Table of Contents

Volume 2, Issue 2

  March/April 2006

  Pages 45 - 85

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 Issue Catalogue (MARC XML)

REVIEW

Open Access Article

Preclinical and Clinical Safety Studies on DNA Vaccines

Johanna A.C. Schalk, Frits R. Mooi, Guy A.M. Berbers, Leon A.G.J.M. van Aerts, Hans Ovelgönne and Tjeerd G. Kimman
Pages 45 - 53
http://dx.doi.org/10.4161/hv.2.2.2620
Abstract | PDF

DNA vaccines are based on the transfer of genetic material, encoding an antigen, to the cells of the vaccine recipient. Despite high expectations of DNA vaccines as a result of promising preclinical data their clinical utility remains unproven. However, much data is gathered in preclinical and clinical studies about the safety of DNA vaccines. Here we review current knowledge about the safety of DNA vaccines. Safety concerns of DNA vaccines relate to genetic, immunologic, toxic, and environmental effects. In this review we provide an overview of findings related to the safety of DNA vaccines, obtained so far. We conclude that the potential risks of DNA vaccines are minimal. However, their safety issues may differ case-by-case, and they should be treated accordingly.




RESEARCH PAPERS

Open Access Article

Military Hospitalizations Among Deployed US Service Members Following Anthrax Vaccination, 1998–2001

Timothy Steven Wells, Paul A. Sato, Tyler Clain Smith, Linda Zhenling Wang, Robert John Reed and Margaret Angela Kappel Ryan
Pages 54 - 59
http://dx.doi.org/10.4161/hv.2.2.2589
Abstract | PDF

Safety concerns have confronted the Department of Defense Anthrax Vaccine Immunization Program since inception in 1998. To determine if anthrax vaccination was associated with an increased risk of hospitalization, a historical cohort study utilizing pre- and post-anthrax-vaccination hospitalizations was undertaken and analyzed with Cox proportional hazards models. The study population consisted of 170,723 active duty US service members who were anthrax-vaccinated and deployed during the time period January 1, 1998 to December 31, 2001. Study outcomes included hospitalizations due to any-cause, 14 broad International Classification of Diseases diagnostic categories, autoimmune organ specific and organ non-specific hospitalizations, and asthma. After adjustment, anthrax vaccination was associated with significantly fewer hospitalizations for any-cause, diseases of the blood and blood forming organs, and diseases of the gastrointestinal and respiratory systems. Comparing anthrax postvaccination hospitalization experience with the prevaccination period resulted in no significant increased hazard for any of the hospitalization outcomes studied. Although there was no apparent increase in risk of morbidity in this study population, the relationship between anthrax vaccine and deployment on health outcomes among US service members needs further study.

Open Access Article

Live Attenuated Chimeric Yellow Fever Dengue Type 2 (ChimeriVax™-DEN2) Vaccine: Phase I Clinical Trial for Safety and Immunogenicity: Effect of Yellow Fever Pre-immunity in Induction of Cross Neutralizing Antibody Responses to All

Farshad Guirakhoo, Scott Kitchener, Dennis Morrison, Remi Forrat, Karen McCarthy, Richard Nichols, Sutee Yoksan, Xiaochu Duan, Thomas H. Ermak, Niranjan Kanesa-Thasan, Philip Bedford, Jean Lang, Marie-Jose Quentin-Millet and Thomas P. Monath
Pages 60 - 67
http://dx.doi.org/10.4161/hv.2.2.2555
Abstract | PDF

A randomized double-blind Phase I Trial was conducted to evaluate safety, tolerability, and immunogenicity of a yellow fever (YF)-dengue 2 (DEN2) chimera (ChimeriVax™-DEN2) in comparison to that of YF vaccine (YF-VAX®). Forty-two healthy YF naïve adults randomly received a single dose of either ChimeriVax™-DEN2 (high dose, 5 log plaque forming units [PFU] or low dose, 3 log PFU) or YF-VAXâ by the subcutaneous route (SC). To determine the effect of YF pre-immunity on the ChimeriVaxTM-DEN2 vaccine, 14 subjects previously vaccinated against YF received a high dose of ChimeriVax™-DEN2 as an open-label vaccine. Most adverse events were similar to YF-VAX® and of mild to moderate intensity, with no serious side-effects. One hundred percent and 92.3% of YF naïve subjects inoculated with 5.0 and 3.0 log10 PFU of ChimeriVaxTM-DEN2, respectively, seroconverted to wt DEN2 (strain 16681); 92% of subjects inoculated with YF-VAX® seroconverted to YF 17D virus but none of YF naïve subjects inoculated with ChimeriVax-DEN2 seroconverted to YF 17D virus. Low seroconversion rates to heterologous DEN serotypes 1, 3, and 4 were observed in YF naïve subjects inoculated with either ChimeriVax™-DEN2 or YF-VAX®. In contrast, 100% of YF immune subjects inoculated with ChimeriVax™-DEN2 seroconverted to all 4 DEN serotypes. Surprisingly, levels of neutralizing antibodies to DEN 1, 2, and 3 viruses in YF immune subjects persisted after 1 year. These data demonstrated that 1) the safety and immunogenicity profile of the ChimeriVax™-DEN2 vaccine is consistent with that of YF-VAX®, and 2) pre-immunity to YF virus does not interfere with ChimeriVaxTM-DEN2 immunization, but induces a long lasting and cross neutralizing antibody response to all 4 DEN serotypes. The latter observation can have practical implications toward development of a dengue vaccine.

Open Access Article

Modeling Future Changes to the Meningococcal Serogroup C Conjugate (MCC) Vaccine Program in England and Wales

Caroline L. Trotter, W. John Edmunds, Mary E. Ramsay and Elizabeth Miller
Pages 68 - 73
http://dx.doi.org/10.4161/hv.2.2.2611
Abstract | PDF

The UK meningococcal serogroup C conjugate (MCC) vaccine program has successfully controlled serogroup C disease, due to high vaccine effectiveness and substantial herd immunity. However, children immunised at 2, 3 and 4 months of age receive only short-term direct protection and may be at risk of disease 15 months after vaccination. To investigate this we applied a mathematical model to predict the future epidemiology of serogroup C disease, with and without changes to the immunisation schedule. Only a few cases of serogroup C disease were predicted to occur over the next few years because of persisting herd immunity, even without a change to the vaccine schedule, indicating that urgent schedule changes are not required. The inclusion of a booster dose is likely to improve the impact of the MCC program and reducing the number of doses in infancy will improve cost-effectiveness and create space in the schedule for the addition of other vaccines.

Open Access Article

Association Between Immunogenicity and Adsorption of a Recombinant Streptococcus pneumoniae Vaccine Antigen by an Aluminum Adjuvant

Philip M. Levesque, Kimberly Foster and Uditha de Alwis
Pages 74 - 77
http://dx.doi.org/10.4161/hv.2.2.2645
Abstract | PDF

The impact on immunogenicity of the degree of adsorption of three Streptococcus pneumoniae (Sp) vaccine antigens to aluminum adjuvants was studied. The three antigens evaluated (Sp1, Sp2 and Sp3) were highly adsorbed by aluminum hydroxide adjuvant, but not adsorbed by aluminum phosphate adjuvant. All of the Sp antigens adjuvanted with aluminum hydroxide elicited higher antibody responses in mice than formulations prepared with aluminum phosphate or non-adjuvanted antigen. Varying the percent aluminum-bound Sp antigen in the formulated vaccine affected the observed antibody responses. These observations suggest that the antibody response observed for Sp antigens in this study is stimulated by a depot effect of the antigen bound to an aluminum adjuvant.

Open Access Article

DNA-Based Immunization Breaks Tolerance in a Hepatitis C Virus Transgenic Mouse Model

Jens Encke, Michael Geissler, Wolfgang Stremmel and Jack R. Wands
Pages 78 - 83
http://dx.doi.org/10.4161/hv.2.2.2699
Abstract | PDF

Chronic hepatitis C infection (HCV) is associated with high morbidity and mortality due to limited treatment options. HCV transgenic mice can be used as surrogate model of chronic HCV infection and may therefore be a small animal model for the evaluation of therapeutic vaccination strategies. We immunized transgenic mice expressing HCV structural proteins with an HCV core and a mouse IL-2 expression plasmid to study the cellular and humoral immune responses. DNA-based immunization induced a significant CD4+ T cell proliferative response and a CD8+ cytotoxic T cell response. Only low amounts of anti-HCV core antibodies were detected after genetic immunization. No liver damage was observed in the liver of immunized mice despite low level HCV core transgene expression and the presence of peripheral cellular immunity. These results demonstrate that DNA-based immunization may result in activation of previously tolerant T cells and is therefore a promising approach for treatment of chronic HCV infection.




COMMENTARY

Open Access Article

Rotavirus Vaccines: Round Two

Paul A. Offit
Pages 84 - 85
http://dx.doi.org/10.4161/hv.2.2.2612
Abstract | PDF

No abstract available.