Table of Contents

Volume 6, Issue 4

  April 2010

  Pages 285 - 365

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 Issue Catalogue (MARC XML)

EDITOR'S CORNER

Open Access Article

Letter from the Editor

Ronald W. Ellis and Eva M. Riedmann
Page 285
http://dx.doi.org/10.4161/hv.6.4.11936
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NEWS & POLICY

Open Access Article

Lancet retracts controversial Autism Study

Eva M. Riedmann
Pages 286 - 291
http://dx.doi.org/10.4161/hv.6.4.11937
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Open Access Article

HPV vaccine predicted to slash cervical cancer rates

Eva M. Riedmann
Pages 286 - 291
http://dx.doi.org/10.4161/hv.6.4.11938
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Open Access Article

Immune-based strategy in Parkinson’s disease

Eva M. Riedmann
Pages 286 - 291
http://dx.doi.org/10.4161/hv.6.4.11939
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Open Access Article

New method makes vaccines stable at tropical temperatures

Eva M. Riedmann
Pages 286 - 291
http://dx.doi.org/10.4161/hv.6.4.11940
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Open Access Article

GreenVax Project

Eva M. Riedmann
Pages 286 - 291
http://dx.doi.org/10.4161/hv.6.4.11941
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Open Access Article

Advances in economics to further inform investments in vaccine development

Rena M. Conti
Pages 286 - 291
http://dx.doi.org/10.4161/hv.6.4.11942
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PORTRAIT OF A LEADING VACCINOLOGIST

Open Access Article

Towards a rational approach to vaccine development

Claude Leclerc
Pages 292 - 296
http://dx.doi.org/10.4161/hv.6.4.11878
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SPECIAL FOCUS REVIEWS

Open Access Article

Tuberculosis vaccine development :The development of a novel (preclinical) DNA vaccine

Masaji Okada and Yoko Kita
Pages 297 - 308
http://dx.doi.org/10.4161/hv.6.4.10172
Abstract | PDF

A third of the world’s population is infected with Mycobacterium tuberculosis, and 2 million people die from tuberculosis every year. The only tuberculosis vaccine currently available is an attenuated strain of Mycobacterium bovis BCG, although its efficacy against adult tuberculosis disease remains controversial. Furthermore multi-drug resistant tuberculosis is becoming big problems in the world. Therefore, the development of novel therapeutic vaccine as well as novel prophylactic vaccine against tuberculosis is required. This review provides a summary of novel vaccines (especially DNA vaccines) in preclinical stage using mouse, guinea pig and monkey models. In several promising novel vaccines, the studies were extended to a cynomolgus monkey model, which is currently the best animal model of human tuberculosis. The review also provides recent advances of the precise studies of induction of immunity including CD8 positive cytotoxic T cells and effector molecules such as granulysin by these vaccines, against multi-drug resistant tuberculosis and extremely drug resistant tuberculosis.

Open Access Article

Towards new tuberculosis vaccine

Stefan Svenson, Gunilla Källenius, Andrzej Pawlowski and Beston Hamasur
Pages 309 - 317
http://dx.doi.org/10.4161/hv.6.4.10711
Abstract | PDF

According to WHO, about one third of the world’s population is infected with bacteria of the Mycobacterium tuberculosis complex. Currently there is globally 9.15 million recorded cases of overt tuberculosis (TB) annually and due to lack of adequate diagnostics presumably a large but unknown number of non-recorded cases. TB is estimated to cause 1.65 million deaths per annum which accounts for one-fifth of all deaths by infectious diseases of adults in low-income countries. During recent years a rapid spread of multi-drug resistant bacteria causing about 0.5 million TB cases per year has worsened the problem. The live attenuated Bacillus Calmette-Guérin (BCG) vaccine which is the only currently available TB vaccine does not confer any significant protection against the most common and contagious form of TB – adult pulmonary TB.




RESEARCH PAPERS

Open Access Article

Safety and immunogenicity of a live attenuated varicella vaccine in VZV-seropositive HIV-infected adults

Adriana Weinberg, Myron J Levin and Rob Roy MacGregor
Pages 318 - 321
http://dx.doi.org/10.4161/hv.6.4.10654
Abstract | PDF

Background: Herpes-zoster is common in HIV-infected patients in spite of antiretroviral therapy. We evaluated the safety and immunogenicity of a live attenuated varicella-zoster virus (VZV) vaccine as a candidate for protecting HIV-infected adults against herpes-zoster. Methods: HIV-infected adults with CD4 ≥400 cells/µL and plasma HIV RNA <1000/mL were randomly assigned to receive two doses of VZV vaccine or placebo 12 weeks apart. HIV-uninfected age-matched controls also received two doses of vaccine. VZV-specific cell-mediated immunity (CMI) was measured at baseline and after vaccination using responder cell frequency (RCF), lymphocyte proliferation, and IFNγ ELISPOT. Results: Sixty-seven HIV-infected and 15 uninfected subjects, 18 to 65 years old, were enrolled. Adverse events were minor and similar in HIV-infected vaccine and placebo recipients. At 12 weeks after the 2nd dose of vaccine the magnitude of each measure of VZV CMI increased significantly in healthy controls. In HIV-infected vaccinees, VZV RCF significantly increased and ELISPOT showed a positive trend. None of VZV CMI measures significantly increased in HIV-infected placebo recipients. The immunogenicity of the vaccine did not correlate with the nadir CD4 cells of HIV-infected subjects. Conclusions: Two doses of varicella vaccine were safe in HIV-infected subjects with CD4 ≥400 cells/µL, but were only modestly immunogenic.

Open Access Article

Immunoprofiling toll-like receptor ligands: Comparison of immunostimulatory and proinflammatory profiles in ex vivo human blood models

Jennifer D. Hood, Hemamali J. Warshakoon, Matthew R. Kimbrell, Nikunj M. Shukla, Subbalakshmi S. Malladi, Xinkun Wang and Sunil A. David
Pages 322 - 335
http://dx.doi.org/10.4161/hv.6.4.10866
Abstract | PDF

There is a pressing need for the development of novel, safe, and effective adjuvants. The recent discovery and characterization of pathogen-associated molecular pattern (PAMP)-recognizing elements such as the Toll-like, NOD-like, and RIG-like receptors, has brought into sharp focus the role of PAMPs in bridging the innate and adaptive immune responses, and a detailed understanding of the immunostimulatory vis-à-vis proinflammatory activities could lead to the development of effective adjuvants, monophosphoryl lipid A being an excellent example. We describe in this paper a series of hierarchical assays that were employed to characterize TLR agonists in vitro including primary TLR-reporter assays, secondary indices of immune activation, and tertiary screens characterizing transcriptomal activation patterns to identify optimal immunostimulatory chemotypes. The evaluation of representative members of known human TLR agonists demonstrate that TLR2, -4, -5, and -7 agonists were immunostimulatory. TLR7 agonists were extremely immunostimulatory, stimulating nearly all subsets of lymphocytes without inducing proinflammatory cytokine responses. The TLR5 agonist, flagellin, while immunostimulatory, was also highly proinflammatory. These results suggest that TLR agonists other than lipid A-like chemotypes could be developed into potential adjuvants, and that this series of hierarchical assays could be adapted to rapidly identify in large libraries, compounds with adjuvantic potential that lack proinflammatory responses.

Open Access Article

Perception and acceptance of intradermal influenza vaccination: Patient reported outcomes from phase 3 clinical trials

Camille Reygrobellet, Muriel Viala-Danten, Juliette Meunier, Françoise Weber and Van Hung Nguyen
Pages 336 - 345
http://dx.doi.org/10.4161/hv.6.4.10753
Abstract | PDF

An intradermal trivalent inactivated influenza vaccine administered using a microinjection system has received European marketing authorization from the European Medicine Agency. We assessed clinical trial subjects' perception of injection site reactions (ISR) and whether ISR affected overall acceptability of vaccination and willingness to be vaccinated in the future. A validated, self-administered, patient reported outcome questionnaire was completed 21 days after intradermal or intramuscular vaccination by elderly and non-elderly adult participants in two European randomized, controlled, open-label phase 3 trials. The questionnaire addressed: the acceptability of ISR, effect of ISR on arm movement or sleep, satisfaction with the injection system, and willingness to be revaccinated. Questions were answered using a 5-point Likert verbal rating scale (1=most favorable, 5=most unfavorable response). Mean scores were calculated per group. 5305 questionnaires were completed and analyzed (95% return rate). Mean scores were close to 1 in all cases (maximum 1.68), indicating an overall favorable opinion of the vaccination and ISR. More than 96% of participants rated ISRs after intradermal or intramuscular vaccination as either 'totally acceptable' or 'very acceptable'. Willingness to get vaccinated the following year and satisfaction with the intradermal microinjection system or the conventional intramuscular syringe were high and were not adversely affected by ISR. ISR after intradermal influenza vaccine administered using a microinjection system are well accepted by the vaccinees and are generally not a cause for concern.

Open Access Article

Immunogenicity, large scale safety and lot consistency of an intradermal influenza vaccine in adults aged 18–60 years: Randomized, controlled, Phase III trial

Robert Arnou, Patrick Eavis, José-Ramon De Juanes Pardo, Arvydas Ambrozaitis, Marie-Pierre Kazek and Françoise Weber
Pages 346 - 354
http://dx.doi.org/10.4161/hv.6.4.10961
Abstract | PDF

Background: Vaccination is the most effective way of reducing the large health and economic burden of influenza, yet vaccination coverage remains low, particularly among non-elderly adults. Intradermal influenza vaccine produce an effective immune response and represents an alternative to intramuscular influenza vaccination. Methods: A Phase III multicentre, randomised, controlled, double-blind (for the three different lots of intradermal vaccine) study assessed lot-to-lot consistency, immunogenicity and safety of an intradermal inactivated trivalent split-virion influenza vaccine in 2255 adults aged 18–60 years. Participants received one of three lots of intradermal vaccine containing 9 µg of haemagglutinin per influenza strain, or a licensed intramuscular control vaccine containing 15 µg haemagglutinin/strain. Results: The three industrial lots of intradermal vaccine were equivalent in terms of post-vaccination titres elicited by day 21. The intradermal and intramuscular vaccines induced similar post-vaccination titres, and satisfied all three immunogenicity criteria set out in the European regulatory guidelines for influenza vaccines for each of the three influenza strains. The solicited systemic reaction profile and the incidence and type of spontaneously reported adverse events were similar in the two vaccine groups and in line with the known safety profile of inactivated influenza vaccines. Injection site reactions were more frequent with intradermal vaccination. Conclusions: This intradermal vaccine containing 9 µg per influenza strain, provides an alternative to conventional intramuscular vaccination, has a reliable production method and is equally immunogenic and well tolerated in adults. The study was registered at clinicaltrials.gov (identifier NCT00383539).




COMMENTARIES

Open Access Article

Development of TNFSF as molecular adjuvants for ALVAC HIV-1 vaccines

Jun Liu and Mario Ostrowski
Pages 355 - 359
http://dx.doi.org/10.4161/hv.6.4.10867
Abstract | PDF

A phase III clinical trial finished in Thailand recently showed that an ALVAC HIV-1 vaccine prime-gp120 protein boost vaccination regimen could modestly protect persons from HIV-1 infection, demonstrating that development of an effective and safe HIV-1 preventive vaccine is possible. ALVAC HIV-1 vaccines are candidate HIV-1 vaccines based on canarypox vectors. Previous clinical trials proved that ALVAC HIV-1 vaccines were safe but weak in immunogenicity when used in human subjects. We have been exploring to use tumor necrosis factor superfamily (TNFSF) members as adjuvants to enhance the immunogenicity of ALVAC HIV-1 vaccines. In this commentary, we will summarize our findings in using two TNFSF molecules, CD40L and OX40L, as adjuvants for an ALVAC HIV-1 vaccine in mouse model. We will also briefly discuss the challenges and prospects of using TNFSF molecules as adjuvants for HIV-1 vaccines in humans.

Open Access Article

Whole cell vaccination for meningococcus: Lessons from an idea whose time has gone

Joseph E. Labrie and Paul B. Keiser
Pages 360 - 365
http://dx.doi.org/10.4161/hv.6.4.11055
Abstract | PDF

Endotoxin in vaccines has long been recognized as a cause of adverse events and is generally regarded as a contaminant. However there are now a number of vaccine candidates that contain endotoxin as either antigen or adjuvant, particularly vaccines for Neisseria meningitidis based on native outer membrane vesicles (NOMV). Vaccines containing meningococcal endotoxin are not new. From 1907 to 1939 approximately 400,000 individuals were immunized with whole cell vaccines against meningococcus. We reviewed reports of meningococcal vaccinations from this period to characterize the adverse events to draw a baseline for evaluating meningococcal NOMV vaccines. The majority of these investigators conclude that whole cell vaccination was well tolerated with an adverse event profile comparable to other whole cell vaccines for Gram negative pathogens. There is insufficient data to draw conclusions on the duration of protection, if any, induced by whole cell meningococcal vaccines.