Table of Contents

Volume 5, Issue 12

  December 2009

  Pages 783 - 875

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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 783
PDF

Open Access Article

Human Vaccines: A home for policy

Eva M. Riedmann
Page 784
PDF




NEWS & POLICY

Open Access Article

US Government funds vaccine adjuvant development


Page 785
PDF

Open Access Article

Phase III study for NicVAX initiated


Page 785
PDF

Open Access Article

World’s largest malaria vaccine trial now underway


Pages 785 - 786
PDF

Open Access Article

Award: Best contract research organization


Page 786
PDF

Open Access Article

Federalize in haste: Repent at leisure

Henry I. Miller
Pages 787 - 788
Abstract | PDF

The federalization of private sector functions, including vaccine and drug development, has been proposed from time to time, but it is a bad idea. The history of government manufacture of pharmaceuticals and other products is far from encouraging, and where there are market failures that discourage the development of pharmaceuticals for rare or neglected diseases, there are various avenues other than federalization that can provide incentives to the private sector to fill the gap.

Open Access Article

Developing vaccines for bioterrorism: Incrementalism is not the answer

Robert House
Pages 788 - 789
PDF




PORTRAIT OF A LEADING VACCINOLOGIST

Open Access Article

Exploring the immunome: A brave new world for human vaccine development

Anne S. De Groot
Pages 790 - 793
PDF




SPECIAL FOCUS REVIEWS

Open Access Article

Botulinum Neurotoxin Vaccines:  Past history and recent developments

Janice M. Rusnak and Leonard A. Smith
Pages 794 - 805
Abstract | PDF

Botulinum toxin may cause a neuroparalytic illness that may result in respiratory failure and require prolonged mechanical ventilation.  As medical resources needed for supportive care of botulism in a bioterrorist event may quickly overwhelm the local healthcare systems, biodefense research efforts have been directed towards the development of a vaccine to prevent botulism.  While human botulism has been caused only by toxin serotypes A, B, and E (rarely serotype F), all seven known immunologically distinct toxin serotypes (A - G) may potentially cause intoxication in humans from a bioterrorist event.  A pentavalent (ABCDE) botulinum toxoid (PBT) has been administered as an investigation new drug (IND) to at-risk individuals for nearly 50 years.  Due to declining immunogenicity of the PBT, research efforts have been directed at development of both improved (less local reactogenicity) botulinum toxoids and recombinant vaccines as potential vaccine candidates to replace the PBT.

Open Access Article

Is new always better than old?  The development of human vaccines for anthrax

Leslie W Baillie
Pages 806 - 816
Abstract | PDF

Anthrax is caused by a Gram-positive aerobic spore-forming bacillus called  Bacillus anthracis. Although primarily a disease of animals, it can also infect man, sometimes with fatal consequences. As a result of concerns over the illicit use of this organism, considerable effort is focused on the development of therapies capable of conferring protection against anthrax. While effective concerns over the toxicity  of the current vaccines have driven the development of second-generation products.   Recombinant Protective Antigen (rPA), the nontoxic cell-binding component of anthrax lethal toxin,   is  the principal immunogen   of the vaccines currently undergoing human clinical trials.  While these new vaccines are likely to show reduced side effects they will still require  multiple needle based dosing  and the inclusion of the adjuvant alum which will make them expensive to administer and stockpile. To address these issues, researchers are seeking to develop vaccine formulations capable of  stimulating rapid protection following needle-free injection which are stable at room temperature to facilitate stockpiling and mass vaccination programs. Recent concerns over the potential use of  molecular biology to engineer vaccine resistant strains has prompted investigators to  identify  additional vaccine targets with which to extend the  spectrum of protection conferred by rPA.     While the injection of research dollars has seen a dramatic expansion of the anthrax vaccine field it is sobering to remember that work to develop the current second generation vaccines  began around the time of the first gulf war.  Almost two decades and millions of dollars latter we still do not have a  replacement vaccine  and  even when we do some  argue that the  spectrum of protection  that it confers will not be  as broad as the vaccine it replaces.   If we are to respond  effectively to emerging biological threats we need to develop  processes that generate protective vaccines in a meaningful time frame and yield products in months not decades !

Open Access Article

Plague vaccines and the molecular basis of immunity against Yersinia pestis

Lauriane E. Quenee and Olaf Schneewind
Pages 817 - 823
Abstract | PDF

Yersinia pestis is the causative agent of bubonic and pneumonic plague, human diseases with high mortality. Due to the microbe’s ability to spread rapidly, plague epidemics present a serious public health threat. A search for prophylactic measures was initially based on historical reports of bubonic plague survivors and their apparent immunity. Due to safety and efficacy concerns, killed whole-cell preparations or live-attenuated plague vaccines are no longer considered in the United States. Vaccine developers have focused on specific subunits of plague bacteria. LcrV, a protein at the tip of type III secretion needles, and F1, the capsular pilus antigen, are both recognized as plague protective antigens. Antibodies against LcrV and F1 interfere with Y. pestis type III injection of host cells. While LcrV is absolutely essential for Y. pestis virulence, expression of F1 is dispensable for plague pathogenesis in small animals, non-human primates and presumably also in humans. Several subunit vaccines, for example rF1+rV (rYP002), rF1V or rV10, are being developed to generate plague protection in humans. Efficacy testing and licensure for human use requires the establishment of correlates for plague immunity.

Open Access Article

Smallpox vaccines: New formulations and revised strategies for vaccination

Nir Paran and Gerd Sutter
Pages 824 - 831
Abstract | PDF

Smallpox has been eradicated but stockpiles of the causative infectious agent, variola virus, have been maintained over decades. Today, the threat of accidental or intentional poxvirus release is accompanied by the fact that the existing licensed smallpox vaccines cause rare but severe adverse reactions yet are the only products with approved efficacy against smallpox. New safer vaccines and new strategies of immunization are to be developed to fit to a scenario of emergency smallpox vaccination. However, we still lack knowledge about the pathogen and the mechanisms involved in acquiring protective immunity. Here, we review the history of smallpox vaccines and recent achievements in the development of highly efficacious and safer vaccines and vaccine applications. These include i) assessment of adequate animal models to study pathogenesis and protective immunity, ii) characterization of the immunity elicited by next generation vaccines, and (iii) the investigation of the requirements for rapidly protective vaccination.

Open Access Article

Vaccines against Tularemia

Eileen M. Barry, Leah Cole and Araceli E. Santiago
Pages 832 - 838
Abstract | PDF

Francisella tularensis is a Category A select agent for which vaccine and countermeasure development are a priority. In the past 8 years, renewed interest in this pathogen has led to the generation of an enormous amount of new data on both the pathogen itself and its interaction with host cells. This information has fostered the development of various vaccine candidates including acellular subunit, killed whole cell, and live attenuated. This review summarizes the progress and promise of these various candidates.




SHORT REPORT

Open Access Article

Patient's perceptions and information provided by the public health service are predictors for influenza vaccine uptake

Pilar Carrasco-Garrido, Ana López de Andrés, Valentín Hernández-Barrera, Ángel Gil de Miguel and Rodrigo Jiménez-García
Pages 839 - 842
Abstract | PDF

The objective of this study is to determine whether a patient's perception about, and information received from health services can be seen as predictive tools in regard to vaccination coverage against influenza.
Individual data from 7,341 adults included in the Madrid City Health Survey conducted in 2005 were used. With the objective of discovering the level of satisfaction with the public health system in mind, the question "In your opinion, does the public health care system in the city of Madrid work properly?" was asked to the population so as to obtain an affirmative/negative answer with respect to public health services. Overall influenza vaccination coverage was 24%. Logistic regression models indicate that the population more satisfied with as well as those who believe they are sufficiently informed by the health services are more likely to receive the vaccine against influenza (OR=1.23, 95% CI=1.06-1.43). Visits to a physician also constitute a statistically significant association.
Improving the perception with the public health system and the information provided to the population may help to increase influenza vaccination uptake.





RESEARCH PAPERS

Open Access Article

Prospective surveillance of varicella-zoster virus infections in an out-patient setting in Switzerland

Andrea Iseli, Christoph Aebi, Kurt Banz, Matthias Brunner, André M. Schmutz and Ulrich Heininger
Pages 843 - 846
Abstract | PDF

Limited data are available on the clinical impact of varicella in the ambulatory setting. Our goal was to determine real-life data on the clinical outcomes, medical management, and resource utilization in patients with varicella in Switzerland, a country without a universal immunization program against varicella. A total of 236 patients (222 = 94 % primarily healthy individuals) with a clinical diagnosis of varicella were recruited by pediatricians and general practitioners. Age range of patients was 0 - 47 years with a median of 5 years. The great majority of patients (179 = 76 %) were <6 years of age. 134 (57 %) patients were single cases and in the remaining 102 patients a total of 112 further cases of varicella occurred in their households. Of these, 17 (15 %) were primary cases, 18 (16 %) were coprimary cases, 75 (67 %) were secondary cases, and 2 cases (2 %) were not directly linked to the index case. A total of 29 complications were observed in 26 (11 %) of 236 patients, none of them with a known underlying disease and all subsided without apparent sequelae. All complications occurred in children under 12 years of age. In conclusion, this study describes the spectrum of varicella in an outpatient setting with a sizeable rate of complications and raises the question of the value of prophylactic immunization.

Open Access Article

Economic evaluation of varicella vaccination in Swiss children and adolescents

Kurt Banz, Andrea Iseli, Christoph Aebi, Matthias Brunner, André M. Schmutz and Ulrich Heininger
Pages 847 - 857
Abstract | PDF

This study explores the effects of three different 2-dose varicella zoster virus (VZV) vaccination strategies in Switzerland. The EVITA model was used to assess clinical benefits and costs of strategies 1) vaccination of 11-15 year old adolescents with a negative or uncertain history for chickenpox, 2) universal vaccination of toddlers at age 1 to 2 years, and 3) strategy 2 plus catch-up vaccination of 11-15 year old susceptible adolescents. The cost-effectiveness analysis compares strategies 2 and 3 versus strategy 1 (current vaccination policy in Switzerland). Probabilities for clinical outcomes and medical resource utilization were derived from a real-world survey among Swiss pediatricians and general practitioners including 236 individuals with VZV infection, published information on varicella complications, and expert opinion. Costs of medical resource utilization represent official Swiss medical tariffs. The model predicts both universal childhood vaccination strategies to be more effective in reducing varicella disease burden compared to strategy 1. Economically, both universal childhood vaccination strategies with or without catch-up result in net savings from the societal perspective reflected by a benefit cost ratio (BCR) of 1.22 or 1.29, respectively. In contrast, the model predicts net costs from the payer perspective (BCR of 0.27 and 0.30, respectively). These economic findings are comparable to those reported from other similar evaluations. However, due to the recent recommendation for using a 2-dose varicella vaccination schedule, our economic results for Switzerland are somewhat less favorable than those for other country analyses in which a less expensive 1-dose vaccination regimen for toddlers has been studied.

Open Access Article

Safety and immunogenicity of a tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine when co-administered with influenza vaccine in adults

Wayde M. Weston, Vijayalakshmi Chandrashekar, Leonard R. Friedland and Barbara Howe
Pages 858 - 866
Abstract | PDF

Annual vaccination with trivalent influenza vaccine (TIV), and a single dose of tetanus toxoid-reduced diphtheria toxoid-acellular pertussis (Tdap) vaccine, are both recommended for adults in the US. This study was conducted to obtain information on the safety and immunogenicity of co-administered TIV and a Tdap vaccine (Boostrix^®) in US adults. The immunogenicity and safety of Tdap and TIV was evaluated in 1497 adult subjects 19-64 years of age, who were randomized to receive Tdap and TIV either concomitantly or one month apart (TIV followed by Tdap). Seroprotection rates for diphtheria, tetanus and influenza antigens were high (≥94.1%) for both vaccine regimens, and immune responses to these antigens in the concomitant group were non-inferior to those observed in the sequential group. Although antibody concentrations for pertussis antigens were lower in the concomitant group than in the sequential group, concomitant administration was shown to be non-inferior to sequential administration with respect to anti-pertussis toxoid concentrations one month after Tdap vaccination. For filamentous haemagglutinin and pertactin, the between-group differences in antibody concentrations marginally exceeded pre-specified limits for defining non-inferiority. In both groups, anti-pertussis antibody concentrations were greater than those observed in infants following primary DTaP vaccination, in whom vaccine efficacy against pertussis was demonstrated .Reporting of adverse events appeared to be similar between groups. The data support the conclusion that Tdap and TIV vaccines may be co-administered without compromising either the effectiveness or tolerability of either vaccine.




COMMENTARIES

Open Access Article

Attenuated poxvirus vectors MVA and NYVAC as promising vaccine cadidates against HIV/AIDS

Mariano Esteban
Pages 867 - 871
Abstract | PDF

As yet, the only human infectious disease eradicated from our planet is smallpox, caused by variola virus a member of the poxvirus family. The vaccination success, with the declaration by WHO in 1980 of a worldwide free of smallpox, was largely due to the availability of a quite effective and stable live vaccine, as well as the restricted human host for virus infection. Variola was considered one of the most devastating diseases of human mankind. With the sudden appearance of the HIV/AIDS in 1981, an infection which spread rapidly to become a pandemic in a short time, causing up to date more than 22 million deaths, about 40 million people infected and a current incidence of about 3 million deaths per year, this dreadful pandemic has become one of the most severe diseases in the World, specially in poor countries. While different antiviral drugs have been developed that block virus replication at various stages of infection, however the rapid virus escape that follows during the drug therapy due to mutations, makes the development of vaccines the most secure option to control and eradicate the disease. Numerous vaccines have been developed, but to date the clinical trials have failed to show any efficacy against HIV infection. Due to the proven success of vaccinia virus in the control of smallpox as well as of poxvirus recombinants against veterinary diseases, a major effort has been directed to document the advantages of poxvirus vectors as vaccines against multiple diseases. Two of the most promising poxvirus vectors are the highly attenuated  modified vaccinia virus Ankara (MVA) and the modified Copenhagen strain NYVAC. In this commentary I describe the biological characteristics of the attenuated poxvirus vectors, MVA and NYVAC, with emphasis in their application in HIV preclinical and clinical trials, and considerations as future HIV vaccines.

Open Access Article

Why is a protective antigen protective?

Louise J. Gourlay, Giorgio Colombo, Marco Soriani, Guido Grandi, Xavier Daura and Martino Bolognesi
Pages 872 - 875
Abstract | PDF

One of the major challenges in vaccine development is the identification of microbial components that give rise to a protective immune response. Over the last decade,  genome and proteome-based methods have proven successful in discovering new vaccine candidates for many pathogens through the selection of secreted or surface-exposed protein antigens and their screening in proper biological assays. However, these approaches still require intensive research activities to single out, among the large number of secreted and surface exposed proteins those very few which are protective. The question of which structural properties render an antigen capable of eliciting the production of functional remains most challenging. In such scientific and methodological context, the EU-funded project BacAbs was set up in 2007 with the main objective of developing a knowledge-based protocol able to discern protective from non-protective protein antigens, based on their amino acid sequences and molecular properties. The successful BacAbs multidisciplinary approach is highlighted by the recent analysis of three antigens from two diverse pathogens. Here, we describe the work and results carried out so far by the BacAbs Consortium, and discuss its relevance with regards to accelerating antigen selection processes and state-of-the-art vaccine development.