Table of Contents

Volume 3, Issue 5

  September/October 2007

  Pages 155 - 228

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 Issue Catalogue (MARC XML)

LETTERS

Open Access Article

Assessing the Safety of Post-Exposure Rabies Immunization in Pregnancy

Subhash C. Arya and Nirmala Agarwal
Page 155
http://dx.doi.org/10.4161/hv.3.5.4587
PDF

Open Access Article

ELISA Assays for Rabies Antibodies?

Gerlind Anders and Hoshang B. Vakil
Page 156
http://dx.doi.org/10.4161/hv.3.5.5060
PDF




RESEARCH PAPERS

Open Access Article

Vaxfectin™-Formulated Influenza DNA Vaccines Encoding NP and M2 Viral Proteins Protect Mice against Lethal Viral Challenge

Gretchen S. Jimenez, Rodrick Planchon, Qun Wei, Denis Rusalov, Andrew Geall, Joel Enas, Peggy Lalor, Vicky Leamy, Ruth Vahle, Catherine J. Luke, Alain Rolland, David C. Kaslow and Larry R. Smith
Pages 157 - 164
http://dx.doi.org/10.4161/hv.3.5.4175
Abstract | PDF

Next generation influenza vaccines containing conserved antigens may enhance immunity against seasonal or pandemic influenza virus strains. Using a plasmid DNA (pDNA)-based vaccine approach, we systematically tested combinations of NP, M1, and M2 antigens derived from consensus sequences for protection against lethal influenza challenge and compared formulations for adjuvanting low pDNA vaccine doses. The highest level of protection at the lowest pDNA doses was provided by Vaxfectin™-formulated NP + M2. Vaxfectin™ adjuvanticity was confirmed with a low dose of HA pDNA. These promising proof-of-concept data support the clinical development of Vaxfectin™-formulated pDNA encoding NP + M2 consensus proteins.

Open Access Article

Rabies Antibody Levels in Bat Handlers in the United Kingdom: Immune Response Before and After Purified Chick Embryo Cell Rabies Booster Vaccination

Jill Morris, Natasha S. Crowcroft, Anthony R. Fooks and Nick Andrews
Pages 165 - 170
http://dx.doi.org/10.4161/hv.3.5.4216
Abstract | PDF

Periodic rabies booster injections are recommended for persons who are at continued risk of rabies exposures, but literature on booster intervals is not comprehensive. We recruited bat workers who received rabies vaccinations between September 2002 and March 2003 either as a primary rabies vaccination course (primary group) or rabies booster vaccination (secondary group). From September 2004, those bat workers in the primary group had two blood tests to determine their rabies antibody level; one immediately prior to their first booster vaccination and one approximately one month after the booster vaccination. Bat workers in the secondary group had one blood test, approximately two years after their last booster vaccination. Overall, 185 bat workers participated in the study: 145 in the primary group, 40 in the secondary group. Sixteen (11.1%) in the primary group were below the minimum recognized rabies antibody level of 0.5 IU/ml prior to their first booster vaccination; all were above this level one-month after their booster. All bat workers in the secondary group had a rabies antibody level above 0.5 IU/ml. In the primary group, age of the bat worker at primary immunization and rabies vaccine type were significantly associated with antibody response to the rabies booster. We recommend that the first rabies booster vaccination is given one year after the primary course and subsequent boosters are given every three to five years thereafter.

Open Access Article

Trust and Experience as Predictors of HPV Vaccine Acceptance

Laura A.V. Marlow, Jo Waller and Jane Wardle
Pages 171 - 175
http://dx.doi.org/10.4161/hv.3.5.4310
Abstract | PDF

Background – Awareness of factors associated with uptake of new childhood vaccinations could help physicians to focus attention on those parents who are most likely to decline and ensure that they are fully informed before making a vaccination decision. Aim - To examine the association between general vaccine attitudes, trust in doctors and the government, past experience with vaccination, and acceptance of HPV vaccination. Design - School-based survey. Setting - Questionnaires were sent through 10 schools in England. Participants - Questionnaires were sent to 1205 mothers of 8-14 year old girls. Responses from 684 mothers were included in analyses. Outcome measures - Intended acceptance of prophylactic HPV vaccination. Results - Mothers who had high trust in doctors or the government were more likely to accept the vaccine (OR=1.35, CI: 1.22-1.50), as were those who believed their own doctor would take their vaccine concerns seriously (OR=1.70, CI: 1.23-2.36). Mothers who had delayed (OR=0.31, CI: 0.19-0.51), refused (OR=0.33, CI: 0.18-0.59), or regretted (OR=0.43, CI: 0.19-0.99) a previous paediatric vaccination were less likely to accept the HPV vaccine. The child having experienced adverse effects from a previous vaccination was not significantly associated with acceptance (OR=0.48, CI: 0.21-1.10). Conclusions - Past experience and trust in doctors and government were associated with differential acceptance of a new vaccine. These results suggest that doctors should listen to parents' worries about vaccination, especially parents who have previously delayed or refused vaccines. It may also be beneficial for health information to emphasize the general importance of vaccination as an effective disease prevention strategy.

Open Access Article

A Retrospective Study on the Quality of Haemophilus Influenzae Type B Vaccines Used in the U.K. Between 1996 and 2004

Barbara Bolgiano, Fatme Mawas, Karena Burkin, Dennis T. Crane, Manolya Saydam, Peter Rigsby and Michael J. Corbel
Pages 176 - 182
http://dx.doi.org/10.4161/hv.3.5.4352
Abstract | PDF

Following the reduction in efficacy of Hib-TT vaccines in the primary immunization schedule observed in the U.K. between 1999 and 2003, batches of vaccine manufactured by two different companies were retrospectively examined by the National Institute for Biological Standards and Control. The study evaluated 41 batches of the Hib-TT vaccines manufactured between 1994 and 2003, assaying potency (total PRP saccharide content), integrity (% free saccharide), consistency (molecular sizing), and immunogenicity, as well as reviewing data previously obtained at the time of release. The study indicated the stability of the lyophilized final fill vaccines to extend well past their assigned shelf-lives, and found no trends in the endotoxin content, total saccharide or % free saccharide content. A trend towards slightly larger conjugates was observed over time in Hib-TT A, evidenced in both the manufacturer’s data obtained at the time that samples were submitted for testing and in data obtained from the retrospective analysis. The study confirmed that that there had been no significant change in the quality of the Hib vaccines that could possibly account for the change reported in their protective efficacy in the U.K. The study also demonstrated the value of independent testing of vaccines from the time of licensure and in the ongoing monitoring and re-examination of selected batches, as necessary, to assure their continuing quality, safety and consistency.

Open Access Article

Immunogenicity of Two Modern Tissue Culture Rabies Vaccines in Pre-Exposure Prophylaxis

P.S. Kulkarni, Sidram K. Raut, Suresh S. Jadhav, Subhash V. Kapre and Nileema Deuskar
Pages 183 - 186
http://dx.doi.org/10.4161/hv.3.5.4360
Abstract | PDF

Pre-exposure prophylaxis was given to employees supposed to be involved in rabies vaccine production in India. Prior to availability of the manufacturer’s own human diploid cell (HDC) vaccine (Rabivax®), immunization was executed with a chick embryo cell (CEC) vaccine (Rabipur®). This constellation gave an opportunity to compare retrospectively immunogenicity of these two vaccines. The data was collected by retrospective analysis over more than 3 years at the clinic of Serum Institute of India Ltd. As per the standard protocol, persons with negative rabies vaccination history receive a dose of 1 ml of rabies vaccine intramuscularly on day 0, 7 and 28, and the virus anti-glycoprotein antibodies are measured one month after the third dose. The antibody levels ≥ 0.5 IU/ml are considered protective. The CEC and HDC vaccines were used during the analysis period. In all, 43 individuals received the CEC vaccine, 106 the HDC vaccine. The mean age of recipients was 33 years 5 months (Rabipur®) and 30 years 3 months (Rabivax®). All subjects in both groups were males. Five commercial batches of the CEC vaccine (129 doses) and seven batches of the HDC vaccine (318 doses) were used. 99% of the HDC and 93% of the CEC vaccine recipients were protected after the standard 3 dose schedule. Geometric mean titre was significantly greater for the HDC than CEC vaccine, being 5.05 IU/ml and 2.90 IU/ml, respectively (P=0.0002). The HDC vaccine showed a good lot-to-lot consistency with respect to GMT both by ANOVA test and Nonparametric ANOVA test. On the other hand, the CEC vaccine demonstrated a variation in titres, when the lots were compared. Three out of four low-responders accepted a booster vaccination, and regardless of whether Rabipur® or Rabivax® was used, all three responded well 1 month after the booster. The Indian HDC vaccine compares well with the CEC vaccine in terms of immunogenicity. With HDC vaccines, cost has been an issue. However, since the new HDC vaccine has a comparable cost to the CEC vaccine, it may be possible to use it in large-scale vaccinations.

Open Access Article

Anticapsular Polysaccharide IgG Concentrations in Mexican Children Formerly Immunized with Haemophilus Influenzae b Prp-T Vaccine

Patricia Gómez de León, F. Javier Díaz García, Jose Luis Arredondo, Jorge Jorge, Silvia Giono Cerezo and Jose I. Santos
Pages 187 - 191
http://dx.doi.org/10.4161/hv.3.5.4376
Abstract | PDF

Background: In 1999 H. influenzae b (Hib) PRP-T vaccine was introduced into primary immunization schedule in Mexico. There have been no studies evaluating antibody response after widespread immunization in our country. It is now recognized that Hib conjugates induce significant initial antibody levels that in some cases wane over time. This study relies on the measurement of IgG serum antibody concentrations to Hib capsular polysaccharide (PS) and is interpreted in the light of the accepted levels ≥ 0.15 µg/mL for short-term protection against Hib invasive disease and ≥ 5.0 µg/mL for protection against Hib oropharyngeal carriage. Methods: Using a validated ELISA assay, we measured the IgG serum antibody concentrations in 115 children between 7 and 93 months of age who had received three doses of PRP-T. We used the standard reference serum US FDA 1983 for quantification of PS antibody levels. Concentrations were estimated using 3rd degree polynomial regression lines. As there was no unvaccinated group available (>95% of Mexican children have received the Hib vaccine), the study was designed as a cross-sectional. Results: All children had serum IgG concentrations ≥ 0.15 µg/mL [range 0.24-54.64 µg/mL]; 69.6 % (80/115) had ≥1.0 µg/mL and 14% (16/115) showed concentrations ≥5.0 µg/mL. The vaccine elicited geometric mean concentrations (GMC) of 4.0, 1.6, 1.4 and 2.4 µg/mL in groups of 7-12, 13-24, 25-48 and 49-93 month-old respectively. Conclusions: PRP-T vaccination in this group of Mexican children has resulted in serum IgG concentrations ≥ 0.15 µg/mL, suggesting that Hib immunization has conferred protection against invasive disease.

Open Access Article

Use of Neutralizing Murine Monoclonal Antibodies to Rabies Glycoprotein in Passive Immunotherapy Against Rabies

Kader Muhamuda, Shampur N. Madhusudana and Vasanthapuram Ravi
Pages 192 - 195
http://dx.doi.org/10.4161/hv.3.5.4386
Abstract | PDF

Passive immunization is an important parameter of post exposure rabies prophylaxis. Two types of rabies immunoglobulin (RIG) are currently available for Passive immunization against rabies i.e human rabies immunoglobulin (HRIG) and equine rabies immunoglobulin (ERIG). The former is very expensive and not easily available and the latter causes side effects because of which its utility is limited. In the present study we have produced murine monoclonal antibodies (Mabs) to rabies glycoprotein (G) and studied their utility in passive immunization against rabies using animal models. Their efficacy was compared to commercially available ERIG both in terms of neutralizing titer and effective protein concentration. The neutralizing titers of these Mabs ranged from 1650 IU/mL to 75,000 IU/mL by RFFIT. They belonged to the IgG 2 a subclass. The Mabs were able to protect 70 to 100% of mice and guinea pigs inoculated with rabies viruses, depending on the strain of the virus. These Mabs were found to be 2000 time more potent than commercial ERIG in terms of effective protein concentration and neutralizing titer. Further studies are required to study their utility in humans exposed to rabies.

Open Access Article

Post-Marketing Safety Monitoring of a New Group B Meningococcal Vaccine in New Zealand, 2004-2006

Anne McNicholas, Yvonne Galloway, Paul Stehr-Green, Stewart Reid, Sarah Radke, Kerry Sexton, Charlotte Kieft, Claire Macdonald, Jocelyn Neutze, Ross Drake, Dorothy Isaac, Mary O'Donnell, Michael Tatley, Philipp Oster and Jane O’Hallahan
Pages 196 - 204
http://dx.doi.org/10.4161/hv.3.5.4458
Abstract | PDF

New Zealand introduced a new outer membrane vesicle vaccine in 2004 to combat an epidemic of group B meningococcal disease. An Independent Safety Monitoring Board oversaw intensive safety monitoring, which included hospital surveillance, health professional reporting (passive and active) and mortality monitoring. With over three million doses administered to individuals aged under 20 years, the monitoring results provide consistent evidence supporting the vaccine’s safety.

Open Access Article

Safety, Reactogenicity, and Immunogenicity of a Recombinant Protective Antigen Anthrax Vaccine Given to Healthy Adults

James D. Campbell, Kristin H. (Long) Clement, Steven A. Wasserman, Sarah Donegan, Lisa Chrisley and Karen L. Kotloff
Pages 205 - 211
http://dx.doi.org/10.4161/hv.3.5.4459
Abstract | PDF

BACKGROUND: Bacillus anthracis causes anthrax, a vaccine-preventable zoonotic disease that may follow intentional or unintentional exposure to its spores. Although an anthrax vaccine is currently licensed in the USA, better vaccines are desirable for both pre- and post-exposure prophylaxis.

METHODS: Healthy adults, aged 18 to 40 years, received anthrax immunization with either licensed Anthrax Vaccine Adsorbed (AVA, BioThrax™), or an experimental recombinant Protective Antigen vaccine (rPA) produced from an avirulent, non-spore-forming strain of B. anthracis at one of 4 doses (5, 25, 50, or 75 μg). Volunteers were followed for safety, reactogenicity, and immunogenicity.

RESULTS: rPA vaccine was well tolerated with a low rate of local or systemic reactions. Although antibody responses were poor following unadjuvanted rPA administration, 89 and 100% of volunteers who received Alhydrogel-adjuvanted rPA given intramuscularly had 4-fold increases by enzyme-linked immunosorbent and toxin neutralization assays, respectively. Peak antibody responses to adjuvanted rPA given intramuscularly were equivalent to AVA, given either intramuscularly or subcutaneously, when measured by either assay.

CONCLUSION: This recombinant Protective Antigen anthrax vaccine, when given with the adjuvant Alhydrogel to healthy adults in 2 intramuscular injections 4 weeks apart, is very well-tolerated and highly immunogenic.

Open Access Article

Knowledge of Spanish Parents About Their Children’s Vaccinations During the Decade 1993-2003

Pilar Carrasco-Garrido, Angel Gil de Miguel, Valentin Hernandez Barrera and Rodrigo Jimenez-Garcia
Pages 212 - 216
http://dx.doi.org/10.4161/hv.3.5.4500
Abstract | PDF

This study aims to analyse the knowledge of Spanish parents about the officially recommended vaccinations for their children. We analysed 3653 questionnaires from the Spanish National Health Surveys for the years 1993 and 2003. We used as a dichotomous dependent variable (“yes” or “no”) the question “For which of the following diseases do you think vaccination is officially recommended?” As independent variables, we used sociodemographic data and perceived health of the child. Knowledge of five of the seven recommended vaccinations decreased during the decade of the study. Logistic regression associates highly educated Spanish parents with decreased knowledge of vaccines. When analysing the global outcome of vaccines recommended during the decade, we can see that, in 2003, parents had less knowledge about vaccines (OR: 0.54, CI 95%: 0.40-0.73) than in 1993.




COMMENTARIES

Open Access Article

Vaccination and Risk Groups: How Can We Really Protect the Weakest?

Paolo Bonanni
Pages 217 - 219
http://dx.doi.org/10.4161/hv.3.5.4351
Abstract | PDF

Subjects who for their clinical conditions, age, occupational activities or living situations, are at increased risk of acquiring preventable infectious diseases or suffering from their complications, are the object of periodical attempts of identification and offer of vaccination. Several examples can be drawn from the past and from more recent experiences showing that targeted vaccination strategies usually fail to reach most of these subjects. As a matter of fact, obtaining a very high vaccination coverage in risk groups implies a complex integration of responsibilities in identifying, contacting, communicating with and immunizing many different categories of subjects. On the contrary, routine vaccination strategies of one or more cohorts of subjects have always shown the ability (if well implemented) to protect the weakest individuals in the community, due to the establishment of such a community protection as to get a remarkable positive impact even on those that are not immunized. It is ethically unsustainable that universal immunization strategies for diseases with remarkable impact and severity are delayed until an adequate coverage has been reached in subjects at risk, because this would paradoxically mean a serious damage just for those people that are the theoretical object of protection efforts through targeted vaccination strategies.

Open Access Article

Optimisation of Oral Immunization Through Receptor-Mediated Targeting of M Cells

A. Ruth Foxwell, Allan W. Cripps and Jennelle M. Kyd
Pages 220 - 223
http://dx.doi.org/10.4161/hv.3.5.4358
Abstract | PDF

Only a small number of oral vaccines are available for routine immunisations despite a significant research effort and a number of obvious advantages over parenteral vaccination. The major roadblock in the development of oral vaccines has been mostly attributed to a lack of ability to specifically target antigen to the mucosal immune system of the gastrointestinal tract. This commentary examines the accessing of M cells through receptor interaction on the apical surface of the cell in order to enhance the efficiency and efficacy of oral immunisation. Three challenges have been identified (i) the availability of appropriate experimental models to study M cell targeting and transcytosis; (ii) appropriate tools for investigating the specificity of targeting; and (iii) the identification of priority targets on the apical surface of M cells.

Open Access Article

Immune Surveillance as a Rationale for Immunotherapy?

Anastas Pashov, Behjatolah Monzavi-Karbassi, Marie Chow, Martin Cannon and Thomas Kieber-Emmons
Pages 224 - 228
http://dx.doi.org/10.4161/hv.3.5.4407
Abstract | PDF

The identification and replication of successful processes or best practices is a standard management operating model adopted in diverse environments, e. g. – business, medical practice and even in scientific research. Here, we present a thought experiment on its applicability to developing cancer immunotherapeutics. This thought experiment provides a framework for reassessing the pros and cons of existing approaches and new ideas. It turns out that replication of a best practice can be surprisingly difficult. Tinkering with an operation that is efficient or trying to combine practices to create the perfect hybrid might lend to problems.