Table of Contents

Volume 1, Issue 4

  July/August 2005

  Pages 131 - 176

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 Issue Catalogue (MARC XML)

REVIEWS

Open Access Article

Group C Meningococcal Polysaccharide-Tetanus Toxoid Conjugate Vaccine: A Meta-Analysis of Immunogenicity, Safety and Posology

Eva Maria Pöllabauer, Robert Petermann and Hartmut J. Ehrlich
Pages 131 - 139
http://dx.doi.org/10.4161/hv.1.4.2018
Abstract | PDF

A conjugate vaccine comprised of de-O-acetylated group C meningococcal polysaccharide coupled to tetanus toxoid (GCMP-TT) has been licensed in 32 countries and incorporated in a comprehensive UK vaccination program. Extensive evidence, forming the subject of this meta-analysis, has rapidly accumulated on the immunogenicity, safety and posology of GCMP-TT as well as its epidemiological impact. GCMP-TT has been shown effective after a single dose in individuals > 12 months of age, and initial posology specified three doses in infants. However, based on a recent clinical trial, posology was reduced to two doses in infants. Pooled protection rate, defined as proportion of subjects with serum bactericidal antibody (SBA) levels 1:8, was 99.4% (CI, 98.2-99.9 %) in 7 clinical trials covering all age groups. Robust responses to GCMP-TT have been demonstrated with respect to SBA, IgG levels and antibody avidity. In post-marketing pharmacosurveillance encompassing > 12 * 106 GCMP-TT doses distributed worldwide, the vaccine has been well tolerated with an incidence rate of 0.01% for all the most commonly encountered types of adverse events. After a catch-up UK vaccination campaign where 5-8 year old children were primarily given GCMP-TT, a 93% decline in meningococcal disease incidence was observed. In view of its immunogenicity, safety and potential suitability for use among infants in reduced dose schedules, GCMP-TT appears to mark a major advance over predecessor polysaccharide vaccines for the prevention of meningococcal C disease.

Open Access Article

Canadian Association for Immunization Research and Evaluation (CAIRE) Guidelines for Industry Sponsored Clinical Trial and Epidemiology Contract Research

Scott A. Halperin and 22 others
Pages 140 - 142
http://dx.doi.org/10.4161/hv.1.4.1971
Abstract | PDF

In response to concerns about interactions of academic and public health investigators with industry, the Canadian Association for Immunization Research and Evaluation (CAIRE), in collaboration with six major vaccine manufacturers, developed guidelines for participation in industry-sponsored clinical trial and epidemiology contract research within Canada. Topics addressed include definition of investigators, data ownership, protocol development, data management, data analysis, producing a study report and publication of the results of the study.

Open Access Article

The Prospect of Vaccination to Prevent Type 1 Diabetes

Leonard C. Harrison
Pages 143 - 150
http://dx.doi.org/10.4161/hv.1.4.1923
Abstract | PDF

Type 1 diabetes (T1D) is an autoimmune disease in which genes and environment contribute to cell-mediated immune destruction of insulin-producing ? cells in the islets of the pancreas. An understanding of pathogenetic mechanisms paves the way for vaccination strategies to prevent T1D. Primary prevention by traditional ‘positive’ vaccination awaits clear evidence of a the role for infectious agents in triggering the disease process. Following initiation of disease, at-risk individuals with underlying islet inflammation can be identified by the presence of circulating autoantibodies to islet antigens. This pre-clinical phase of T1D, before insulin deficiency leads to symptoms of hyperglycemia, provides a window for secondary prevention. The therapeutic Holy Grail in autoimmune disease is ‘negative’ vaccination against autoantigens that drive immune-mediated pathology, to induce disease-specific immune tolerance. This can be achieved by administering autoantigen via a ‘tolerogenic’ (e.g. mucosal) route, cell (e.g. resting dendritic cell), mode (e.g. with blockade of co-stimulation molecules) or form (as an ‘altered peptide ligand’). These strategies to induce immune tolerance are effective in rodent models of autoimmune disease, but in application to humans the results have so far been disappointing. This review discusses the prospects of vaccination to prevent T1D, focusing on autoantigen-specific mucosal tolerance.




RESEARCH PAPERS

Open Access Article

Development of an Approach for the Laboratory Toxicological Evaluation of Bordetella Pertussis Adenylate Cyclase Genetic Toxoid Constructs as Multipurpose Vaccine

Sandra Prior, Michael J. Corbel and Dorothy K.L. Xing
Pages 151 - 159
http://dx.doi.org/10.4161/hv.1.4.1972
Abstract | PDF

Detoxified recombinant CyaA constructs have been developed as potential viral and tumoral epitope carriers for immunoprophylactic and therapeutic vaccination and as antigen candidates for inclusion in acellular pertussis vaccines. In this work, we attempt to explore a test system for the laboratory safety evaluation of CyaA preparations. Endotoxin was determined in vitro by the Limulus amoebocyte lysate assay. Cytotoxicity was measured by a tetrazolium salt test and a lactate dehydrogenase release assay using murine and human phagocytic cell lines. Cell viability was < 50% at concentrations > 1 ?g/mL of the wild type toxin and concentrations in the nanogram range inhibited the zymosan-induced oxidative burst as measured by chemiluminescence. However, no effects were observed for detoxified and non-acylated forms of CyaA at comparable and higher toxin concentrations. Effects found in the in vitro assays could not be related to the in vivo mouse weight gain test used as a general toxicity test. In vitro cytotoxicity and oxidative burst studies on phagocytes, and the evaluation of endotoxin levels are useful for safety screening of CyaA constructs. However, in vivo specific toxicity tests and potential toxic implications of enzymatic activity-independent effects of CyaA on cell function should be investigated.

Open Access Article

The Natural History of Untreated HIV Infection in Lima, Peru: Implications for Clinical Trial Endpoints for CTL Based HIV Vaccines

Daniel Corey, Hyung Woo Kim, Raul Salazar, Luis M. Gutierrez, Jorge Sánchez and Stephen R. Tabet
Pages 160 - 164
http://dx.doi.org/10.4161/hv.1.4.1976
Abstract | PDF

Most candidate HIV vaccines are directed at priming memory T cell responses and are being evaluated on their effects on post acquisition viremia and/or disease progression. These vaccines are being studied in areas of high HIV-1 prevalence. As such, we evaluated the frequency of CD4+ T cell decline and time course of opportunistic infections of patients presenting at a major metropolitan hospital in Lima, Peru, an area where such candidate vaccines are being tested. We examined 92 patients with untreated HIV-1 in calendar year 2002: 35% presented with CD4+ T cell counts of <200, 25% between 201 and 400, and 17% with >400 cells/mm3, 30 of 92 patients presented with overt AIDS, 6 were without an AIDS defining OI but CD4 counts <200. Over the course of follow-up, CD4 count decreased by a mean of 31 cells/mm3/year in women and 28 in men (p>0.5). Among persons presenting with CD4 counts >250 cells/mm3, the median time to first OI was 3.5 years. If clinical endpoints are required to evaluate the clinical effectiveness of T cell based vaccines, extended clinical follow-up of subjects enrolled in such trials will be required.

Open Access Article

Investigation in a Model System of the Effects of Combinations of Anthrax and Pertussis Vaccines Administered to Service Personnel in the 1991Gulf War

Sjoerd G. Rijpkema, Trudy Adams, Peter Rigsby, Dorothy K. Xing and Michael J. Corbel
Pages 165 - 169
http://dx.doi.org/10.4161/hv.1.4.1989
Abstract | PDF

The toxicity and immunogenicity of the anthrax and pertussis vaccine combinations used in the 1991 Gulf War was assessed in NIH, A/J and Balb/c mice. Inoculation of pertussis vaccines, vaccine combinations, or aluminium salt caused illness, splenomegaly and significant weight loss. Although some animals recovered eventually, a lethal form of ascites developed in some NIH mice and body weights of A/J and Balb/c mice remained below normal levels. Inoculation of anthrax vaccine produced little effect. Exposure to diluted vaccine combinations produced less serious side effects of shorter duration. Single vaccinations induced specific IgG1 antibodies whereas a mixture of IgG1 and IgG2a was produced after multiple injections. Antigen stimulation of spleen cells from mice exposed to pertussis vaccines induced high levels of NO and IL-6, whereas stimulated spleen cells from mice exposed to anthrax vaccine produced only low levels of IL-6. In mice, pertussis vaccines act as an adjuvant for anthrax vaccine, but these vaccines are also the major cause of toxicity of the vaccine combination. The relatively high vaccine dose used, together with the low sensitivity of mice to anthrax toxin, emphasises that caution should be exercised in applying these results to human recipients of these vaccines.

Open Access Article

Potency of Cell-Mediated Immune Responses to Different Combined HIV-1 Immunogens in a Humanized Murine Model

Ali Azizi, Masoud Ghorbani, Marko Kryworuchko, Susan Aucoin and Francisco Diaz-Mitoma
Pages 170 - 176
http://dx.doi.org/10.4161/hv.1.4.1990
Abstract | PDF

In this study, cell-mediated immune responses were evaluated in HLA-A2.1 mice that received polycistronic vector expressing HIV-1 gp120, gag and pol or single vectors expressing gp120 +gag/pol as well as recombinant structural proteins and adjuvants. Mice primed with the polycistronic DNA/CpG and boosted with the same regimen plus proteins induced a higher T-cell proliferative response to gp120. However, a very high frequency of IFN-gamma was detected in mice received the mixture of gp120 + gag/pol DNA constructs, recombinant proteins and CpG. We also measured specific CD8+T cells by intracellular cytokine staining and dimer assay in response to HIV-1 peptides specific for HLA-A2.1 in PBMCs without in vitro expansion. The group that received single gp120+gag/pol DNA constructs, recombinant proteins and CpG had a higher CD8+T cell response to the mixture of peptides in comparison with the other groups that received the polycistronic construct. The present study reveals an optimal combination of immunogens to increase immune responses against HIV-1.