Table of Contents

Volume 4, Issue 3

  May/June 2008

  Pages 173 - 252

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 Issue Catalogue (MARC XML)

PORTRAIT OF A LEADING VACCINOLOGIST

Open Access Article

Chance and necessity

Nathalie Garçon
Pages 173 - 175
http://dx.doi.org/10.4161/hv.4.3.6226
PDF




REVIEWS

Open Access Article

Development of a Chlamydia trachomatis bacterial ghost vaccine to fight human blindness

Francis O. Eko, Talin Barisani-Asenbauer and extra-please delete
Pages 176 - 183
http://dx.doi.org/10.4161/hv.4.3.5393
Abstract | PDF

Trachoma is the world’s leading cause of preventable disease and the third most common cause of blindness after cataract and glaucoma, affecting an estimated 84 million people and leaving 590 million at risk. As a crippling disease, Trachoma causes an enormous loss of productivity and constitutes a major socioeconomic burden. Although antibiotics are effective in treating active cases of the illness, they do not prevent re-infection, which occurs with high frequency in susceptible populations. Also, once infection and pathology are established, treatment may be less effective. Another major public health challenge posed by trachoma is that a large number of infected individuals are asymptomatic and readily infect those with whom they interact. Thus, an inexpensive and easy to deliver vaccine for trachoma would be highly effective in reducing the devastation caused by this disease. Development of an effective vaccine for controlling and preventing trachoma will require an understanding of the complex immunological mechanisms that occur during infection, identifying those antigens that elicit a protective immune response and designing effective vaccine delivery systems. Significant progress has been made in the delineation of the immune correlates of protection that will form the basis of vaccine evaluation. Recent advances in chlamydial genomics and proteomics has identified a number of protective antigens or epitopes that when appropriately delivered will produce an efficacious vaccine. The challenge at this time is the development of effective methods for vaccine delivery. We have developed an effective bacterial ghost (BG) delivery system possessing intrinsic adjuvant properties and capable of simultaneously delivering multiple antigens to the immune system. Such a flexible delivery system can produce an effective vaccine that will prevent the development of trachomatous conjunctivitis and blindness. The safety and relatively cheap production cost of BG-based vaccines offer a technological and manufacturing advantage for a vaccine needed on a global scale.

Open Access Article

Genome‑based vaccine development: A short cut for the future

Danilo Gomes Moriel, Maria Scarselli, Laura Serino, Marirosa Mora, Rino Rappuoli and Vega Masignani
Pages 184 - 188
http://dx.doi.org/10.4161/hv.4.3.6313
Abstract | PDF

Bacterial infectious diseases remain a major cause of deaths and disabilities in the world. Although conventional vaccinology approaches were successful in conferring protection against several diseases, they failed in providing efficient vaccines against many others. Together to the sequencing of the first genome, a new chapter in the vaccinology history started to be written. Reverse vaccinology changed the way to think about vaccine development, using the information provided by the microorganisms’ genome against themselves. Since then, reverse vaccinology has evolved and helped researchers to overcome the limits of the conventional vaccinology approaches and led to the discovery and development of novel vaccines concerning emerging diseases, like Neisseria meningitidis B and Streptococcus agalactiae. A lot of work must be done, but deciphering the information provided by genome sequences and using it to better understand the host‑pathogen interactions has proved to be the key for protection.

Open Access Article

Genetic immunization: Bacteria as DNA vaccine delivery vehicles

Pablo Daniel Becker, Miriam Noerder and Carlos Alberto Guzmán
Pages 189 - 202
http://dx.doi.org/10.4161/hv.4.3.6314
Abstract | PDF

The so‑called DNA vaccination represents one of the most notable tools under development in the field of vaccinology. The concept of administering the gene coding for any given protective antigen and make responsible vaccinee’s own cells to produce the protein appeals as too simple to be true. Indeed, the implementation of this approach for mass vaccination should overcome several bottlenecks, such as need of high dosages and poor immunogenicity. In this context, the use of live attenuated bacteria as delivery system for plasmid DNA has emerged as a promising alternative to overcome many of those pitfalls. In addition, this approach is not only amenable for mucosal administration, but allows to specifically target professional antigen presenting cells. This results in their transfection, as well as in their activation and maturation, due to their built‑in adjuvant properties resulting from the stimulation of pattern recognition receptors. This chapter discusses the specific features that should be taken into consideration when designing a plasmid vector, current candidate bacterial carriers for DNA delivery and main safety issues.




RESEARCH PAPERS

Open Access Article

Immunogenicity and reactogenicity of acellular pertussis booster vaccines in children: Standard pediatric versus a reduced-antigen content formulation

Claudius U. Meyer, Pirmin Habermehl, Markus Knuf, Bernhard Hoet, Joanne Wolter and Fred Zepp
Pages 203 - 209
http://dx.doi.org/10.4161/hv.4.3.5290
Abstract | PDF

Booster vaccination with a reduced-antigen-content dTpa, pediatric DTPa or adult Td vaccine in DTPa-primed children aged 4-6 years was evaluated. Immunogenicity and CMI was assessed one month and 3.5 years after vaccination. Symptoms were solicited for 15 days post-vaccination. There were no differences between groups in diphtheria or tetanus seroprotection or pertussis vaccine-response rates. Anti-diphtheria and anti-PRN concentrations were higher after DTPa, but groups differences reduced over time. Non-significant trends toward reduced reactogenicity of dTpa were observed. Many factors influence vaccine choice at pre-school age. The dTpa vaccine was as immunogenic and possibly better tolerated than DTPa at this age.

Open Access Article

Formulation and characterization of a ten-peptide single-vial vaccine EP-2101, designed to induce cytotoxic T-lymphocyte responses for cancer immunotherapy

Melanie Beebe, Mingsheng Qin, Michael Moi, Sharon Wu, Hashem Heiati, Les Walker, Mark Newman, John Fikes and Glenn Y. Ishioka
Pages 210 - 218
http://dx.doi.org/10.4161/hv.4.3.5291
Abstract | PDF

Effective vaccines that mediate clinical responses in cancer patients may require generation of broadly specific cytotoxic T lymphocytes (CTL) directed against multiple epitopes and tumor-associated antigens (TAA). Pursuant to this goal we developed a synthetic peptide vaccine, EP-2101, composed of 10 synthetic peptide epitopes and formulated in Montanide® ISA 51 adjuvant. Nine of the HLA-A*0201-restricted CTL epitopes were derived from five well-characterized TAA. The universal HLA-DR binding epitope PADRE® was also included for T-cell help. Herein we describe studies on the formulation and characterization of the EP-2101 vaccine which supports generation of a sterile single-vial emulsion using standardized processes. The physicochemical properties of the peptides were highly disparate and as such, solubilization studies were required to identify a process which supported sterile filtration of the EP-2101 peptide mix. A homogenization-based formulation process with Montanide ISA 51 and 0.5 mg/ml of each peptide was developed to generate a water-in-oil emulsion. Physical studies indicated the vaccine emulsion to be stable, with little change in visual appearance, viscosity and water droplet size for at least 3 months. The physical stability of individual peptides in the vaccine emulsion was demonstrated using HPLC and immunogenicity of the vaccine formulation was confirmed in HLA-A*0201/Kb transgenic mice where T-cell responses could be induced to all epitopes in EP-2101 following vaccination. Our study process is scalable for production of approximately 1.5 liters of potent experimental vaccine for preclinical animal toxicity and phase 1 clinical testing in patients with breast, colon or lung cancer.

Open Access Article

Identification of genome-derived vaccine candidates conserved between human and mouse-adapted strains of H. pylori

Leonard Moise, Julie A. McMurry, Jacques Pappo, Dong-Soo Lee, Steven F. Moss, William D. Martin and Anne S. De Groot
Pages 219 - 223
http://dx.doi.org/10.4161/hv.4.3.5394
Abstract | PDF

Computational methods accelerate vaccine development by rapid identification of potential vaccine candidates. We screened the Helicobacter pylori J99 and 26695 genomes for T-cell epitopes using the epitope mapping algorithm EpiMatrix and selected 150 sequences for experimental validation in a pre-clinical mouse model. Because strains of H. pylori that infect humans do not generally infect mice, and the sequence of the mouse-adapted “Sydney” strain (SS1) is not publicly available, we used targeted PCR to confirm that epitopes we computationally predicted from the human H. pylori isolates J99 and 26695 are conserved in SS1. Epitopes conserved in SS1 were further analyzed for binding to MHC in vitro and for antigenicity in infected mice to select candidates for an epitope-based vaccine.

Open Access Article

Smallpox vaccination is not associated with infertility in a healthy young adult population

Isabel G. Jacobson, Gia Gumbs, Carter Sevick, Tyler C. Smith and Margaret A.K. Ryan
Pages 224 - 228
http://dx.doi.org/10.4161/hv.4.3.5436
Abstract | PDF

Concerns exist regarding reproductive health, including potential infertility, among young adults with military-related occupational exposures. This study evaluated infertility diagnoses in a large population of healthy young adults in relation to prior smallpox vaccination. Using a retrospective cohort design, the population consisted of United States military members eligible for smallpox vaccination in 2003-2004 who had electronic health care utilization records available through at least December 2005. Multivariable logistic regression models were applied to evaluate infertility among male and female populations separately. Among 253,973 men and 44,332 women included in these analyses, the adjusted odds of infertility diagnoses in those with prior smallpox vaccination were 0.94 (95% confidence interval [CI], 0.83-1.06) and 1.10 (95% CI, 0.94-1.28), respectively. Therefore, no association was found between smallpox vaccination and subsequent infertility diagnoses in either men or women. This study represents the first large epidemiologic investigation of infertility after the smallpox vaccine.

Open Access Article

Influenza vaccine for high-risk non-elderly adults: A national survey of subspecialists

Matthew M. Davis, Pascale M. Wortley, Serigne M. Ndiaye, Anne E. Cowan, Amanda D. Osta and Sarah J. Clark
Pages 229 - 233
http://dx.doi.org/10.4161/hv.4.3.5516
Abstract | PDF

Despite long-standing recommendations for non-elderly adults with certain chronic pulmonary, cardiovascular, and metabolic conditions to receive influenza vaccine, vaccination rates remain low. Visits to subspecialists represent an important vaccination opportunity, but little is known regarding subspecialists’ perceptions related to influenza vaccination. In February 2003, we conducted a cross-sectional mail survey of a random sample (N = 2,007) of board-certified cardiologists, endocrinologists, and pulmonologists from the entire United States who provided outpatient care to adults aged 18-64 years, to assess their patterns of and attitudes toward administering influenza vaccine to high-risk, non-elderly patients. The overall response rate was 33%. Among 621 eligible respondents, 483 stocked influenza vaccine in their practice (Stockers) and 138 did not stock the vaccine (Non-Stockers). Pulmonologists were most likely to stock vaccine and strongly recommend vaccination; cardiologists were least likely. Among Stockers, barriers to vaccination varied by subspecialty. Among Non-Stockers, the most common factor in the decision to not stock vaccine was the perception that patients will receive the vaccine elsewhere. Most subspecialists who provide care to a large proportion of high-risk, non-elderly persons recommend influenza vaccination to some degree, particularly pulmonologists. To reduce missed opportunities overall, subspecialists should be encouraged to vaccinate patients who say that they plan to get the vaccine elsewhere. For cardiologists in particular, barriers to stocking influenza vaccine and recommending vaccination more strongly must be addressed.

Open Access Article

Changes in DT vaccine frequency and indications for use following introduction of DTaP vaccine

Patti J. Benson, Lisa A. Jackson, Thomas G. Rees and John B. Dunn
Pages 234 - 237
http://dx.doi.org/10.4161/hv.4.3.5517
Abstract | PDF

Our population-based study among HMO members under seven years of age in 1993-2000 showed that frequency of diphtheria and tetanus toxoid vaccine (DT) use declined significantly following the introduction of acellular pertussis-containing (DTaP) vaccine. We also observed changes in indications for DT following the transition to DTaP among children under two years of age; notably, a decline in the proportion of children receiving DT due to a reported prior vaccine reaction and an increase in the proportion of children receiving DT due to parental request and a history of pertussis.

Open Access Article

The potential cost-effectiveness of vaccination against herpes zoster and post-herpetic neuralgia

Marc Brisson, James M. Pellissier, Stéphanie Camden, Caroline Quach and Philippe De Wals
Pages 238 - 245
http://dx.doi.org/10.4161/hv.4.3.5686
Abstract | PDF

A clinical trial has shown that a live-attenuated varicella-zoster virus vaccine is effective against herpes zoster (HZ) and post-herpetic neuralgia (PHN). The aim of this study was to examine the cost-effectiveness of vaccination against HZ and PHN in Canada. A cohort model was developed to estimate the burden of HZ and the cost-effectiveness of HZ vaccination, using Canadian population-based data. Different ages at vaccination were examined and probabilistic sensitivity analysis was performed. The economic evaluation was conducted from the ministry of health perspective and 5% discounting was used for costs and benefits. In Canada (population=30 million), we estimate that each year there are 130,000 new cases of HZ, 17,000 cases of PHN and 20 deaths. Most of the pain and suffering is borne by adults over the age of 60 years and is due to PHN. Vaccinating 65-year-olds (HZ efficacy=63%, PHN efficacy=67%, no waning, cost/course=$150) is estimated to cost $33,000 per QALY-gained (90%CrI: 19,000-63,000). Assuming the cost per course of HZ vaccination is $150, probabilistic sensitivity analysis suggest that vaccinating between 65 and 75 years of age will likely yield cost-effectiveness ratios below $40,000 per Quality-Adjusted Life-Year (QALY) gained, while vaccinating adults older than 75 years will yield ratios less than $70,000 per QALY-gained. These results are most sensitive to the duration of vaccine protection and the cost of vaccination. In conclusion, results suggest that vaccinating adults between the ages of 65 and 75 years is likely to be cost-effective and thus to be a judicious use of scarce health care resources.




COMMENTARIES

Open Access Article

Novel vaccines and adjuvant systems: The utility of animal models for predicting immunogenicity in humans

Heather L. Davis
Pages 246 - 250
http://dx.doi.org/10.4161/hv.4.3.5318
Abstract | PDF

Animal models are essential for acquiring safety, immunogenicity and efficacy data to support the development of novel vaccines. However, extrapolating such results to designing human trials is challenging due to species-specific differences in responses to antigens, adjuvants, and pathogens. As well, most early vaccine work is conducted with in-bred mouse strains which may fail to uncover issues that could arise later in out-bred populations. Unlike drugs designed to be delivered systemically, vaccines work within a somewhat localized space, so allometric dose scaling to account for body size differences is not necessarily relevant. Comparison of immune responses and correlates of protection with a given antigen show widely variable results between animals and humans, even where protective immunity against challenge with the same pathogen can be studied. For adjuvants, it is possible to compare enhancement of immunogenicity compared to a non-adjuvant control vaccine. While some novel adjuvants provide similar levels of enhancement between species, others do not. It is also important to recognize the inter-relationship between antigens and adjuvants, since one can compensate for the other, masking particular effects. Despite all the limitations, animal immunogenicity and efficacy studies form an important part of pre-clinical development for novel vaccines, but considerable prudence is required when using and extrapolating results.

Open Access Article

Polio: The Indian sub-continent’s losing war

Mohammad A. Rai and Muhammad R. Nazir
Pages 251 - 252
http://dx.doi.org/10.4161/hv.4.3.5395
Abstract | PDF

The recent debate about 'effective control' rather than 'complete eradication' for polio has put the whole Global Polio Initiative into question. The implications for this are indeed daunting, more so for the Indian Sub-Continent, which hosts a huge chunk of the global polio load every year. The tremendous success achieved in combating polio during the previous decade in India and Pakistan is reason enough to continue on with the vaccination efforts. However, other subsidiary issues including social stigma and a weak infra-structure have also to be put into the eradication equation to meet the goal. The Sub-Continent stands at the cross-roads, and time is ripe now to formulate a multi-faceted strategy to eliminate this crippling disease from this part of the world, and consequently give a much-needed boast to global eradication efforts.