Table of Contents

Volume 5, Issue 8

  August 2009

  Pages 507 - 571

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 Issue Catalogue (MARC XML)

EDITOR'S CORNER

Open Access Article

Letter from the Editor

Ronald W. Ellis and Eva Riedmann
Page 507
http://dx.doi.org/10.4161/hv.5.8.9670
PDF




MEETING REPORT

Open Access Article

The 3rd international conference on Influenza Vaccines for the World- IVW 2009

Tamar Ben Yedidia
Pages 508 - 509
http://dx.doi.org/10.4161/hv.5.8.9108
Abstract | PDF

The Influenza Vaccines for the World (IVW 2009) conference was held in Cannes, France, 27-30 April 2009. Scientists and Influenza experts from academia and industry joined to discuss influenza vaccines and related issues, to report the latest data and trends associated with current and new influenza vaccines and their worldwide availability and delivery. Specific interest was in influenza vaccine effectiveness and surveillance, stockpiling and preparedness for pandemic outbreaks as well as adjuvants and the development of novel vaccines for seasonal and pandemic influenza vaccines.




REVIEWS

Open Access Article

Manipulation of T_H17 responses in pulmonary immunity and disease through vaccination

Gregory F. Sonnenberg and David B. Weiner
Pages 510 - 519
http://dx.doi.org/10.4161/hv.5.8.8879
Abstract | PDF

Since the discovery of a novel subset of CD4+ T helper cells, T_H17 cells have been implicated in a wide range of human diseases, including autoimmunity, allergic reactions, and auto-inflammatory diseases.  Conversely, it has also been determined that T_H17 cells are required to mount a protective immune response to a number of pathogens.   It has therefore been of great interest to manipulate T_H17 responses to either prevent disease or promote immunity.  Vaccination is a particularly attractive approach for this manipulation.  With a focus on the pulmonary mucosal environment, we herein review T_H17 responses and potential methods for manipulation.

Open Access Article

Advances in dengue vaccine development

Kanakatte Raviprakash, Gabriel Defang, Timothy Burgess and Kevin Porter
Pages 520 - 528
http://dx.doi.org/10.4161/hv.5.8.9008
Abstract | PDF

Dengue viruses are the most important arboviruses causing human disease. Expansion of the disease in recent decades to include more geographical areas of the world, an appreciation of the disease burden and market potentials have spurred a flurry of activity in the development of vaccines to combat dengue viruses. Recent progress in this area and some of the obstacles associated with this development are discussed.




RESEARCH PAPERS

Open Access Article

A heat-stable hepatitis B vaccine formulation

Jan Jezek, Dexiang Chen, Lynne Watson, Jill Crawford, Shalimar Perkins, Anil Tyagi and LaToya Jones Braun
Pages 529 - 535
http://dx.doi.org/10.4161/hv.5.8.8600
Abstract | PDF

The purpose of the present study was to develop a formulation of recombinant hepatitis B vaccine with improved stability at elevated temperatures. A validated, in vitro, antigen reactivity assay was used to measure the stability of the vaccine. The formulation development focused on modification of the interactions between the antigen and aluminum hydroxide adjuvant and subsequent optimization of the ionic aqueous environment of the adsorbed vaccine. A formulation of hepatitis B vaccine containing 40 mM histidine and 40 mM phosphate at pH 5.2 had considerably improved stability at elevated temperatures as measured by the in vitro antigen reactivity assay. The formulation exhibited 9-week stability at 55°C and was subsequently shown to be stable both at 37°C and at 45°C for at least 6 months based on the in vitro antigen reactivity and immunogenicity in mice. The formulation comprises only excipients which have a history of safe use in approved drug products. The new vaccine formulation has the potential to be used outside the cold chain for part of its shelf life. This may improve the immunization coverage, simplify the logistics for outreach immunization, and ensure the potency of the vaccine in areas where the cold chain is insufficient.

Open Access Article

Evaluation of a plasmid DNA-based anthrax vaccine in rabbits, nonhuman primates and healthy adults

Wendy A. Keitel, John J. Treanor, Hana M. El Sahly, Thomas G. Evans, Scott Kopper, Vanessa Whitlow, Cheryl Selinsky, David C. Kaslow, Alain Rolland, Larry R. Smith and Peggy A. Lalor
Pages 536 - 544
http://dx.doi.org/10.4161/hv.5.8.8725
Abstract | PDF

VCL-AB01, a cationic lipid-formulated plasmid DNA (pDNA)-based vaccine that contains genes encoding genetically detoxified B. anthracis protective antigen (PA) and lethal factor (LF), was assessed in a Phase 1, dose-escalating clinical trial in healthy adults for safety and immunogenicity, and in nonhuman primates  for immunogenicity and efficacy against challenge with a lethal dose of B. anthracis spores.  Healthy 18-45 year old subjects were randomly assigned to receive either the investigational vaccine containing 0.2 mg, 0.6 mg, or 2 mg of total pDNA per dose, or saline placebo, administered at 0, 1, and 2 months.  The 0.2 mg and 0.6 mg dose levels were generally well tolerated; however, dose-limiting reactogenicity was observed among subjects given the first 2 mg dose and the remaining 2 injections in the 2 mg group were reduced to 0.6 mg.  Dose-related increases in seroconversion frequencies were observed. Overall, 10%, 33.3% and 80% of subjects in the 0.2, 0.6 and 2 mg groups, respectively, developed antibodies to PA and/or LF as measured by ELISA; however, antibodies with toxin neutralizing activity (TNA) were detected in only 1 subject.  In monkeys that received a 0.6 mg dose 3 times at 2 week intervals, low levels of antibodies were detected by ELISA but not by the TNA assay in all animals just prior to challenge.  Despite the absence of TNA, 3/4 animals survived the lethal challenge.  In summary, VCL-AB01 was generally well tolerated in humans at a dose that provided immunity in monkeys despite the lack of robust TNA titers in either species.

Open Access Article

Worksite policies related to influenza vaccination: A cross-sectional survey of US registered nurses

Sarah J. Clark, Anne E. Cowan and Pascale M. Wortley
Pages 545 - 550
http://dx.doi.org/10.4161/hv.5.8.8806
Abstract | PDF

To increase the rate of influenza vaccination among healthcare personnel, national recommendations call for worksites to adopt a multi-pronged strategy to encourage vaccination.  The objective of this study was to explore existing worksite influenza vaccination policies and attitudes toward the use of declination forms based on a cross-sectional mail survey of 2,000 registered nurses in four US states.  The majority (59%) of respondents reported receiving influenza vaccine during the 2005-06 influenza season.  Just over half (55%) of respondents reported that their worksite strongly recommended influenza vaccination for employees.  Most worksites made vaccine available to employees via one or more venues (95%) and used one or more strategies to inform employees about influenza vaccination (91%).  Worksite policies supportive of HCP influenza vaccination were reported more frequently by vaccinated nurses and those in hospital-based settings.  The majority of respondents supported the use of declination forms for influenza vaccination.  Although many healthcare worksites have policies in place to support influenza vaccination among their employees, continued efforts to expand worksite policies and practices are important for increasing vaccination rates and may need to be targeted differently for hospital- and non-hospital-based settings.

Open Access Article

Seropersistence of tick-borne encephalitis antibodies, safety and booster response to FSME-IMMUN^® 0.5 ml in adults aged 18-67 years

Alexandra Loew-Baselli, Eva-Maria Poellabauer, Borislava G. Pavlova, Sandor Fritsch, Manuela Koska, Roman Bobrovsky, Ryszard Konior and Hartmut J. Ehrlich
Pages 551 - 556
http://dx.doi.org/10.4161/hv.5.8.8571
Abstract | PDF

A clinical study was carried out to evaluate the persistence of tick-borne encephalitis (TBE) antibodies 2 and 3 years after a primary vaccination series (three-dose regimen), and to assess the antibody response to a booster vaccination with FSME-IMMUN®. Volunteers (N=347, 18–67 years) who had received 2 doses of either FSME-IMMUN® or Encepur® adults and a third vaccination with FSME-IMMUN® were enrolled. Seropositivity rates were assessed by ELISA and neutralization test (NT). After the primary series, seropositivity rates were 99.1% as determined by ELISA and 100% by NT, decreasing to 85% and 96.8% in the first 2 years and to 88.7% and 95.4% after 3 years. Following booster vaccination, 100% of subjects were seropositive. Age was the only variable with a significant influence on the probability of remaining TBE seropositive 2 or 3 years after the third vaccination. In subjects aged 18–50 years, the pre-booster seropositivity rate was higher (88.7% and 92.3% after 2 and 3 years, respectively) than in those aged 51–67 years (65.5% and 70.9% after 2 and 3 years, respectively). Adverse events after booster vaccination occurred with a low frequency and were predominantly mild. An annual TBE antibody decline rate of 0.58 (based on NT) was estimated to lead to antibody titer decrease from e.g. 260 to 45.6 after 3 years. To conclude, a booster vaccination with FSME-IMMUN®, administered 3 years after primary vaccination, is well tolerated and induces a substantial immune response regardless of vaccine used in the primary series.

Open Access Article

Disparities in preschool immunization coverage associated with maternal age

Daniel A. Salmon, Philip J. Smith, William K.Y. Pan, Ann Marie Navar, Saad B. Omer and Neal A. Halsey
Pages 557 - 561
http://dx.doi.org/10.4161/hv.5.8.9009
Abstract | PDF

Associations between maternal age and preschool immunization coverage are unclear.  This study aimed to determine if maternal age is associated with preschool immunization coverage and the importance of maternal age compared with other factors affecting vaccination coverage.  Data from the 2001-2003 National Immunization Survey (NIS) were used to estimate vaccine coverage.  Children were considered up-to-date (UTD) if they received ≥4 doses of DTaP, ≥3 doses of polio, ≥1 doses of MMR, ≥3 doses of Hib, and ≥3 doses of Hep B.  Bivariate and multivariate relationships between UTD coverage and maternal, child and household factors were evaluated.  Classification tree analysis assessed complex interactions between maternal, child, and household factors associated with UTD coverage and isolated the most important factors in predicting UTD coverage.  UTD coverage was significantly associated with maternal age: coverage increased as maternal age increased.  Coverage among children with 17-year-old mothers was 64%; coverage among children of mothers 17 - 26 years old increased by 16.3% overall (approximately 1.8% per year). After 26 years of age, coverage did not increase significantly as maternal age increased. The relationship between maternal age and UTD coverage remained statistically significant after adjusting for a broad range of maternal, child and household factors.  Classification tree analysis suggested that maternal age is the most important factor associated vaccine coverage.  More research is needed to determine the reasons for underimmunization of children born to young mothers.




COMMENTARIES

Open Access Article

Understanding protective immune mechanisms induced by malaria vaccines in the context of clinical trials

Carlota Dobaño and Joseph J. Campo
Pages 562 - 565
http://dx.doi.org/10.4161/hv.5.8.8313
Abstract | PDF

Malaria is one of the world’s most important diseases, and an effective, licensed vaccine would be a major public health tool. There is currently a surge in efforts to develop malaria vaccines, and many candidates are entering and progressing through clinical trials. However, inadequate understanding of host immunity, gaps in knowledge of parasite biology and the lack of surrogate markers of protection have hindered rational vaccine development and led to failure to control malaria. A greater understanding of naturally acquired immunity would certainly help guide vaccine development and deployment.
The research tools at our disposal are greater and superior than before, and the growing capacity to perform immunological assays in the field brings new possibilities for investigating vaccine-induced immunity and immune correlates of protection within clinical trials. The malaria vaccine community needs to learn from the TB and HIV vaccine communities, who have developed and optimized multi-parameter immunological assays, some of which are amenable for studies conducted in African children. The best strategy is to take advantage of large clinical trials in endemic countries to better understand immunity to malaria, vaccine take and identify surrogates of protection.


Open Access Article

Dengue vaccines: A new hope?

Viroj Wiwanitkit
Pages 566 - 567
http://dx.doi.org/10.4161/hv.5.8.8481
Abstract | PDF

Dengue infection is an important arboviral infection that has become a public health concern. Dengue vaccination is the expected primary prevention for this infection. However, dengue vaccine is not presently available. In this article, the author discusses and comments on “problem”, “hope” as well as “present status” in dengue vaccine development.

Open Access Article

Advances in DNA immunization against hepatitis C virus infection: Opportunities and challenges

Liz Alvarez-Lajonchere and Santiago Dueñas-Carrera
Pages 568 - 571
http://dx.doi.org/10.4161/hv.5.8.8572
Abstract | PDF

Hepatitis C virus (HCV) causes chronic infection in approximately two thirds of cases, leading to chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma in a substantial proportion of the 170 million HCV-infected individuals worldwide. As there is neither prophylactic nor therapeutic vaccine for this virus, the research in this area is of special importance. Several vaccine candidates have been evaluated in pre-clinic, but just a few has reached the clinical evaluation. DNA immunization is one of the most evaluated approaches to obtain an effective vaccine against HCV infection. In the last few years a group of technical refinements in DNA vaccines has allowed to increase their immunogenicity. Two DNA vaccine candidates against HCV have already reached clinical evaluation, being well tolerated and immunogenic in HCV-chronically infected individuals. The main results, opportunities and challenges of DNA immunization against HCV are discussed further in the present commentary. DNA vaccination is already a valuable tool for research HCV. Further improvements in formulation and delivery devices might be sufficient for becoming a real alternative in HCV vaccine.