The use of the assay currently applied to evaluate the potency of the lactococcicosis vaccine is contingent upon meeting specific parameters after statistical analysis of the percent survival of the vaccinated yellowtail or greater amberjack fish after challenge with a virulent strain of L. garvieae. We found that measuring the serological response with a quantitative agglutinating antibody against the L. garvieae antigen (phenotype KG+) was an effective method of monitoring the potency of lactococcicosis vaccines. Vaccinated fish had significantly higher antibody titers than control fish when the L. garvieae Lg2-S strain was used as an antigen. Furthermore, the titer of the KG + agglutinating antibody was correlated with vaccine potency, and the cut-off titer was determined by comparing the data with those from the challenge test. An advantage of the proposed serology-based potency assay is that it will contribute to reduced numbers of animal deaths during vaccine potency evaluations. Copyright © 2014 Elsevier Ltd. All rights reserved.

Vaccine platform recombinant measles virus.

Science.gov (United States)

Mühlebach, Michael D

2017-10-01

The classic development of vaccines is lengthy, tedious, and may not necessarily be successful as demonstrated by the case of HIV. This is especially a problem for emerging pathogens that are newly introduced into the human population and carry the inherent risk of pandemic spread in a naïve population. For such situations, a considerable number of different platform technologies are under development. These are also under development for pathogens, where directly derived vaccines are regarded as too complicated or even dangerous due to the induction of inefficient or unwanted immune responses causing considerable side-effects as for dengue virus. Among platform technologies are plasmid-based DNA vaccines, RNA replicons, single-round infectious vector particles, or replicating vaccine-based vectors encoding (a) critical antigen(s) of the target pathogens. Among the latter, recombinant measles viruses derived from vaccine strains have been tested. Measles vaccines are among the most effective and safest life-attenuated vaccines known. Therefore, the development of Schwarz-, Moraten-, or AIK-C-strain derived recombinant vaccines against a wide range of mostly viral, but also bacterial pathogens was quite straightforward. These vaccines generally induce powerful humoral and cellular immune responses in appropriate animal models, i.e., transgenic mice or non-human primates. Also in the recent first clinical phase I trial, the results have been quite encouraging. The trial indicated the expected safety and efficacy also in human patients, interestingly independent from the level of prevalent anti-measles immunity before the trial. Thereby, recombinant measles vaccines expressing additional antigens are a promising platform for future vaccines.

Distinction between infections with European and American/vaccine type PRRS virus after vaccination with a modified-live PRRS virus vaccine

DEFF Research Database (Denmark)

Bøtner, Anette; Strandbygaard, Bertel; Sørensen, K. J.

2000-01-01

In July 1996 a modified live Porcine reproductive and respiratory syndrome (PRRS) vaccine, based on an American (US) strain of the PRRS virus (PRRSV), was licensed in Denmark. The vaccine was licensed for use in 3-18 week old pigs, exclusively. Starting during the middle of October 1996, several...... herds who had recently begun vaccination, experienced acute PRRS-like symptoms including an increasing number of abortions and stillborn piglets and an increasing mortality in the nursing period. During the period from October 1996 until May 1997, the PRRS virus (PRRSV), identified as the vaccine....../US type of PRRSV, was isolated from fetuses, dead piglets, pleural fluids and/or lung tissues from 114 of such herds. These findings indicated the spread of the vaccine virus to non-vaccinated sows followed by transplacental infection of fetuses. Also, a number of not previously PRRSV infected and non...

Design and implementation of a children vaccination reminder system based on short message service

Directory of Open Access Journals (Sweden)

Marjan Ghazisaeedi

2016-09-01

Full Text Available Background: Most problems related to quality of care and patient safety are related to human negligence. One of the causes of these problems is forgetting to do something. This problem can be avoided with information technology in many cases. Some forgotten are very important. Among these is failure to comply with vaccination schedule by parents that can result in inappropriate outcomes. In this study, we developed and evaluated a SMS reminder system for regular and timely vaccination of children. Methods: In this developmental-applied research, firstly, a child vaccination reminder system was designed and implemented to help parents reduce the forgetfulness. This system based on the child's vaccination history and the date of birth, offer time and type of future vaccines. Then the parents of 27 children, that their vaccination was between 22 June and 21 August 2015, referred to Children's Medical Center, were sent text messages by using this system. We evaluated the accuracy of the system logic by using some scenarios. In addition, we evaluated parents' satisfaction with the system using a questionnaire. Results: In all cases but one, the system proposed the type and date of future children vaccines correctly. All the parents who have received text messages had good perception and satisfaction on the majority of questions (total mean score of 4.15 out of 5. Most parents (4.92 out of 5 stated that using the system to remind their visit for child immunization was helpful and willing to offer the system to their friends and other families. Conclusion: Using the short message system is beneficial for parents to remind their children’s vaccination time and increases their satisfaction. So, it can be considered as an important and essential tool in providing healthcare services. SMS is an easy, cheap and effective way to improve the quality of care services.

Nanotechnology and vaccine development

Directory of Open Access Journals (Sweden)

Mi-Gyeong Kim

2014-10-01

Full Text Available Despite the progress of conventional vaccines, improvements are clearly required due to concerns about the weak immunogenicity of these vaccines, intrinsic instability in vivo, toxicity, and the need for multiple administrations. To overcome such problems, nanotechnology platforms have recently been incorporated into vaccine development. Nanocarrier-based delivery systems offer an opportunity to enhance the humoral and cellular immune responses. This advantage is attributable to the nanoscale particle size, which facilitates uptake by phagocytic cells, the gut-associated lymphoid tissue, and the mucosa-associated lymphoid tissue, leading to efficient antigen recognition and presentation. Modifying the surfaces of nanocarriers with a variety of targeting moieties permits the delivery of antigens to specific cell surface receptors, thereby stimulating specific and selective immune responses. In this review, we introduce recent advances in nanocarrier-based vaccine delivery systems, with a focus on the types of carriers, including liposomes, emulsions, polymer-based particles, and carbon-based nanomaterials. We describe the remaining challenges and possible breakthroughs, including the development of needle-free nanotechnologies and a fundamental understanding of the in vivo behavior and stability of the nanocarriers in nanotechnology-based delivery systems.

Elementary School-Based Influenza Vaccination: Evaluating Impact on Respiratory Illness Absenteeism and Laboratory-Confirmed Influenza

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Kjos, Sonia A.; Irving, Stephanie A.; Meece, Jennifer K.; Belongia, Edward A.

2013-01-01

Background Studies of influenza vaccine effectiveness in schools have assessed all-cause absenteeism rather than laboratory-confirmed influenza. We conducted an observational pilot study to identify absences due to respiratory illness and laboratory-confirmed influenza in schools with and without school-based vaccination. Methods A local public health agency initiated school-based influenza vaccination in two Wisconsin elementary schools during October 2010 (exposed schools); two nearby schools served as a comparison group (non-exposed schools). Absences due to fever or cough illness were monitored for 12 weeks. During the 4 weeks of peak influenza activity, parents of absent children with fever/cough illness were contacted and offered influenza testing. Results Parental consent for sharing absenteeism data was obtained for 937 (57%) of 1,640 students. Fifty-two percent and 28%, respectively, of all students in exposed and non-exposed schools were vaccinated. Absences due to fever or cough illness were significantly lower in the exposed schools during seven of 12 surveillance weeks. Twenty-seven percent of students at exposed schools and 39% at unexposed schools had one or more days of absence due to fever/cough illness (pabsenteeism due to fever or cough illness, but not absenteeism for other reasons. Although nonspecific, absence due to fever or cough illness may be a useful surrogate endpoint in school-based studies if identification of laboratory confirmed influenza is not feasible. PMID:23991071

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

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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.

Vaccines. An Ebola whole-virus vaccine is protective in nonhuman primates.

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Marzi, Andrea; Halfmann, Peter; Hill-Batorski, Lindsay; Feldmann, Friederike; Shupert, W Lesley; Neumann, Gabriele; Feldmann, Heinz; Kawaoka, Yoshihiro

2015-04-24

Zaire ebolavirus is the causative agent of the current outbreak of hemorrhagic fever disease in West Africa. Previously, we showed that a whole Ebola virus (EBOV) vaccine based on a replication-defective EBOV (EBOVΔVP30) protects immunized mice and guinea pigs against lethal challenge with rodent-adapted EBOV. Here, we demonstrate that EBOVΔVP30 protects nonhuman primates against lethal infection with EBOV. Although EBOVΔVP30 is replication-incompetent, we additionally inactivated the vaccine with hydrogen peroxide; the chemically inactivated vaccine remained antigenic and protective in nonhuman primates. EBOVΔVP30 thus represents a safe, efficacious, whole-EBOV vaccine candidate that differs from other EBOV vaccine platforms in that it presents all viral proteins and the viral RNA to the host immune system, which might contribute to protective immune responses. Copyright © 2015, American Association for the Advancement of Science.

Effectiveness and acceptance of a health care-based mandatory vaccination program.

Science.gov (United States)

Leibu, Rachel; Maslow, Joel

2015-01-01

To decrease the risk of transmission of hospital-associated transmission of influenza and pertussis through mandatory vaccination of staff. A mandatory influenza and toxoid-diphtheria toxoid-acellular pertussis program was implemented systemwide. A structured vaccine exemption program was implemented for those requesting a medical and/or religious/moral/ethical exemption. Systemwide influenza vaccination rates increased from 67% historically, 76.2% in the 2012 to 2013 influenza season, to 94.7% in 2013 to 2014 with an overall compliance rate of 97.8%. Toxoid-diphtheria toxoid-acellular pertussis vaccination rates systemwide reached 94.9%, with an overall compliance rate of 98%. Higher rates were experienced at individual hospital facilities compared with the corporate location. Successful vaccination campaign outcomes can be achieved through diligent enforcement of mandatory vaccination, masking, and other infection prevention procedures.

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

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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. PMID:28819449

Reproductive toxicity testing of vaccines

International Nuclear Information System (INIS)

Verdier, Francois; Barrow, Paul C.; Burge, Joeelle

2003-01-01

Vaccines play a major role in the prevention of human birth defects by protecting the pregnant woman from teratogenic or otherwise harmful infections. Until now, it has not been common practice to perform preclinical developmental toxicity tests for new vaccines. Despite the excellent safety record of vaccines, increased attention is now being given to the feasibility of screening new vaccines for developmental hazards in animals before their use in humans. Contrary to previous assumptions, many vaccines are now given to potentially pregnant women. Any new components of the vaccine formulation (adjuvants, excipients, stabilisers, preservatives, etc...) could also be tested for influences on development, although based on past experience the risks are limited by the very low dosages used. The conferred immunity following vaccination lasts for several years. Therefore, the developing conceptus may theoretically be exposed to the induced antibodies and/or sensitised T-cells, even if the pregnant woman was last vaccinated during childhood (particularly if she encounters the antigen during pregnancy through exposure to infection). However, it should be kept in mind that viral or bacterial infections represent a higher risk for a pregnant woman than the potential adverse effects related to vaccination or the associated immune response. Non-clinical safety studies may be employed as an aid for hazard identification. In these studies interactions of the vaccine with the maternal immune system or with the developmental systems of the offspring are considered. Post-natal examinations are necessary to detect all possible manifestations of developmental toxicity, such as effects on the immune system. Species selection for the preclinical studies is based on immunogenicity to the vaccine and the relative timing and rate of transfer of maternal antibodies to the offspring. A single study design is proposed for the pre- and post-natal developmental assessments of vaccines in

Self-amplifying mRNA vaccines.

Science.gov (United States)

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.

Future of an “Asymptomatic” T-cell Epitope-Based Therapeutic Herpes Simplex Vaccine

Science.gov (United States)

Dervillez, Xavier; Gottimukkala, Chetan; Kabbara, Khaled W.; Nguyen, Chelsea; Badakhshan, Tina; Kim, Sarah M.; Nesburn, Anthony B.; Wechsler, Steven L.; BenMohamed, Lbachir

2012-01-01

Summary Considering the limited success of the recent herpes clinical vaccine trial [1], new vaccine strategies are needed. Infections with herpes simplex virus type 1 and type 2 (HSV-1 & HSV-2) in the majority of men and women are usually asymptomatic and results in lifelong viral latency in neurons of sensory ganglia (SG). However, in a minority of men and women HSV spontaneous reactivation can cause recurrent disease (i.e., symptomatic individuals). Our recent findings show that T cells from symptomatic and asymptomatic men and women (i.e. those with and without recurrences, respectively) recognize different herpes epitopes. This finding breaks new ground and opens new doors to assess a new vaccine strategy: mucosal immunization with HSV-1 & HSV-2 epitopes that induce strong in vitro CD4 and CD8 T cell responses from PBMC derived from asymptomatic men and women (designated here as “asymptomatic” protective epitopes”) could boost local and systemic “natural” protective immunity, induced by wild-type infection. Here we highlight the rationale and the future of our emerging “asymptomatic” T cell epitope-based mucosal vaccine strategy to decrease recurrent herpetic disease. PMID:22701511

Endoplasmic reticulum targeting sequence enhances HBV-specific cytotoxic T lymphocytes induced by a CTL epitope-based DNA vaccine

International Nuclear Information System (INIS)

Xu Wei; Chu Yiwei; Zhang Ruihua; Xu Huanbin; Wang Ying; Xiong Sidong

2005-01-01

CD8 + T cells play a critical role in protective immunity against Hepatitis B Virus (HBV). Epitope-based DNA vaccines expressing HBV-dominant CTL epitopes can be used as candidate vaccines capable of inducing cytotoxic T Lymphocytes (CTL) responses. A plasmid DNA encoding a CTL epitope of HBV core antigen, HBc 18-27 , was constructed. Intramuscular immunization of C57BL/6 mice with this DNA vaccine resulted in successful induction of HBV-specific CTL responses. In order to promote transportation of the peptide into endoplasmic reticulum (ER) to bind to MHC class I molecules for optimal class I antigen presentation, an ER targeting sequence (ERTS) was fused with the C 18-27 encoding gene. ERTS fusion significantly enhanced specific CD8 + T cell responses in terms of CTL cytolysis as well as IFN-γ secretion. This enhancement was correlated with promoted epitope presentation on target cell surface. We report here an enhanced immunogenicity of an epitope-based DNA vaccine using an ER targeting signal sequence, which has significant implications for future design of therapeutic HBV vaccine

VIOLIN: vaccine investigation and online information network.

Science.gov (United States)

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.

Vaccines based on the cell surface carbohydrates of pathogenic bacteria

Directory of Open Access Journals (Sweden)

Jones Christopher

2005-01-01

Full Text Available Glycoconjugate vaccines, in which a cell surface carbohydrate from a micro-organism is covalently attached to an appropriate carrier protein are proving to be the most effective means to generate protective immune responses to prevent a wide range of diseases. The technology appears to be generic and applicable to a wide range of pathogens, as long as antibodies against surface carbohydrates help protect against infection. Three such vaccines, against Haemophilus influenzae type b, Neisseria meningitidis Group C and seven serotypes of Streptococcus pneumoniae, have already been licensed and many others are in development. This article discusses the rationale for the development and use of glycoconjugate vaccines, the mechanisms by which they elicit T cell-dependent immune responses and the implications of this for vaccine development, the role of physicochemical methods in the characterisation and quality control of these vaccines, and the novel products which are under development.

Alphavirus-based Vaccines Encoding Nonstructural Proteins of Hepatitis C Virus Induce Robust and Protective T-cell Responses

NARCIS (Netherlands)

Ip, Peng; Boerma, Annemarie; Regts, Joke; Meijerhof, Tjarko; Wilschut, Jan; Nijman, Hans W.; Daemen, Toos

An absolute prerequisite for a therapeutic vaccine against hepatitis C virus (HCV) infection is the potency to induce HCV-specific vigorous and broad-spectrum T-cell responses. Here, we generated three HCV vaccines based on a recombinant Semliki Forest virus (rSFV) vector expressing all-or a part of

Comparing bivalent and quadrivalent human papillomavirus vaccines: economic evaluation based on transmission model.

Science.gov (United States)

Jit, Mark; Chapman, Ruth; Hughes, Owain; Choi, Yoon Hong

2011-09-27

To compare the effect and cost effectiveness of bivalent and quadrivalent human papillomavirus (HPV) vaccination, taking into account differences in licensure indications, protection against non-vaccine type disease, protection against disease related to HPV types 6 and 11, and reported long term immunogenicity. A model of HPV transmission and disease previously used to inform UK vaccination policy, updated with recent evidence and expanded to include scenarios where the two vaccines differ in duration of protection, cross protection, and end points prevented. United Kingdom. Population Males and females aged 12-75 years. Incremental cost effectiveness ratios for both vaccines and additional cost per dose for the quadrivalent vaccine to be equally cost effective as the bivalent vaccine. The bivalent vaccine needs to be cheaper than the quadrivalent vaccine to be equally cost effective, mainly because of its lack of protection against anogenital warts. The price difference per dose ranges from a median of £19 (interquartile range £12-£27) to £35 (£27-£44) across scenarios about vaccine duration, cross protection, and end points prevented (assuming one quality adjusted life year (QALY) is valued at £30,000 and both vaccines can prevent all types of HPV related cancers). The quadrivalent vaccine may have an advantage over the bivalent vaccine in reducing healthcare costs and QALYs lost. The bivalent vaccine may have an advantage in preventing death due to cancer. However, considerable uncertainty remains about the differential benefit of the two vaccines.

Parents' views of including young boys in the Swedish national school-based HPV vaccination programme: a qualitative study.

Science.gov (United States)

Gottvall, Maria; Stenhammar, Christina; Grandahl, Maria

2017-02-28

To explore parents' views of extending the human papillomavirus (HPV) vaccination programme to also include boys. Explorative qualitative design using individual, face-to-face, interviews and inductive thematic analysis. 11 strategically chosen municipalities in central Sweden. Parents (n=42) who were offered HPV vaccination for their 11-12 years old daughter in the national school-based vaccination programme. The key themes were: equality from a public health perspective and perception of risk for disease . Parents expressed low knowledge and awareness about the health benefits of male HPV vaccination, and they perceived low risk for boys to get HPV. Some parents could not see any reason for vaccinating boys. However, many parents preferred gender-neutral vaccination, and some of the parents who had not accepted HPV vaccination for their daughter expressed that they would be willing to accept vaccination for their son, if it was offered. It was evident that there was both trust and distrust in authorities' decision to only vaccinate girls. Parents expressed a preference for increased sexual and reproductive health promotion such as more information about condom use. Some parents shared that it was more important to vaccinate girls than boys since they believed girls face a higher risk of deadly diseases associated with HPV, but some also believed girls might be more vulnerable to side effects of the vaccine. A vaccine offered only to girls may cause parents to be hesitant to vaccinate, while also including boys in the national vaccination programme might improve parents' trust in the vaccine. More information about the health benefits of HPV vaccination for males is necessary to increase HPV vaccination among boys. This may eventually lead to increased HPV vaccine coverage among both girls and boys. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Novel Adjuvants and Immunomodulators for Veterinary Vaccines.

Science.gov (United States)

Heegaard, Peter M H; Fang, Yongxiang; Jungersen, Gregers

2016-01-01

Adjuvants are crucial for efficacy of vaccines, especially subunit and recombinant vaccines. Rational vaccine design, including knowledge-based and molecularly defined adjuvants tailored for directing and potentiating specific types of host immune responses towards the antigens included in the vaccine is becoming a reality with our increased understanding of innate and adaptive immune activation. This will allow future vaccines to induce immune reactivity having adequate specificity as well as protective and recallable immune effector mechanisms in appropriate body compartments, including mucosal surfaces. Here we describe these new developments and, when possible, relate new immunological knowledge to the many years of experience with traditional, empirical adjuvants. Finally, some protocols are given for production of emulsion (oil-based) and liposome-based adjuvant/antigen formulations.

Macromolecular systems for vaccine delivery.

Science.gov (United States)

MuŽíková, G; Laga, R

2016-10-20

Vaccines have helped considerably in eliminating some life-threatening infectious diseases in past two hundred years. Recently, human medicine has focused on vaccination against some of the world's most common infectious diseases (AIDS, malaria, tuberculosis, etc.), and vaccination is also gaining popularity in the treatment of cancer or autoimmune diseases. The major limitation of current vaccines lies in their poor ability to generate a sufficient level of protective antibodies and T cell responses against diseases such as HIV, malaria, tuberculosis and cancers. Among the promising vaccination systems that could improve the potency of weakly immunogenic vaccines belong macromolecular carriers (water soluble polymers, polymer particels, micelles, gels etc.) conjugated with antigens and immunistumulatory molecules. The size, architecture, and the composition of the high molecular-weight carrier can significantly improve the vaccine efficiency. This review includes the most recently developed (bio)polymer-based vaccines reported in the literature.

Vaccine process technology.

Science.gov (United States)

Josefsberg, Jessica O; Buckland, Barry

2012-06-01

The evolution of vaccines (e.g., live attenuated, recombinant) and vaccine production methods (e.g., in ovo, cell culture) are intimately tied to each other. As vaccine technology has advanced, the methods to produce the vaccine have advanced and new vaccine opportunities have been created. These technologies will continue to evolve as we strive for safer and more immunogenic vaccines and as our understanding of biology improves. The evolution of vaccine process technology has occurred in parallel to the remarkable growth in the development of therapeutic proteins as products; therefore, recent vaccine innovations can leverage the progress made in the broader biotechnology industry. Numerous important legacy vaccines are still in use today despite their traditional manufacturing processes, with further development focusing on improving stability (e.g., novel excipients) and updating formulation (e.g., combination vaccines) and delivery methods (e.g., skin patches). Modern vaccine development is currently exploiting a wide array of novel technologies to create safer and more efficacious vaccines including: viral vectors produced in animal cells, virus-like particles produced in yeast or insect cells, polysaccharide conjugation to carrier proteins, DNA plasmids produced in E. coli, and therapeutic cancer vaccines created by in vitro activation of patient leukocytes. Purification advances (e.g., membrane adsorption, precipitation) are increasing efficiency, while innovative analytical methods (e.g., microsphere-based multiplex assays, RNA microarrays) are improving process understanding. Novel adjuvants such as monophosphoryl lipid A, which acts on antigen presenting cell toll-like receptors, are expanding the previously conservative list of widely accepted vaccine adjuvants. As in other areas of biotechnology, process characterization by sophisticated analysis is critical not only to improve yields, but also to determine the final product quality. From a regulatory

Overcoming barriers in HPV vaccination and screening programs

Directory of Open Access Journals (Sweden)

Alex Vorsters

2017-12-01

Full Text Available The Human Papillomavirus Prevention and Control Board brought together experts to discuss optimizing HPV vaccination and screening programs.Board members reviewed the safety profile of licensed HPV vaccines based on clinical and post-marketing data, reaching a consensus that current safety data is reassuring.Successful vaccination programs used well-coordinated communication campaigns, integrating (social media to spread awareness. Communication of evidence supporting vaccine effectiveness had beneficial effects on the perception of the vaccine. However, anti-vaccination campaigns have threatened existing programs in many countries.Measurement and monitoring of HPV vaccine confidence over time could help understand the nature and scale of waning confidence, define issues and intervene appropriately using context-specific evidence-based strategies. Finally, a broad group of stakeholders, such as teachers, health care providers and the media should also be provided with accurate information and training to help support prevention efforts through enhanced understanding of the risks and benefits of vaccination.Similarly, while cervical cancer screening through population-based programs is highly effective, barriers to screening exist: awareness in countries with population-based screening programs, access for vulnerable populations, and access and affordability in low- and middle-income countries. Integration of primary and secondary prevention has the potential to accelerate the decrease in cervical cancer incidence. Keywords: (max 6 Human papillomavirus, Vaccine, Screening, Barriers, Vaccine confidence

Polyethylenimine-based polyplex delivery of self-replicating RNA vaccines.

Science.gov (United States)

Démoulins, Thomas; Milona, Panagiota; Englezou, Pavlos C; Ebensen, Thomas; Schulze, Kai; Suter, Rolf; Pichon, Chantal; Midoux, Patrick; Guzmán, Carlos A; Ruggli, Nicolas; McCullough, Kenneth C

2016-04-01

Self-amplifying replicon RNA (RepRNA) are large molecules (12-14 kb); their self-replication amplifies mRNA template numbers, affording several rounds of antigen production, effectively increasing vaccine antigen payloads. Their sensitivity to RNase-sensitivity and inefficient uptake by dendritic cells (DCs) - absolute requirements for vaccine design - were tackled by condensing RepRNA into synthetic, nanoparticulate, polyethylenimine (PEI)-polyplex delivery vehicles. Polyplex-delivery formulations for small RNA molecules cannot be transferred to RepRNA due to its greater size and complexity; the N:P charge ratio and impact of RepRNA folding would influence polyplex condensation, post-delivery decompaction and the cytosolic release essential for RepRNA translation. Polyplex-formulations proved successful for delivery of RepRNA encoding influenza virus hemagglutinin and nucleocapsid to DCs. Cytosolic translocation was facilitated, leading to RepRNA translation. This efficacy was confirmed in vivo, inducing both humoral and cellular immune responses. Accordingly, this paper describes the first PEI-polyplexes providing efficient delivery of the complex and large, self-amplifying RepRNA vaccines. The use of self-amplifying replicon RNA (RepRNA) to increase vaccine antigen payloads can potentially be useful in effective vaccine design. Nonetheless, its use is limited by the degradation during the uptake process. Here, the authors attempted to solve this problem by packaging RepRNA using polyethylenimine (PEI)-polyplex delivery vehicles. The efficacy was confirmed in vivo by the appropriate humoral and cellular immune responses. This novel delivery method may prove to be very useful for future vaccine design. Copyright © 2015 Elsevier Inc. All rights reserved.

Rotavirus vaccination and herd immunity: an evidence-based review

Directory of Open Access Journals (Sweden)

Seybolt LM

2012-06-01

Full Text Available Lorna M Seybolt, Rodolfo E BéguéDepartment of Pediatrics, Division of Infectious Diseases, Louisiana State University Health Sciences Center, New Orleans, LA, USAAbstract: Until recently, rotavirus was the most common cause of diarrhea in infants and young children with over 100 million cases and 400,000 deaths every year worldwide. Yet, its epidemiology is changing rapidly with the introduction of two rotavirus vaccines in the mid 2000s. Both vaccines were shown to be highly efficacious in prelicensure studies to reduce severe rotavirus disease; the efficacy being more pronounced in high- and middle-income countries than in low-income countries. Herd immunity – the indirect protection of unimmunized individuals as a result of others being immunized – was not expected to be a benefit of rotavirus vaccination programs since the vaccines were thought to reduce severe disease but not to decrease virus transmission significantly. Postlicensure studies, however, have suggested that this assumption may need reassessment. Studies in a variety of settings have shown evidence of greater than expected declines in rotavirus disease. While these studies were not designed specifically to detect herd immunity – and few failed to detect this phenomenon – the consistency of the evidence is compelling. These studies are reviewed and described here. While further work is needed, clarifying the presence of herd immunity is not just an academic exercise but an important issue for rotavirus control, especially in lower income countries where the incidence of the disease is highest and the direct protection of the vaccines is lower.Keywords: rotavirus, vaccine, herd immunity, efficacy

Nuclear Magnetic Resonance: new applications in the quantification and assessment of polysaccharide-based vaccine intermediates

International Nuclear Information System (INIS)

Garrido, Raine; Velez, Herman; Verez, Vicente

2013-01-01

Nuclear Magnetic Resonance has become the choice for structural studies, identity assays and simultaneous quantification of active pharmaceutical ingredient of different polysaccharide-based vaccine. In the last two decades, the application of quantitative Nuclear Magnetic Resonance had an increasing impact to support several quantification necessities. The technique involves experiments with several modified parameters in order to obtain spectra with quantifiable signals. The present review is supported by some recent relevant reports and it discusses several applications of NMR in carbohydrate-based vaccines. Moreover, it emphasizes and describes several parameters and applications of quantitative Nuclear Magnetic Resonance

Designing and modeling of complex DNA vaccine based on tropomyosin protein of Boophilus genus tick.

Science.gov (United States)

Ranjbar, Mohamamd Mahdi; Gupta, Shishir K; Ghorban, Khodayar; Nabian, Sedigheh; Sazmand, Alireza; Taheri, Mohammad; Esfandyari, Sahar; Taheri, Maryam

2015-01-01

Boophilus tick is a bloodsucking ectoparasite that transfers some pathogens, reducing production and thus leading to economical losses in the cattle industry. Tropomyosin (TPM) protein is a salivary protein, has actin regulator activity, and plays an important role in immune reactions against parasites. In the current study, besides developing a safe, effective, and broad spectrum protective measure against Boophilus genus tick based on TPM protein, we attempted to minimize possible problems occurring in the design of polytopic vaccines. Briefly, the steps that were followed in the present study were as follows: retrieving sequences and finding the mutational/conservative regions, selecting consensus and high immunogenic epitopes of B and CD4(+) T cells by different approaches, three-dimensional structure (3D structure) prediction and representation of epitopes and highly variable/conserve regions, designing vaccinal construct by fusion of B and T cell epitopes by special patterns and improving immunogenicity, evaluation of the constructs' primary structure and posttranslational modification, calculation of hydrophobic regions, reverse translation, codon optimization, open reading frame checking, insertion of start/end codon, Kozak sequence, and finally constructing the DNA vaccine. Variation plot showed some shared epitopes among the ticks' and mites' species that some might be effective only in some species. Finally, by following the steps mentioned above, two constructs for B and T cells were achieved. Checking constructs revealed their reliability and efficacy for in vitro production and utilization. Successful in silico modeling is an essential step of designing vigorous vaccines. We developed a novel protective and therapeutic vaccine against Boophilus genus (based on TPM protein). At the next step, constructed DNA vaccine would be produced in vitro and administrated to cattle, and its potency to induction of immune response and protection against Boophilus

MFR-vaccination og autisme - et populationsbaseret followupstudie

DEFF Research Database (Denmark)

Madsen, Kreesten Meldgaard; Hviid, Anders; Vestergaard, Mogens

2002-01-01

Summary: Summary A population-based study of measles, mumps, and rubella vaccination and autism. Ugeskr Læger 2002; 164: 5741-4. Introduction: It has been suggested that the measles-mumps-rubella (MMR) vaccination causes autism. Material and methods: We conducted a retrospective cohort study of all...... confidence interval, 0.65 to 1.07). There was no association between age at vaccination, time since vaccination or calendar period at time of vaccination and development of autistic disorder. Discussion: This study provides strong evidence against the hypothesis that MMR vaccination causes autism....... children born in Denmark from January 1991 through December 1998. The cohort was established based on data from the Danish Civil Registration System. A unique person identifiable number given to all subjects enabled linkage with other national registries. MMR vaccination status was obtained from the Danish...

Novel vaccination approach for dengue infection based on recombinant immune complex universal platform.

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Kim, Mi-Young; Reljic, Rajko; Kilbourne, Jacquelyn; Ceballos-Olvera, Ivonne; Yang, Moon-Sik; Reyes-del Valle, Jorge; Mason, Hugh S

2015-04-08

Dengue infection is on the rise in many endemic areas of the tropics. Vaccination remains the most realistic strategy for prevention of this potentially fatal viral disease but there is currently no effective vaccine that could protect against all four known serotypes of the dengue virus. This study describes the generation and testing of a novel vaccination approach against dengue based on recombinant immune complexes (RIC). We modelled the dengue RIC on the existing Ebola RIC (Phoolcharoen, et al. Proc Natl Acad Sci USA 2011;108(Dec (51)):20695) but with a key modification that allowed formation of a universal RIC platform that can be easily adapted for use for other pathogens. This was achieved by retaining only the binding epitope of the 6D8 ant-Ebola mAb, which was then fused to the consensus dengue E3 domain (cEDIII), resulting in a hybrid dengue-Ebola RIC (DERIC). We expressed human and mouse versions of these molecules in tobacco plants using a geminivirus-based expression system. Following purification from the plant extracts by protein G affinity chromatography, DERIC bound to C1q component of complement, thus confirming functionality. Importantly, following immunization of mice, DERIC induced a potent, virus-neutralizing anti-cEDIII humoral immune response without exogenous adjuvants. We conclude that these self-adjuvanting immunogens have the potential to be developed as a novel vaccine candidate for dengue infection, and provide the basis for a universal RIC platform for use with other antigens. Copyright © 2015 Elsevier Ltd. All rights reserved.

Prophylactic Hepatitis E Vaccine.

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Zhang, Jun; Zhao, Qinjian; Xia, Ningshao

2016-01-01

Hepatitis E has been increasingly recognized as an underestimated global disease burden in recent years. Subpopulations with more serious infection-associated damage or death include pregnant women, patients with basic liver diseases, and elderly persons. Vaccine would be the most effective means for prevention of HEV infection. The lack of an efficient cell culture system for HEV makes the development of classic inactive or attenuated vaccine infeasible. Hence, the recombinant vaccine approaches are explored deeply. The neutralizing sites are located almost exclusively in the capsid protein, pORF2, of the virion. Based on pORF2, many vaccine candidates showed potential of protecting primate animals; two of them were tested in human and evidenced to be well tolerated in adults and highly efficacious in preventing hepatitis E. The world's first hepatitis E vaccine, Hecolin ® (HEV 239 vaccine), was licensed in China and launched in 2012.

Vaccines and Kawasaki disease.

Science.gov (United States)

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.

Feasibility of using global system for mobile communication (GSM)-based tracking for vaccinators to improve oral poliomyelitis vaccine campaign coverage in rural Pakistan.

Science.gov (United States)

Chandir, Subhash; Dharma, Vijay Kumar; Siddiqi, Danya Arif; Khan, Aamir Javed

2017-09-05

Despite multiple rounds of immunization campaigns, it has not been possible to achieve optimum immunization coverage for poliovirus in Pakistan. Supplementary activities to improve coverage of immunization, such as door-to-door campaigns are constrained by several factors including inaccurate hand-drawn maps and a lack of means to objectively monitor field teams in real time, resulting in suboptimal vaccine coverage during campaigns. Global System for Mobile Communications (GSM) - based tracking of mobile subscriber identity modules (SIMs) of vaccinators provides a low-cost solution to identify missed areas and ensure effective immunization coverage. We conducted a pilot study to investigate the feasibility of using GSM technology to track vaccinators through observing indicators including acceptability, ease of implementation, costs and scalability as well as the likelihood of ownership by District Health Officials. The real-time location of the field teams was displayed on a GSM tracking web dashboard accessible by supervisors and managers for effective monitoring of workforce attendance including 'time in-time out', and discerning if all target areas - specifically remote and high-risk locations - had been reached. Direct access to this information by supervisors eliminated the possibility of data fudging and inaccurate reporting by workers regarding their mobility. The tracking cost per vaccinator was USD 0.26/month. Our study shows that GSM-based tracking is potentially a cost-efficient approach, results in better monitoring and accountability, is scalable and provides the potential for improved geographic coverage of health services. Copyright © 2017 Elsevier Ltd. All rights reserved.

Household-based costs and benefits of vaccinating healthy children in daycare against influenza virus: results from a pilot study.

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Pisu, Maria; Meltzer, Martin I; Hurwitz, Eugene S; Haber, Michael

2005-01-01

Vaccinating children against influenza virus may reduce infections in immunised children and household contacts, thereby reducing the household-based cost associated with respiratory illnesses. To evaluate the impact of influenza virus vaccination of daycare children on costs of respiratory illnesses of the children and their household contacts from the household and societal perspective. Cost analysis of data from a randomised controlled trial covering the period November to April of 1996-7 and 1998-9. Children (127 in 1996-7 and 133 in 1998-9) from daycare centres in Californian (USA) naval bases received influenza virus vaccine (inactivated) or hepatitis A virus vaccination. Direct and indirect costs (1997 and 1999 US dollars) of respiratory illnesses in households of vaccinated and not vaccinated daycare children, excluding the cost of vaccination. There were no statistically significant differences in household costs of respiratory illness between households with or without influenza virus-vaccinated children (USD 635 vs USD 492: p = 0.98 [1996-7]; USD 412.70 vs USD 499.50: p = 0.42 [1998-9]). In 1996-7, adult and 5- to 17-year-old contacts of vaccinated children had lower household costs than contacts of unvaccinated children (USD 58.50 vs USD 83.20, p = 0.01 and USD 32.80 vs USD 59.50, p = 0.04, respectively), while vaccinated children 0-4 years old had higher household costs than unvaccinated children in the same age group (USD 383 vs USD 236, p = 0.05). In 1998-9, there were no differences within individual age groups. Results from societal perspective were similar. Overall, from both the household and societal perspectives, there were no economic benefits to households from vaccinating daycare children against influenza virus. However, we found some over-time inconsistency in results; this should be considered if changing recommendations about routine influenza virus vaccination of healthy children. Our study size may limit the generalisability of the

Promoting Influenza Vaccination to Restaurant Employees.

Science.gov (United States)

Graves, Meredith C; Harris, Jeffrey R; Hannon, Peggy A; Hammerback, Kristen; Parrish, Amanda T; Ahmed, Faruque; Zhou, Chuan; Allen, Claire L

2016-09-01

To evaluate an evidence-based workplace approach to increasing adult influenza vaccination levels applied in the restaurant setting We implemented an intervention and conducted a pre/post analysis to determine effect on vaccination. Eleven Seattle-area restaurants. Restaurants with 25+ employees speaking English or Spanish and over 18 years. Restaurants received influenza vaccination promotion materials, assistance arranging on-site vaccination events, and free influenza vaccinations for employees. Pre/post employee surveys of vaccination status with direct observation and employer interviews to evaluate implementation. We conducted descriptive analysis of employee survey data and performed qualitative analysis of implementation data. To assess intervention effect, we used a mixed-effects logistic regression model with a restaurant-specific random effect. Vaccination levels increased from 26% to 46% (adjusted odds ratio 2.33, 95% confidence interval 1.69, 3.22), with 428 employees surveyed preintervention, 305 surveyed postintervention, and response rates of 73% and 55%, respectively. The intervention was effective across subgroups, but there were restaurant-level differences. An access-based workplace intervention can increase influenza vaccination levels in restaurant employees, but restaurant-level factors may influence success. © 2016 by American Journal of Health Promotion, Inc.

Bacterium-like Particles for efficient immune stimulation of existing vaccines and new subunit vaccines in mucosal applications

Directory of Open Access Journals (Sweden)

Natalija eVan Braeckel-Budimir

2013-09-01

Full Text Available The successful development of a mucosal vaccine critically depends on the use of a safe and effective immunostimulant and/or carrier system. This review describes the effectiveness and mode of action of an immunostimulating particle derived from bacteria in mucosal subunit vaccines. The non-living particles, designated Bacterium-like Particles (BLPs are based on the food-grade bacterium Lactococcus lactis. The focus of the overview is on the development of intranasal BLP-based vaccines to prevent diseases caused by influenza and respiratory syncytial virus, and includes a selection of Phase I clinical data for the intranasal FluGEM vaccine.

SAFETY OF CELL-DERIVED SUBUNIT ADJUVANTED INFLUENZA VACCINE FOR CHILDREN VACCINATION: DOUBLE-BLIND RANDOMIZED CLINICAL TRIAL

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S.M. Kharit

2010-01-01

Full Text Available This article presents the safety data for cell-derived inactivated subunit adjuvanted influenza vaccine «Grippol Neo» in children 3–17 years old in comparison with reference egg-derived inactivated subunit vaccine «Grippol plus». Good test vaccine tolerability and high efficacy profile is demonstrated. Based on the results obtained vaccine «Grippol Neo» is recommended for mass influenza prophylaxis in pediatry, including National Immunization Schedule.Key words: children, influenza, vaccination, «Grippol Neo».(Voprosy sovremennoi pediatrii — Current Pediatrics. – 2010;9(4:44-49

Intranasal delivery of nanoparticle-based vaccine increases protection against S. pneumoniae

Energy Technology Data Exchange (ETDEWEB)

Mott, Brittney [University of North Texas Health Science Center, Department of Molecular Biology and Immunology (United States); Thamake, Sanjay [Radio-Isotope Therapy of America Foundation (United States); Vishwanatha, Jamboor; Jones, Harlan P., E-mail: harlan.jones@unthsc.edu [University of North Texas Health Science Center, Department of Molecular Biology and Immunology (United States)

2013-05-15

Nanoparticle (NP) technologies are becoming commonplace in the development of vaccine delivery systems to protect against various diseases. The current study determined the efficacy of intranasal delivery of a 234 {+-} 87.5 nm poly lactic-co-glycolic acid nanoparticle vaccine construct in establishing protection against experimental respiratory pneumococcal infection. Nanoparticles encapsulating heat-killed Streptococcus pneumoniae (NP-HKSP) were retained in the lungs 11 days following nasal administration compared to empty NP. Immunization with NP-HKSP produced significant resistance against S. pneumoniae infection compared to administration of HKSP alone. Increased protection correlated with a significant increase in antigen-specific Th1-associated IFN-{gamma} cytokine response by pulmonary lymphocytes. This study establishes the efficacy of NP-based technology as a non-invasive and targeted approach for nasal-pulmonary immunization against pulmonary infections.

Intranasal delivery of nanoparticle-based vaccine increases protection against S. pneumoniae

International Nuclear Information System (INIS)

Mott, Brittney; Thamake, Sanjay; Vishwanatha, Jamboor; Jones, Harlan P.

2013-01-01

Nanoparticle (NP) technologies are becoming commonplace in the development of vaccine delivery systems to protect against various diseases. The current study determined the efficacy of intranasal delivery of a 234 ± 87.5 nm poly lactic-co-glycolic acid nanoparticle vaccine construct in establishing protection against experimental respiratory pneumococcal infection. Nanoparticles encapsulating heat-killed Streptococcus pneumoniae (NP-HKSP) were retained in the lungs 11 days following nasal administration compared to empty NP. Immunization with NP-HKSP produced significant resistance against S. pneumoniae infection compared to administration of HKSP alone. Increased protection correlated with a significant increase in antigen-specific Th1-associated IFN-γ cytokine response by pulmonary lymphocytes. This study establishes the efficacy of NP-based technology as a non-invasive and targeted approach for nasal-pulmonary immunization against pulmonary infections.

Intranasal delivery of nanoparticle-based vaccine increases protection against S. pneumoniae

Science.gov (United States)

Mott, Brittney; Thamake, Sanjay; Vishwanatha, Jamboor; Jones, Harlan P.

2013-05-01

Nanoparticle (NP) technologies are becoming commonplace in the development of vaccine delivery systems to protect against various diseases. The current study determined the efficacy of intranasal delivery of a 234 ± 87.5 nm poly lactic-co-glycolic acid nanoparticle vaccine construct in establishing protection against experimental respiratory pneumococcal infection. Nanoparticles encapsulating heat-killed Streptococcus pneumoniae (NP-HKSP) were retained in the lungs 11 days following nasal administration compared to empty NP. Immunization with NP-HKSP produced significant resistance against S. pneumoniae infection compared to administration of HKSP alone. Increased protection correlated with a significant increase in antigen-specific Th1-associated IFN-γ cytokine response by pulmonary lymphocytes. This study establishes the efficacy of NP-based technology as a non-invasive and targeted approach for nasal-pulmonary immunization against pulmonary infections.

Vaccines against invasive Salmonella disease

Science.gov (United States)

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

2014-01-01

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

Community-based interventions to improve HPV vaccination coverage among 13- to 15-year-old females: measures implemented by local governments in Japan.

Directory of Open Access Journals (Sweden)

Hiroyuki Fujiwara

Full Text Available The purpose of this study was to examine the effect of various community-based interventions in support of HPV vaccination implemented by cities and towns within Tochigi prefecture, Japan with a view to identifying useful indicators which might guide future interventions to improve HPV vaccination coverage in the prefecture. A postal questionnaire survey of all 27 local governments in Tochigi Prefecture was conducted in December 2010. All 27 responded, and 22 provided the exact numbers of the targeted and vaccinated populations of 13- to 15-year-old girls from April to December 2010. The local governments also answered questions on the type of interventions implemented including public subsidies, school-based programs, direct mail, free tickets and recalls. Local governments that conducted a school-based vaccination program reported 96.8% coverage for the 1(st dose, 96.2% for the 2(nd dose, and 91.2% for the 3(rd dose. Those that provided subsidies without school-based programs reported a wide range of vaccination rates: 45.7%-95.0% for the 1(st dose, 41.1%-93.7% for the 2(nd dose and 3.1%-90.1% for the 3(rd dose. Among this group, the combination of a free ticket, direct mail and recall was most effective, with 95.0% coverage for the 1(st dose, 93.7% for the 2(nd dose, and 90.1% for the 3(rd dose. The governments that did not offer a subsidy had the lowest vaccination coverage, with 0.8%-1.4% for the 1(st dose, 0.0%-0.8% for the 2(nd dose, and 0.1%-0.1% for the 3(rd dose. The results of this survey indicate that school-based vaccinations and public subsidies are the most effective method to improve HPV vaccination coverage; however, the combination of a free ticket, direct mail, and recalls with public subsidies are also important measures in increasing the vaccination rate. These data may afford important indicators for the successful implementation of future HPV vaccination programs.

Vaccine decision-making begins in pregnancy: Correlation between vaccine concerns, intentions and maternal vaccination with subsequent childhood vaccine uptake.

Science.gov (United States)

Danchin, M H; Costa-Pinto, J; Attwell, K; Willaby, H; Wiley, K; Hoq, M; Leask, J; Perrett, K P; O'Keefe, Jacinta; Giles, M L; Marshall, H

2017-08-12

Maternal and childhood vaccine decision-making begins prenatally. Amongst pregnant Australian women we aimed to ascertain vaccine information received, maternal immunisation uptake and attitudes and concerns regarding childhood vaccination. We also aimed to determine any correlation between a) intentions and concerns regarding childhood vaccination, (b) concerns about pregnancy vaccination, (c) socioeconomic status (SES) and (d) uptake of influenza and pertussis vaccines during pregnancy and routine vaccines during childhood. Women attending public antenatal clinics were recruited in three Australian states. Surveys were completed on iPads. Follow-up phone surveys were done three to six months post delivery, and infant vaccination status obtained via the Australian Childhood Immunisation Register (ACIR). Between October 2015 and March 2016, 975 (82%) of 1184 mothers consented and 406 (42%) agreed to a follow up survey, post delivery. First-time mothers (445; 49%) had significantly more vaccine concerns in pregnancy and only 73% had made a decision about childhood vaccination compared to 89% of mothers with existing children (p-valuepost delivery survey, 46% and 82% of mothers reported receiving pregnancy influenza and pertussis vaccines respectively. The mother's degree of vaccine hesitancy and two attitudinal factors were correlated with vaccine uptake post delivery. There was no association between reported maternal vaccine uptake or SES and childhood vaccine uptake. First time mothers are more vaccine hesitant and undecided about childhood vaccination, and only two thirds of all mothers believed they received enough information during pregnancy. New interventions to improve both education and communication on childhood and maternal vaccines, delivered by midwives and obstetricians in the Australian public hospital system, may reduce vaccine hesitancy for all mothers in pregnancy and post delivery, particularly first-time mothers. Copyright © 2017 Elsevier Ltd

Future prospects for the development of cost-effective Adenovirus vaccines

DEFF Research Database (Denmark)

Fougeroux, Cyrielle; Holst, Peter J

2017-01-01

-vectored vaccine technology with a focus on adenoviral-based vaccines. Adenovirus (Ad) vaccines have proven to be efficient in military vaccinations against Ad4 and Ad7 and as highly efficient vectored vaccines against rabies. The question of how other adenovirus-based vaccines can become as efficient...... as the rabies vaccine is the underlying theme in this review. Here, we will first give an overview of the basic properties of vectored vaccines, followed by an introduction to the characteristics of adenoviral vectors and previously tested modifications of the vector backbone and expression cassettes...

Vesicular stomatitis virus-based ebola vaccine is well-tolerated and protects immunocompromised nonhuman primates.

Directory of Open Access Journals (Sweden)

Thomas W Geisbert

2008-11-01

Full Text Available Ebola virus (EBOV is a significant human pathogen that presents a public health concern as an emerging/re-emerging virus and as a potential biological weapon. Substantial progress has been made over the last decade in developing candidate preventive vaccines that can protect nonhuman primates against EBOV. Among these prospects, a vaccine based on recombinant vesicular stomatitis virus (VSV is particularly robust, as it can also confer protection when administered as a postexposure treatment. A concern that has been raised regarding the replication-competent VSV vectors that express EBOV glycoproteins is how these vectors would be tolerated by individuals with altered or compromised immune systems such as patients infected with HIV. This is especially important as all EBOV outbreaks to date have occurred in areas of Central and Western Africa with high HIV incidence rates in the population. In order to address this concern, we evaluated the safety of the recombinant VSV vector expressing the Zaire ebolavirus glycoprotein (VSVDeltaG/ZEBOVGP in six rhesus macaques infected with simian-human immunodeficiency virus (SHIV. All six animals showed no evidence of illness associated with the VSVDeltaG/ZEBOVGP vaccine, suggesting that this vaccine may be safe in immunocompromised populations. While one goal of the study was to evaluate the safety of the candidate vaccine platform, it was also of interest to determine if altered immune status would affect vaccine efficacy. The vaccine protected 4 of 6 SHIV-infected macaques from death following ZEBOV challenge. Evaluation of CD4+ T cells in all animals showed that the animals that succumbed to lethal ZEBOV challenge had the lowest CD4+ counts, suggesting that CD4+ T cells may play a role in mediating protection against ZEBOV.

Pre-clinical evaluation of a novel nanoemulsion-based hepatitis B mucosal vaccine.

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Paul E Makidon

2008-08-01

Full Text Available Hepatitis B virus infection remains an important global health concern despite the availability of safe and effective prophylactic vaccines. Limitations to these vaccines include requirement for refrigeration and three immunizations thereby restricting use in the developing world. A new nasal hepatitis B vaccine composed of recombinant hepatitis B surface antigen (HBsAg in a novel nanoemulsion (NE adjuvant (HBsAg-NE could be effective with fewer administrations.Physical characterization indicated that HBsAg-NE consists of uniform lipid droplets (349+/-17 nm associated with HBsAg through electrostatic and hydrophobic interactions. Immunogenicity of HBsAg-NE vaccine was evaluated in mice, rats and guinea pigs. Animals immunized intranasally developed robust and sustained systemic IgG, mucosal IgA and strong antigen-specific cellular immune responses. Serum IgG reached > or = 10(6 titers and was comparable to intramuscular vaccination with alum-adjuvanted vaccine (HBsAg-Alu. Normalization showed that HBsAg-NE vaccination correlates with a protective immunity equivalent or greater than 1000 IU/ml. Th1 polarized immune response was indicated by IFN-gamma and TNF-alpha cytokine production and elevated levels of IgG(2 subclass of HBsAg-specific antibodies. The vaccine retains full immunogenicity for a year at 4 degrees C, 6 months at 25 degrees C and 6 weeks at 40 degrees C. Comprehensive pre-clinical toxicology evaluation demonstrated that HBsAg-NE vaccine is safe and well tolerated in multiple animal models.Our results suggest that needle-free nasal immunization with HBsAg-NE could be a safe and effective hepatitis B vaccine, or provide an alternative booster administration for the parenteral hepatitis B vaccines. This vaccine induces a Th1 associated cellular immunity and also may provide therapeutic benefit to patients with chronic hepatitis B infection who lack cellular immune responses to adequately control viral replication. Long-term stability

Prime-boost vaccination with heterologous live vectors encoding SIV gag and multimeric HIV-1 gp160 protein: efficacy against repeated mucosal R5 clade C SHIV challenges.

Science.gov (United States)

Lakhashe, Samir K; Velu, Vijayakumar; Sciaranghella, Gaia; Siddappa, Nagadenahalli B; Dipasquale, Janet M; Hemashettar, Girish; Yoon, John K; Rasmussen, Robert A; Yang, Feng; Lee, Sandra J; Montefiori, David C; Novembre, Francis J; Villinger, François; Amara, Rama Rao; Kahn, Maria; Hu, Shiu-Lok; Li, Sufen; Li, Zhongxia; Frankel, Fred R; Robert-Guroff, Marjorie; Johnson, Welkin E; Lieberman, Judy; Ruprecht, Ruth M

2011-08-05

We sought to induce primate immunodeficiency virus-specific cellular and neutralizing antibody (nAb) responses in rhesus macaques (RM) through a bimodal vaccine approach. RM were immunized intragastrically (i.g.) with the live-attenuated Listeria monocytogenes (Lm) vector Lmdd-BdopSIVgag encoding SIVmac239 gag. SIV Gag-specific cellular responses were boosted by intranasal and intratracheal administration of replication-competent adenovirus (Ad5hr-SIVgag) encoding the same gag. To broaden antiviral immunity, the RM were immunized with multimeric HIV clade C (HIV-C) gp160 and HIV Tat. SIV Gag-specific cellular immune responses and HIV-1 nAb developed in some RM. The animals were challenged intrarectally with five low doses of R5 SHIV-1157ipEL-p, encoding a heterologous HIV-C Env (22.1% divergent to the Env immunogen). All five controls became viremic. One out of ten vaccinees was completely protected and another had low peak viremia. Sera from the completely and partially protected RM neutralized the challenge virus > 90%; these RM also had strong SIV Gag-specific proliferation of CD8⁺ T cells. Peak and area under the curve of plasma viremia (during acute phase) among vaccinees was lower than for controls, but did not attain significance. The completely protected RM showed persistently low numbers of the α4β7-expressing CD4⁺ T cells; the latter have been implicated as preferential virus targets in vivo. Thus, vaccine-induced immune responses and relatively lower numbers of potential target cells were associated with protection. Copyright © 2011 Elsevier Ltd. All rights reserved.

Modeling the cost-effectiveness of infant vaccination with pneumococcal conjugate vaccines in Germany.

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Kuhlmann, Alexander; von der Schulenburg, J-Matthias Graf

2017-04-01

In 2009, the European Medicines Agency granted approval for two higher-valent pneumococcal conjugate vaccines. This study aims to evaluate the cost-effectiveness of universal infant (historical vaccination scheme in infants as well as indirect herd effects and replacement disease. We used German epidemiological data to calculate episodes of IPD, PNE, and AOM, as well as direct and indirect effects of the vaccination. Parameter uncertainty was tested in univariate and probabilistic sensitivity analyses. In the base-case analysis, the ICER of PCV13 versus PCV10 infant vaccination was EUR 9826 per quality-adjusted life-year (QALY) gained or EUR 5490 per life-year (LY) gained from the societal perspective and EUR 3368 per QALY gained or EUR 1882 per LY gained from the perspective of the German statutory health insurance. The results were particularly sensitive to the magnitude of indirect effects of both vaccines. Universal infant vaccination with PCV13 is likely to be a cost-effective intervention compared with PCV10 within the German health care system, if additional net indirect effects of PCV13 vaccination are significant.

A comparative analysis of influenza vaccination programs.

Directory of Open Access Journals (Sweden)

Shweta Bansal

2006-10-01

Full Text Available BACKGROUND: The threat of avian influenza and the 2004-2005 influenza vaccine supply shortage in the United States have sparked a debate about optimal vaccination strategies to reduce the burden of morbidity and mortality caused by the influenza virus. METHODS AND FINDINGS: We present a comparative analysis of two classes of suggested vaccination strategies: mortality-based strategies that target high-risk populations and morbidity-based strategies that target high-prevalence populations. Applying the methods of contact network epidemiology to a model of disease transmission in a large urban population, we assume that vaccine supplies are limited and then evaluate the efficacy of these strategies across a wide range of viral transmission rates and for two different age-specific mortality distributions. We find that the optimal strategy depends critically on the viral transmission level (reproductive rate of the virus: morbidity-based strategies outperform mortality-based strategies for moderately transmissible strains, while the reverse is true for highly transmissible strains. These results hold for a range of mortality rates reported for prior influenza epidemics and pandemics. Furthermore, we show that vaccination delays and multiple introductions of disease into the community have a more detrimental impact on morbidity-based strategies than mortality-based strategies. CONCLUSIONS: If public health officials have reasonable estimates of the viral transmission rate and the frequency of new introductions into the community prior to an outbreak, then these methods can guide the design of optimal vaccination priorities. When such information is unreliable or not available, as is often the case, this study recommends mortality-based vaccination priorities.

Outsmart HPV: Acceptability and short-term effects of a web-based HPV vaccination intervention for young adult gay and bisexual men.

Science.gov (United States)

McRee, Annie-Laurie; Shoben, Abigail; Bauermeister, Jose A; Katz, Mira L; Paskett, Electra D; Reiter, Paul L

2018-01-10

Effective interventions to promote human papillomavirus (HPV) vaccination are needed, particularly among populations at increased risk of HPV-related disease. We developed and pilot tested a web-based intervention, Outsmart HPV, to promote HPV vaccination among young gay and bisexual men (YGBM). In 2016, we recruited a national sample (n = 150) of YGBM ages 18-25 in the United States who had not received any doses of HPV vaccine. Participants were randomized to receive either standard HPV vaccination information (control) or population-targeted, individually-tailored content (Outsmart HPV intervention). We assessed between group differences in HPV vaccination attitudes and beliefs immediately following the intervention using multiple linear regression. There were no differences in HPV vaccination attitudes, beliefs and intentions between groups at baseline. Compared to participants in the control group, intervention participants reported: greater perception that men who have sex with men are at higher risk for anal cancer relative to other men (b = 0.34); greater HPV vaccination self-efficacy (b = 0.15); and fewer perceived harms of HPV vaccine (b = -0.34) on posttest surveys (all p HPV intervention (all > 4.4 on a 5-point scale). Findings from this study provide preliminary support for a brief, tailored web-based intervention in improving HPV vaccination attitudes and beliefs among YGBM. An important next step is to determine the effects of Outsmart HPV on HPV vaccine uptake. ClinicalTrials.gov identifier NCT02835755. Copyright © 2018 Elsevier Ltd. All rights reserved.

Effective cancer vaccine platform based on attenuated salmonella and a type III secretion system.

Science.gov (United States)

Xu, Xin; Hegazy, Wael A H; Guo, Linjie; Gao, Xiuhua; Courtney, Amy N; Kurbanov, Suhrab; Liu, Daofeng; Tian, Gengwen; Manuel, Edwin R; Diamond, Don J; Hensel, Michael; Metelitsa, Leonid S

2014-11-01

Vaccines explored for cancer therapy have been based generally on injectable vector systems used to control foreign infectious pathogens, to which the immune system evolved to respond naturally. However, these vectors may not be effective at presenting tumor-associated antigens (TAA) to the immune system in a manner that is sufficient to engender antitumor responses. We addressed this issue with a novel orally administered Salmonella-based vector that exploits a type III secretion system to deliver selected TAA in the cytosol of professional antigen-presenting cells in situ. A systematic comparison of candidate genes from the Salmonella Pathogenicity Island 2 (SPI2) locus was conducted in the vaccine design, using model antigens and a codon-optimized form of the human TAA survivin (coSVN), an oncoprotein that is overexpressed in most human cancers. In a screen of 20 SPI2 promoter:effector combinations, a PsifB::sseJ combination exhibited maximal potency for antigen translocation into the APC cytosol, presentation to CD8 T cells, and murine immunogenicity. In the CT26 mouse model of colon carcinoma, therapeutic vaccination with a lead PsifB::sseJ-coSVN construct (p8032) produced CXCR3-dependent infiltration of tumors by CD8 T cells, reversed the CD8:Treg ratio at the tumor site, and triggered potent antitumor activity. Vaccine immunogenicity and antitumor potency were enhanced by coadministration of the natural killer T-cell ligand 7DW8-5, which heightened the production of IL12 and IFNγ. Furthermore, combined treatment with p8032 and 7DW8-5 resulted in complete tumor regression in A20 lymphoma-bearing mice, where protective memory was demonstrated. Taken together, our results demonstrate how antigen delivery using an oral Salmonella vector can provide an effective platform for the development of cancer vaccines. ©2014 American Association for Cancer Research.

High-yield production of a stable Vero cell-based vaccine candidate against the highly pathogenic avian influenza virus H5N1

International Nuclear Information System (INIS)

Zhou, Fangye; Zhou, Jian; Ma, Lei; Song, Shaohui; Zhang, Xinwen; Li, Weidong; Jiang, Shude; Wang, Yue; Liao, Guoyang

2012-01-01

Highlights: ► Vero cell-based HPAI H5N1 vaccine with stable high yield. ► Stable high yield derived from the YNVa H3N2 backbone. ► H5N1/YNVa has a similar safety and immunogenicity to H5N1delta. -- Abstract: Highly pathogenic avian influenza (HPAI) viruses pose a global pandemic threat, for which rapid large-scale vaccine production technology is critical for prevention and control. Because chickens are highly susceptible to HPAI viruses, the supply of chicken embryos for vaccine production might be depleted during a virus outbreak. Therefore, developing HPAI virus vaccines using other technologies is critical. Meeting vaccine demand using the Vero cell-based fermentation process has been hindered by low stability and yield. In this study, a Vero cell-based HPAI H5N1 vaccine candidate (H5N1/YNVa) with stable high yield was achieved by reassortment of the Vero-adapted (Va) high growth A/Yunnan/1/2005(H3N2) (YNVa) virus with the A/Anhui/1/2005(H5N1) attenuated influenza vaccine strain (H5N1delta) using the 6/2 method. The reassorted H5N1/YNVa vaccine maintained a high hemagglutination (HA) titer of 1024. Furthermore, H5N1/YNVa displayed low pathogenicity and uniform immunogenicity compared to that of the parent virus.

Vaccines for Prevention of Cervical Cancer

International Nuclear Information System (INIS)

Mahomed, M.F.

2017-01-01

The characteristics of two prophylactic Human Papilloma Virus HPV vaccines and ethical issues related to HPV vaccination are reviewed in this paper. These vaccines have the potential of substantially reducing HPV-related morbidity and mortality, and in particular cervical cancer. The vaccines cannot treat women with current HPV infection or HPV related disease. They should be administered before the commencement of sexual activity. The ideal age group is adolescent girls between the ages 9-13. Both vaccines are highly efficacious and immunogenic and induce high levels of serum antibodies after three doses for all vaccine-related HPV types. School-based vaccination is considered as a costeffective method for its delivery. Adequate education of both clinicians and patients is an essential to ensure effective implementation when considering a national vaccination program. (author)

Novel GMO-Based Vaccines against Tuberculosis: State of the Art and Biosafety Considerations.

Science.gov (United States)

Leunda, Amaya; Baldo, Aline; Goossens, Martine; Huygen, Kris; Herman, Philippe; Romano, Marta

2014-06-16

Novel efficient vaccines are needed to control tuberculosis (TB), a major cause of morbidity and mortality worldwide. Several TB vaccine candidates are currently in clinical and preclinical development. They fall into two categories, the one of candidates designed as a replacement of the Bacille Calmette Guérin (BCG) to be administered to infants and the one of sub-unit vaccines designed as booster vaccines. The latter are designed as vaccines that will be administered to individuals already vaccinated with BCG (or in the future with a BCG replacement vaccine). In this review we provide up to date information on novel tuberculosis (TB) vaccines in development focusing on the risk assessment of candidates composed of genetically modified organisms (GMO) which are currently evaluated in clinical trials. Indeed, these vaccines administered to volunteers raise biosafety concerns with respect to human health and the environment that need to be assessed and managed.

Schools as potential vaccination venue for vaccines outside regular EPI schedule: results from a school census in Pakistan.

Science.gov (United States)

Soofi, Sajid Bashir; Haq, Inam-Ul; Khan, M Imran; Siddiqui, Muhammad Bilal; Mirani, Mushtaq; Tahir, Rehman; Hussain, Imtiaz; Puri, Mahesh K; Suhag, Zamir Hussain; Khowaja, Asif R; Lasi, Abdul Razzaq; Clemens, John D; Favorov, Michael; Ochiai, R Leon; Bhutta, Zulfiqar A

2012-01-06

Vaccines are the most effective public health intervention. Expanded Program on Immunization (EPI) provides routine vaccination in developing countries. However, vaccines that cannot be given in EPI schedule such as typhoid fever vaccine need alternative venues. In areas where school enrolment is high, schools provide a cost effective opportunity for vaccination. Prior to start of a school-based typhoid vaccination program, interviews were conducted with staff of educational institutions in two townships of Karachi, Pakistan to collect baseline information about the school system and to plan a typhoid vaccination program. Data collection teams administered a structured questionnaire to all schools in the two townships. The administrative staff was requested information on school fee, class enrolment, past history of involvement and willingness of parents to participate in a vaccination campaign. A total of 304,836 students were enrolled in 1,096 public, private, and religious schools (Madrasahs) of the two towns. Five percent of schools refused to participate in the school census. Twenty-five percent of schools had a total enrolment of less than 100 students whereas 3% had more than 1,000 students. Health education programs were available in less than 8% of public schools, 17% of private schools, and 14% of Madrasahs. One-quarter of public schools, 41% of private schools, and 43% of Madrasahs had previously participated in a school-based vaccination campaign. The most common vaccination campaign in which schools participated was Polio eradication program. Cost of the vaccine, side effects, and parents' lack of information were highlighted as important limiting factors by school administration for school-based immunization programs. Permission from parents, appropriateness of vaccine-related information, and involvement of teachers were considered as important factors to improve participation. Health education programs are not part of the regular school curriculum

Schools as potential vaccination venue for vaccines outside regular EPI schedule: results from a school census in Pakistan

Directory of Open Access Journals (Sweden)

Soofi Sajid

2012-01-01

Full Text Available Abstract Background Vaccines are the most effective public health intervention. Expanded Program on Immunization (EPI provides routine vaccination in developing countries. However, vaccines that cannot be given in EPI schedule such as typhoid fever vaccine need alternative venues. In areas where school enrolment is high, schools provide a cost effective opportunity for vaccination. Prior to start of a school-based typhoid vaccination program, interviews were conducted with staff of educational institutions in two townships of Karachi, Pakistan to collect baseline information about the school system and to plan a typhoid vaccination program. Data collection teams administered a structured questionnaire to all schools in the two townships. The administrative staff was requested information on school fee, class enrolment, past history of involvement and willingness of parents to participate in a vaccination campaign. Results A total of 304,836 students were enrolled in 1,096 public, private, and religious schools (Madrasahs of the two towns. Five percent of schools refused to participate in the school census. Twenty-five percent of schools had a total enrolment of less than 100 students whereas 3% had more than 1,000 students. Health education programs were available in less than 8% of public schools, 17% of private schools, and 14% of Madrasahs. One-quarter of public schools, 41% of private schools, and 43% of Madrasahs had previously participated in a school-based vaccination campaign. The most common vaccination campaign in which schools participated was Polio eradication program. Cost of the vaccine, side effects, and parents' lack of information were highlighted as important limiting factors by school administration for school-based immunization programs. Permission from parents, appropriateness of vaccine-related information, and involvement of teachers were considered as important factors to improve participation. Conclusions Health

Efficacy of a non-updated, Matrix-C-based equine influenza subunit-tetanus vaccine following Florida sublineage clade 2 challenge.

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Pouwels, H G W; Van de Zande, S M A; Horspool, L J I; Hoeijmakers, M J H

2014-06-21

Assessing the ability of current equine influenza vaccines to provide cross-protection against emerging strains is important. Horses not vaccinated previously and seronegative for equine influenza based on haemagglutination inhibition (HI) assay were assigned at random to vaccinated (n=7) or non-vaccinated (control, n=5) groups. Vaccination was performed twice four weeks apart with a 1 ml influenza subunit (A/eq/Prague/1/56, A/eq/Newmarket/1/93, A/eq/Newmarket/2/93), tetanus toxoid vaccine with Matrix-C adjuvant (EquilisPrequenza Te). All the horses were challenged individually by aerosol with A/eq/Richmond/1/07 three weeks after the second vaccination. Rectal temperature, clinical signs, serology and virus excretion were monitored for 14 days after challenge. There was no pain at the injection site or increases in rectal temperature following vaccination. Increases in rectal temperature and characteristic clinical signs were recorded in the control horses. Clinical signs were minimal in vaccinated horses. Clinical (P=0.0345) and total clinical scores (P=0.0180) were significantly lower in the vaccinated than in the control horses. Vaccination had a significant effect on indicators of viraemia - the extent (P=0.0006) and duration (P=horse was positive or negative for virus excretion during the study. Further research is needed to fully understand the specific properties of this vaccine that may contribute to its cross-protective capacity. British Veterinary Association.

Vaccines in a hurry.

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Søborg, Christian; Mølbak, Kåre; Doherty, T Mark; Ulleryd, Peter; Brooks, Tim; Coenen, Claudine; van der Zeijst, Ben

2009-05-26

Preparing populations for health threats, including threats from new or re-emerging infectious diseases is recognised as an important public health priority. The development, production and application of emergency vaccinations are the important measures against such threats. Vaccines are cost-effective tools to prevent disease, and emergency vaccines may be the only means to prevent a true disaster for global society in the event of a new pandemic with potential to cause morbidity and mortality comparable to the Spanish flu, the polio epidemics in the 1950s, or the SARS outbreak in 2003 if its spread had not been contained in time. Given the early recognition of a new threat, and given the advances of biotechnology, vaccinology and information systems, it is not an unrealistic goal to have promising prototype vaccine candidates available in a short time span following the identification of a new infectious agent; this is based on the assumption that the emerging infection is followed by natural immunity. However, major bottlenecks for the deployment of emergency vaccine are lack of established systems for fast-track regulatory approval of such candidates and limited international vaccine production capacity. In the present discussion paper, we propose mechanisms to facilitate development of emergency vaccines in Europe by focusing on public-private scientific partnerships, fast-track approval of emergency vaccine by regulatory agencies and proposing incentives for emergency vaccine production in private vaccine companies.

Vaccines today, vaccines tomorrow: a perspective.

Science.gov (United States)

Loucq, Christian

2013-01-01

Vaccines are considered as one of the major contributions of the 20th century and one of the most cost effective public health interventions. The International Vaccine Institute has as a mission to discover, develop and deliver new and improved vaccines against infectious diseases that affects developing nations. If Louis Pasteur is known across the globe, vaccinologists like Maurice Hilleman, Jonas Salk and Charles Mérieux are known among experts only despite their contribution to global health. Thanks to a vaccine, smallpox has been eradicated, polio has nearly disappeared, Haemophilus influenzae B, measles and more recently meningitis A are controlled in many countries. While a malaria vaccine is undergoing phase 3, International Vaccine Institute, in collaboration with an Indian manufacturer has brought an oral inactivated cholera vaccine to pre-qualification. The field of vaccinology has undergone major changes thanks to philanthropists such as Bill and Melinda Gates, initiatives like the Decade of Vaccines and public private partnerships. Current researches on vaccines have more challenging targets like the dengue viruses, malaria, human immunodeficiency virus, the respiratory syncytial virus and nosocomial diseases. Exciting research is taking place on new adjuvants, nanoparticles, virus like particles and new route of administration. An overcrowded infant immunization program, anti-vaccine groups, immunizing a growing number of elderlies and delivering vaccines to difficult places are among challenges faced by vaccinologists and global health experts.

The Ontology of Vaccine Adverse Events (OVAE) and its usage in representing and analyzing adverse events associated with US-licensed human vaccines.

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Marcos, Erica; Zhao, Bin; He, Yongqun

2013-11-26

Licensed human vaccines can induce various adverse events (AE) in vaccinated patients. Due to the involvement of the whole immune system and complex immunological reactions after vaccination, it is difficult to identify the relations among vaccines, adverse events, and human populations in different age groups. Many known vaccine adverse events (VAEs) have been recorded in the package inserts of US-licensed commercial vaccine products. To better represent and analyze VAEs, we developed the Ontology of Vaccine Adverse Events (OVAE) as an extension of the Ontology of Adverse Events (OAE) and the Vaccine Ontology (VO). Like OAE and VO, OVAE is aligned with the Basic Formal Ontology (BFO). The commercial vaccines and adverse events in OVAE are imported from VO and OAE, respectively. A new population term 'human vaccinee population' is generated and used to define VAE occurrence. An OVAE design pattern is developed to link vaccine, adverse event, vaccinee population, age range, and VAE occurrence. OVAE has been used to represent and classify the adverse events recorded in package insert documents of commercial vaccines licensed by the USA Food and Drug Administration (FDA). OVAE currently includes over 1,300 terms, including 87 distinct types of VAEs associated with 63 human vaccines licensed in the USA. For each vaccine, occurrence rates for every VAE in different age groups have been logically represented in OVAE. SPARQL scripts were developed to query and analyze the OVAE knowledge base data. To demonstrate the usage of OVAE, the top 10 vaccines accompanying with the highest numbers of VAEs and the top 10 VAEs most frequently observed among vaccines were identified and analyzed. Asserted and inferred ontology hierarchies classify VAEs in different levels of AE groups. Different VAE occurrences in different age groups were also analyzed. The ontology-based data representation and integration using the FDA-approved information from the vaccine package insert documents

Changes in cytokine and biomarker blood levels in patients with colorectal cancer during dendritic cell-based vaccination

DEFF Research Database (Denmark)

Burgdorf, Stefan K; Claesson, Mogens Helweg; Nielsen, Hans J

2009-01-01

Introduction. Immunotherapy based on dendritic cell vaccination has exciting perspectives for treatment of cancer. In order to clarify immunological mechanisms during vaccination it is essential with intensive monitoring of the responses. This may lead to optimization of treatment and prediction...... of responding patients. The aim of this study was to evaluate cytokine and biomarker responses in patients with colorectal cancer treated with a cancer vaccine based on dendritic cells pulsed with an allogeneic melanoma cell lysate. Material and methods. Plasma and serum samples were collected prior...... disease showed increasing levels of plasma GM-CSF, TNF-alpha, IFN-gamma, IL-2, and IL-5. Patients with progressive disease showed significant increase in CEA and TIMP-1 levels, while patients with stable disease showed relatively unaltered levels. Conclusion. The increased levels of key pro...

DNA vaccines for aquacultured fish

DEFF Research Database (Denmark)

Lorenzen, Niels; LaPatra, S.E.

2005-01-01

of licensing and public acceptance of the technology. The potential benefits of DNA vaccines for farmed fish include improved animal welfare, reduced environmental impacts of aquaculture activities, increased food quality and quantity, and more sustainable production. Testing under commercial production......Deoxyribonucleic acid (DNA) vaccination is based on the administration of the gene encoding the vaccine antigen, rather than the antigen itself. Subsequent expression of the antigen by cells in the vaccinated hosts triggers the host immune system. Among the many experimental DNA vaccines tested...... in various animal species as well as in humans, the vaccines against rhabdovirus diseases in fish have given some of the most promising results. A single intramuscular (IM) injection of microgram amounts of DNA induces rapid and long-lasting protection in farmed salmonids against economically important...

Costs of delivering human papillomavirus vaccination to schoolgirls in Mwanza Region, Tanzania

Science.gov (United States)

2012-01-01

Background Cervical cancer is the leading cause of female cancer-related deaths in Tanzania. Vaccination against human papillomavirus (HPV) offers a new opportunity to control this disease. This study aimed to estimate the costs of a school-based HPV vaccination project in three districts in Mwanza Region (NCT ID: NCT01173900), Tanzania and to model incremental scaled-up costs of a regional vaccination program. Methods We first conducted a top-down cost analysis of the vaccination project, comparing observed costs of age-based (girls born in 1998) and class-based (class 6) vaccine delivery in a total of 134 primary schools. Based on the observed project costs, we then modeled incremental costs of a scaled-up vaccination program for Mwanza Region from the perspective of the Tanzanian government, assuming that HPV vaccines would be delivered through the Expanded Programme on Immunization (EPI). Results Total economic project costs for delivering 3 doses of HPV vaccine to 4,211 girls were estimated at about US$349,400 (including a vaccine price of US$5 per dose). Costs per fully-immunized girl were lower for class-based delivery than for age-based delivery. Incremental economic scaled-up costs for class-based vaccination of 50,290 girls in Mwanza Region were estimated at US$1.3 million. Economic scaled-up costs per fully-immunized girl were US$26.41, including HPV vaccine at US$5 per dose. Excluding vaccine costs, vaccine could be delivered at an incremental economic cost of US$3.09 per dose and US$9.76 per fully-immunized girl. Financial scaled-up costs, excluding costs of the vaccine and salaries of existing staff were estimated at US$1.73 per dose. Conclusions Project costs of class-based vaccination were found to be below those of age-based vaccination because of more eligible girls being identified and higher vaccine uptake. We estimate that vaccine can be delivered at costs that would make HPV vaccination a very cost-effective intervention. Potentially

A new intranasal influenza vaccine based on a novel polycationic lipid-ceramide carbamoyl-spermine (CCS). II. Studies in mice and ferrets and mechanism of adjuvanticity.

Science.gov (United States)

Even-Or, Orli; Joseph, Aviva; Itskovitz-Cooper, Noga; Samira, Sarit; Rochlin, Eli; Eliyahu, Hagit; Goldwaser, Itzik; Balasingam, Shobana; Mann, Alex J; Lambkin-Williams, Rob; Kedar, Eli; Barenholz, Yechezkel

2011-03-16

We recently showed that lipid assemblies comprised of a novel polycationic sphingolipid (ceramide carbamoyl-spermine, CCS) are an effective adjuvant/carrier when complexed with cholesterol (CCS/C) for influenza and other vaccines administered parenterally and intranasally (i.n.) in mice. Here we expand these studies to ferrets, an established model of influenza infection. We also address the question of why the CCS/C-based liposomal vaccine (also known as VaxiSome™) in mice is superior to vaccines based on liposomes of other lipid compositions (neutral, anionic or cationic). Ferrets immunized i.n. with CCS/C-influenza vaccine produced significantly higher hemagglutination inhibition (HI) antibody titers compared to ferrets immunized intramuscularly with the unadjuvanted influenza vaccine, indicating that the CCS/C-based vaccine is very immunogenic. Furthermore, the i.n. adjuvanted vaccine was shown to significantly reduce the severity of influenza virus infection in ferrets following homologous viral challenge as determined by weight loss, temperature rise and viral titer. No adverse reactions were observed. Pharmacokinetic and biodistribution studies following i.n. administration in mice of CCS/C-based vaccine showed that both the lipids and antigens are retained in the nose and lung for at least 24h, and it appears that this retention correlates with the superior immunogenicity elicited by the adjuvanted vaccine formulation. The CCS lipid also increases production of cytokines (mainly IFN gamma, IL-2 and IL-12) and co-stimulatory molecules' expression, which might further explain the robust adjuvantation of this liposome-based vaccine. Copyright © 2011 Elsevier Ltd. All rights reserved.

ADE and dengue vaccination.

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Martínez-Vega, Ruth Aralí; Carrasquila, Gabriel; Luna, Expedito; Ramos-Castañeda, José

2017-07-13

The vaccine against Dengue virus (DENV), Dengvaxia® (CYD), produced by Sanofi-Pasteur, has been registered by several national regulatory agencies; nevertheless, the performance and security of this vaccine have been challenged in a series of recent papers. In this work, we intend to contribute to the debate by analyzing the concept of an enhancing vaccine, presenting objections to the epidemiological model base of the concept and, likewise, presenting data that contradict that concept. Copyright © 2017 Elsevier Ltd. All rights reserved.

Novel GMO-Based Vaccines against Tuberculosis: State of the Art and Biosafety Considerations

Science.gov (United States)

Leunda, Amaya; Baldo, Aline; Goossens, Martine; Huygen, Kris; Herman, Philippe; Romano, Marta

2014-01-01

Novel efficient vaccines are needed to control tuberculosis (TB), a major cause of morbidity and mortality worldwide. Several TB vaccine candidates are currently in clinical and preclinical development. They fall into two categories, the one of candidates designed as a replacement of the Bacille Calmette Guérin (BCG) to be administered to infants and the one of sub-unit vaccines designed as booster vaccines. The latter are designed as vaccines that will be administered to individuals already vaccinated with BCG (or in the future with a BCG replacement vaccine). In this review we provide up to date information on novel tuberculosis (TB) vaccines in development focusing on the risk assessment of candidates composed of genetically modified organisms (GMO) which are currently evaluated in clinical trials. Indeed, these vaccines administered to volunteers raise biosafety concerns with respect to human health and the environment that need to be assessed and managed. PMID:26344627

Novel GMO-Based Vaccines against Tuberculosis: State of the Art and Biosafety Considerations

Directory of Open Access Journals (Sweden)

Amaya Leunda

2014-06-01

Full Text Available Novel efficient vaccines are needed to control tuberculosis (TB, a major cause of morbidity and mortality worldwide. Several TB vaccine candidates are currently in clinical and preclinical development. They fall into two categories, the one of candidates designed as a replacement of the Bacille Calmette Guérin (BCG to be administered to infants and the one of sub-unit vaccines designed as booster vaccines. The latter are designed as vaccines that will be administered to individuals already vaccinated with BCG (or in the future with a BCG replacement vaccine. In this review we provide up to date information on novel tuberculosis (TB vaccines in development focusing on the risk assessment of candidates composed of genetically modified organisms (GMO which are currently evaluated in clinical trials. Indeed, these vaccines administered to volunteers raise biosafety concerns with respect to human health and the environment that need to be assessed and managed.

Safety of human papillomavirus vaccines: a review.

Science.gov (United States)

Stillo, Michela; Carrillo Santisteve, Paloma; Lopalco, Pier Luigi

2015-05-01

Between 2006 and 2009, two different human papillomavirus virus (HPV) vaccines were licensed for use: a quadrivalent (qHPVv) and a bivalent (bHPVv) vaccine. Since 2008, HPV vaccination programmes have been implemented in the majority of the industrialized countries. Since 2013, HPV vaccination has been part of the national programs of 66 countries including almost all countries in North America and Western Europe. Despite all the efforts made by individual countries, coverage rates are lower than expected. Vaccine safety represents one of the main concerns associated with the lack of acceptance of HPV vaccination both in the European Union/European Economic Area and elsewhere. Safety data published on bivalent and quadrivalent HPV vaccines, both in pre-licensure and post-licensure phase, are reviewed. Based on the latest scientific evidence, both HPV vaccines seem to be safe. Nevertheless, public concern and rumors about adverse events (AE) represent an important barrier to overcome in order to increase vaccine coverage. Passive surveillance of AEs is an important tool for detecting safety signals, but it should be complemented by activities aimed at assessing the real cause of all suspect AEs. Improved vaccine safety surveillance is the first step for effective communication based on scientific evidence.

Genetically-barcoded SIV facilitates enumeration of rebound variants and estimation of reactivation rates in nonhuman primates following interruption of suppressive antiretroviral therapy.

Directory of Open Access Journals (Sweden)

Christine M Fennessey

2017-05-01

Full Text Available HIV and SIV infection dynamics are commonly investigated by measuring plasma viral loads. However, this total viral load value represents the sum of many individual infection events, which are difficult to independently track using conventional sequencing approaches. To overcome this challenge, we generated a genetically tagged virus stock (SIVmac239M with a 34-base genetic barcode inserted between the vpx and vpr accessory genes of the infectious molecular clone SIVmac239. Next-generation sequencing of the virus stock identified at least 9,336 individual barcodes, or clonotypes, with an average genetic distance of 7 bases between any two barcodes. In vitro infection of rhesus CD4+ T cells and in vivo infection of rhesus macaques revealed levels of viral replication of SIVmac239M comparable to parental SIVmac239. After intravenous inoculation of 2.2x105 infectious units of SIVmac239M, an average of 1,247 barcodes were identified during acute infection in 26 infected rhesus macaques. Of the barcodes identified in the stock, at least 85.6% actively replicated in at least one animal, and on average each barcode was found in 5 monkeys. Four infected animals were treated with combination antiretroviral therapy (cART for 82 days starting on day 6 post-infection (study 1. Plasma viremia was reduced from >106 to <15 vRNA copies/mL by the time treatment was interrupted. Virus rapidly rebounded following treatment interruption and between 87 and 136 distinct clonotypes were detected in plasma at peak rebound viremia. This study confirmed that SIVmac239M viremia could be successfully curtailed with cART, and that upon cART discontinuation, rebounding viral variants could be identified and quantified. An additional 6 animals infected with SIVmac239M were treated with cART beginning on day 4 post-infection for 305, 374, or 482 days (study 2. Upon treatment interruption, between 4 and 8 distinct viral clonotypes were detected in each animal at peak rebound

Oral Cholera Vaccination Delivery Cost in Low- and Middle-Income Countries: An Analysis Based on Systematic Review.

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Mogasale, Vittal; Ramani, Enusa; Wee, Hyeseung; Kim, Jerome H

2016-12-01

Use of the oral cholera vaccine (OCV) is a vital short-term strategy to control cholera in endemic areas with poor water and sanitation infrastructure. Identifying, estimating, and categorizing the delivery costs of OCV campaigns are useful in analyzing cost-effectiveness, understanding vaccine affordability, and in planning and decision making by program managers and policy makers. To review and re-estimate oral cholera vaccination program costs and propose a new standardized categorization that can help in collation, analysis, and comparison of delivery costs across countries. Peer reviewed publications listed in PubMed database, Google Scholar and World Health Organization (WHO) websites and unpublished data from organizations involved in oral cholera vaccination. The publications and reports containing oral cholera vaccination delivery costs, conducted in low- and middle-income countries based on World Bank Classification. Limits are humans and publication date before December 31st, 2014. No participants are involved, only costs are collected. Oral cholera vaccination and cost estimation. A systematic review was conducted using pre-defined inclusion and exclusion criteria. Cost items were categorized into four main cost groups: vaccination program preparation, vaccine administration, adverse events following immunization and vaccine procurement; the first three groups constituting the vaccine delivery costs. The costs were re-estimated in 2014 US dollars (US$) and in international dollar (I$). Ten studies were identified and included in the analysis. The vaccine delivery costs ranged from US$0.36 to US$ 6.32 (in US$2014) which was equivalent to I$ 0.99 to I$ 16.81 (in I$2014). The vaccine procurement costs ranged from US$ 0.29 to US$ 29.70 (in US$2014), which was equivalent to I$ 0.72 to I$ 78.96 (in I$2014). The delivery costs in routine immunization systems were lowest from US$ 0.36 (in US$2014) equivalent to I$ 0.99 (in I$2014). The reported cost categories

Antibody Persistence in Adults Two Years after Vaccination with an H1N1 2009 Pandemic Influenza Virus-Like Particle Vaccine.

Directory of Open Access Journals (Sweden)

Nuriban Valero-Pacheco

Full Text Available The influenza virus is a human pathogen that causes epidemics every year, as well as potential pandemic outbreaks, as occurred in 2009. Vaccination has proven to be sufficient in the prevention and containment of viral spreading. In addition to the current egg-based vaccines, new and promising vaccine platforms, such as cell culture-derived vaccines that include virus-like particles (VLPs, have been developed. VLPs have been shown to be both safe and immunogenic against influenza infections. Although antibody persistence has been studied in traditional egg-based influenza vaccines, studies on antibody response durations induced by VLP influenza vaccines in humans are scarce. Here, we show that subjects vaccinated with an insect cell-derived VLP vaccine, in the midst of the 2009 H1N1 influenza pandemic outbreak in Mexico City, showed antibody persistence up to 24 months post-vaccination. Additionally, we found that subjects that reported being revaccinated with a subsequent inactivated influenza virus vaccine showed higher antibody titres to the pandemic influenza virus than those who were not revaccinated. These findings provide insights into the duration of the antibody responses elicited by an insect cell-derived pandemic influenza VLP vaccine and the possible effects of subsequent influenza vaccination on antibody persistence induced by this VLP vaccine in humans.

Progress towards development of an HIV vaccine: report of the AIDS Vaccine 2009 Conference.

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Ross, Anna Laura; Bråve, Andreas; Scarlatti, Gabriella; Manrique, Amapola; Buonaguro, Luigi

2010-05-01

The search for an HIV/AIDS vaccine is steadily moving ahead, generating and validating new concepts in terms of novel vectors for antigen delivery and presentation, new vaccine and adjuvant strategies, alternative approaches to design HIV-1 antigens for eliciting protective cross-neutralising antibodies, and identification of key mechanisms in HIV infection and modulation of the immune system. All these different perspectives are contributing to the unprecedented challenge of developing a protective HIV-1 vaccine. The high scientific value of this massive effort is its great impact on vaccinology as a whole, providing invaluable scientific information for the current and future development of new preventive vaccine as well as therapeutic knowledge-based infectious-disease and cancer vaccines. Copyright 2010 Elsevier Ltd. All rights reserved.

Cost-effectiveness of routine varicella vaccination using the measles, mumps, rubella and varicella vaccine in France: an economic analysis based on a dynamic transmission model for varicella and herpes zoster.

Science.gov (United States)

Littlewood, Kavi J; Ouwens, Mario J N M; Sauboin, Christophe; Tehard, Bertrand; Alain, Sophie; Denis, François

2015-04-01

Each year in France, varicella and zoster affect large numbers of children and adults, resulting in medical visits, hospitalizations for varicella- and zoster-related complications, and societal costs. Disease prevention by varicella vaccination is feasible, wherein a plausible option involves replacing the combined measles, mumps, and rubella (MMR) vaccine with the combined MMR and varicella (MMRV) vaccine. This study aimed to: (1) assess the cost-effectiveness of adding routine varicella vaccination through MMRV, using different vaccination strategies in France; and (2) address key uncertainties, such as the economic consequences of breakthrough varicella cases, the waning of vaccine-conferred protection, vaccination coverage, and indirect costs. Based on the outputs of a dynamic transmission model that used data on epidemiology and costs from France, a cost-effectiveness model was built. A conservative approach was taken regarding the impact of varicella vaccination on zoster incidence by assuming the validity of the hypothesis of an age-specific boosting of immunity against varicella. The model determined that routine MMRV vaccination is expected to be a cost-effective option, considering a cost-effectiveness threshold of €20,000 per quality-adjusted life-year saved; routine vaccination was cost-saving from the societal perspective. Results were driven by a large decrease in varicella incidence despite a temporary initial increase in the number of zoster cases due to the assumption of exogenous boosting. In the scenario analyses, despite moderate changes in assumptions about incidence and costs, varicella vaccination remained a cost-effective option for France. Routine vaccination with MMRV was associated with high gains in quality-adjusted life-years, substantial reduction in the occurrences of varicella- and zoster-related complications, and few deaths due to varicella. Routine MMRV vaccination is also expected to provide reductions in costs related to

Epitope-based peptide vaccine design and target site depiction against Ebola viruses: an immunoinformatics study.

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Khan, M A; Hossain, M U; Rakib-Uz-Zaman, S M; Morshed, M N

2015-07-01

Ebola viruses (EBOVs) have been identified as an emerging threat in recent year as it causes severe haemorrhagic fever in human. Epitope-based vaccine design for EBOVs remains a top priority because a mere progress has been made in this regard. Another reason is the lack of antiviral drug and licensed vaccine although there is a severe outbreak in Central Africa. In this study, we aimed to design an epitope-based vaccine that can trigger a significant immune response as well as to prognosticate inhibitor that can bind with potential drug target sites using various immunoinformatics and docking simulation tools. The capacity to induce both humoral and cell-mediated immunity by T cell and B cell was checked for the selected protein. The peptide region spanning 9 amino acids from 42 to 50 and the sequence TLASIGTAF were found as the most potential B and T cell epitopes, respectively. This peptide could interact with 12 HLAs and showed high population coverage up to 80.99%. Using molecular docking, the epitope was further appraised for binding against HLA molecules to verify the binding cleft interaction. In addition with this, the allergenicity of the epitopes was also evaluated. In the post-therapeutic strategy, docking study of predicted 3D structure identified suitable therapeutic inhibitor against targeted protein. However, this computational epitope-based peptide vaccine designing and target site prediction against EBOVs open up a new horizon which may be the prospective way in Ebola viruses research; the results require validation by in vitro and in vivo experiments. © 2015 John Wiley & Sons Ltd.

Engineering Enhanced Vaccine Cell Lines To Eradicate Vaccine-Preventable Diseases: the Polio End Game.

Science.gov (United States)

van der Sanden, Sabine M G; Wu, Weilin; Dybdahl-Sissoko, Naomi; Weldon, William C; Brooks, Paula; O'Donnell, Jason; Jones, Les P; Brown, Cedric; Tompkins, S Mark; Oberste, M Steven; Karpilow, Jon; Tripp, Ralph A

2016-02-15

Vaccine manufacturing costs prevent a significant portion of the world's population from accessing protection from vaccine-preventable diseases. To enhance vaccine production at reduced costs, a genome-wide RNA interference (RNAi) screen was performed to identify gene knockdown events that enhanced poliovirus replication. Primary screen hits were validated in a Vero vaccine manufacturing cell line using attenuated and wild-type poliovirus strains. Multiple single and dual gene silencing events increased poliovirus titers >20-fold and >50-fold, respectively. Host gene knockdown events did not affect virus antigenicity, and clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9-mediated knockout of the top candidates dramatically improved viral vaccine strain production. Interestingly, silencing of several genes that enhanced poliovirus replication also enhanced replication of enterovirus 71, a clinically relevant virus to which vaccines are being targeted. The discovery that host gene modulation can markedly increase virus vaccine production dramatically alters mammalian cell-based vaccine manufacturing possibilities and should facilitate polio eradication using the inactivated poliovirus vaccine. Using a genome-wide RNAi screen, a collection of host virus resistance genes was identified that, upon silencing, increased poliovirus and enterovirus 71 production by from 10-fold to >50-fold in a Vero vaccine manufacturing cell line. This report provides novel insights into enterovirus-host interactions and describes an approach to developing the next generation of vaccine manufacturing through engineered vaccine cell lines. The results show that specific gene silencing and knockout events can enhance viral titers of both attenuated (Sabin strain) and wild-type polioviruses, a finding that should greatly facilitate global implementation of inactivated polio vaccine as well as further reduce costs for live-attenuated oral polio vaccines. This work

Clinical development of a VAR2CSA-based placental malaria vaccine PAMVAC

DEFF Research Database (Denmark)

Gbédandé, Komi; Fievet, Nadine; Viwami, Firmine

2017-01-01

Background  The antigen VAR2CSA plays a pivotal role in the pathophysiology of pregnancy-associated malaria (PAM) caused by Plasmodium falciparum. A VAR2CSA-based vaccine candidate, PAMVAC, is under development by an EU-funded multi-country consortium (PlacMalVac project). As part of PAMVAC...

A population-based study of measles, mumps and rubella vaccination and autism

DEFF Research Database (Denmark)

Madsen, Kreesten Meldgaard; Hviid, Anders; Vestergaard, Mogens

2002-01-01

Background It has been suggested that vaccination against measles, mumps, and rubella (MMR) is a cause of autism. Methods We conducted a retrospective cohort study of all children born in Denmark from January 1991 through December 1998. The cohort was selected on the basis of data from the Danish...... Civil Registration System, which assigns a unique identification number to every live-born infant and new resident in Denmark. MMR-vaccination status was obtained from the Danish National Board of Health. Information on the children’s autism status was obtained from the Danish Psychiatric Central...... the age at the time of vaccination, the time since vaccination, or the date of vaccination and the development of autistic disorder. Conclusions This study provides strong evidence against the hypothesis that MMR vaccination causes autism....

A population-based study of measles, mumps and rubella vaccination and autism

DEFF Research Database (Denmark)

Madsen, Kreesten Meldgaard; Hviid, Anders; Vestergaard, Mogens

2002-01-01

Background It has been suggested that vaccination against measles, mumps, and rubella (MMR) is a cause of autism. Methods We conducted a retrospective cohort study of all children born in Denmark from January 1991 through December 1998. The cohort was selected on the basis of data from the Danish...... the age at the time of vaccination, the time since vaccination, or the date of vaccination and the development of autistic disorder. Conclusions This study provides strong evidence against the hypothesis that MMR vaccination causes autism....... Civil Registration System, which assigns a unique identification number to every live-born infant and new resident in Denmark. MMR-vaccination status was obtained from the Danish National Board of Health. Information on the children’s autism status was obtained from the Danish Psychiatric Central...

Adenovirus-vectored Ebola vaccines.

Science.gov (United States)

Gilbert, Sarah C

2015-01-01

The 2014 outbreak of Ebola virus disease in West Africa has highlighted the need for the availability of effective vaccines against outbreak pathogens that are suitable for use in frontline workers who risk their own health in the course of caring for those with the disease, and also for members of the community in the affected area. Along with effective contact tracing and quarantine, use of a vaccine as soon as an outbreak is identified could greatly facilitate rapid control and prevent the outbreak from spreading. This review describes the progress that has been made in producing and testing adenovirus-based Ebola vaccines in both pre-clinical and clinical studies, and considers the likely future use of these vaccines.

Parental Vaccine Acceptance: A Logistic Regression Model Using Previsit Decisions.

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Lee, Sara; Riley-Behringer, Maureen; Rose, Jeanmarie C; Meropol, Sharon B; Lazebnik, Rina

2017-07-01

This study explores how parents' intentions regarding vaccination prior to their children's visit were associated with actual vaccine acceptance. A convenience sample of parents accompanying 6-week-old to 17-year-old children completed a written survey at 2 pediatric practices. Using hierarchical logistic regression, for hospital-based participants (n = 216), vaccine refusal history ( P < .01) and vaccine decision made before the visit ( P < .05) explained 87% of vaccine refusals. In community-based participants (n = 100), vaccine refusal history ( P < .01) explained 81% of refusals. Over 1 in 5 parents changed their minds about vaccination during the visit. Thirty parents who were previous vaccine refusers accepted current vaccines, and 37 who had intended not to vaccinate choose vaccination. Twenty-nine parents without a refusal history declined vaccines, and 32 who did not intend to refuse before the visit declined vaccination. Future research should identify key factors to nudge parent decision making in favor of vaccination.

A novel cancer vaccine strategy based on HLA-A*0201 matched allogeneic plasmacytoid dendritic cells.

Directory of Open Access Journals (Sweden)

Caroline Aspord

Full Text Available BACKGROUND: The development of effective cancer vaccines still remains a challenge. Despite the crucial role of plasmacytoid dendritic cells (pDCs in anti-tumor responses, their therapeutic potential has not yet been worked out. We explored the relevance of HLA-A*0201 matched allogeneic pDCs as vectors for immunotherapy. METHODS AND FINDINGS: Stimulation of PBMC from HLA-A*0201(+ donors by HLA-A*0201 matched allogeneic pDCs pulsed with tumor-derived peptides triggered high levels of antigen-specific and functional cytotoxic T cell responses (up to 98% tetramer(+ CD8 T cells. The pDC vaccine demonstrated strong anti-tumor therapeutic in vivo efficacy as shown by the inhibition of tumor growth in a humanized mouse model. It also elicited highly functional tumor-specific T cells ex-vivo from PBMC and TIL of stage I-IV melanoma patients. Responses against MelA, GP100, tyrosinase and MAGE-3 antigens reached tetramer levels up to 62%, 24%, 85% and 4.3% respectively. pDC vaccine-primed T cells specifically killed patients' own autologous melanoma tumor cells. This semi-allogeneic pDC vaccine was more effective than conventional myeloid DC-based vaccines. Furthermore, the pDC vaccine design endows it with a strong potential for clinical application in cancer treatment. CONCLUSIONS: These findings highlight HLA-A*0201 matched allogeneic pDCs as potent inducers of tumor immunity and provide a promising immunotherapeutic strategy to fight cancer.

Single-cycle adenovirus vectors in the current vaccine landscape.

Science.gov (United States)

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.