Table of Contents

Volume 6, Issue 12

  December 2010

  Pages 955 - 1075

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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 955
http://dx.doi.org/10.4161/hv.6.12.14468
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NEWS, POLICY AND PROFILES

Open Access Article

News

Eva Maria Riedmann
Pages 956 - 958
http://dx.doi.org/10.4161/hv.6.12.14483
Abstract | PDF

Sanofi Pasteur’s dengue vaccine enters Phase III trials
Negative news coverage erodes public support for mandatory HPV vaccine
GlobeImmune’s therapeutic HCV vaccine increases Sustained Virologic Response
New consortium designs human trials of mosaic HIV vaccine
New Center for Systems Vaccinology
Novartis and Venter collaborate to develop next generation vaccines
Cancer Research UK funds brain cancer vaccine trial
 

Open Access Article

Next generation of therapeutic cancer vaccines require smart vaccine design

Marc Mansour
Pages 959 - 961
http://dx.doi.org/10.4161/hv.6.12.14484
PDF

Open Access Article

Questions for Biotechs: AERAS

Jim Connolly
Pages 962 - 963
http://dx.doi.org/10.4161/hv.6.12.14485
PDF




MEETING REPORTS

Open Access Article

Phacilitate, Barcelona Vaccine Forum 2010: Focus on correlates of protection against influenza

Ernst C. Soethout, Wilfried A.M. Bakker, Roeland H. van Dam, Nynke Y. Rots and Claire J. Boog
Pages 964 - 965
http://dx.doi.org/10.4161/hv.6.12.13218
Abstract | PDF

The success of vaccination has been evidently shown, e.g. in the eradication of smallpox. However, vaccine development and registration has become increasingly challenging as definite parameters of efficacy are often lacking. One of the reasons is that, in contrast to treatment of overt disease through medication, prevention of disease by vaccines is difficult to measure. This is specifically evident with the introduction of a vaccine targeting a relatively uncommon infection such as induced by Meningococci C. The efficacy of this vaccine was finally determined only after large scale introduction in the UK as in the Netherlands since the number of clinical infections was too low to determine efficacy in clinical trials. Even for frequent pathogens such as influenza the protective effect of vaccination is sometimes questioned in the absence of clear parameters of protection. Here, ethical considerations prevent a double blind placebo-controlled trial that should enable an unambiguous insight. As a whole, the identification and usage of valid parameters of efficacy indicating protection is essential for vaccine development and registration. The introduction of these so-called correlates of protection (COP) is therefore essential. At the Phacilitate Barcelona Vaccine Forum 2010, identification of new COP for vaccines was a recurring focus of discussion, specifically for vaccines against influenza, and essential observations were made to advance its development.

Open Access Article

A key for successful development of flu vaccines: Public-private collaboration - the Barcelona Vaccine Forum, Phacilitate, the Fira Palace Barcelona Spain, 21-23 June, 2010, the meeting report

Cristina Niculescu and Jean-Marc Balloul
Pages 966 - 969
http://dx.doi.org/10.4161/hv.6.12.13353
Abstract | PDF

At the Barcelona Vaccine Forum, Phacilitate 2010, numerous plenary sessions, round table discussions, and workshops were dedicated to discussions surrounding one major topic, i.e. ensuring flu vaccine availability in a pandemic situation. High level speakers and participants coming from different horizons (WHO, US-FDA, EU-EMA, vaccine industry, etc ) shared their experience encountered during the influenza pandemic from 2009, the strategies and actions undertook for accelerating pandemic flu vaccines development and approval, the cooperation and coordination activities deployed to overcome the shortage for such vaccine, encountered especially in developing countries. During other sessions, the speakers highlighted the role of innovative partnering, business models or funding opportunities in enabling vaccine market development on a global scale. Finally, novel approaches and technologies for vaccines production that respond better to the growing worldwide demand for influenza vaccine and the achievements with the development of an “universal” vaccine that could guard against all seasonal and pandemic influenza strains were presented during the Barcelona Forum.




PRODUCT REVIEW

Open Access Article

Recombinant Bet v 1 vaccine for treatment of allergy to birch pollen

Hans Grönlund and Guro Gafvelin
Pages 970 - 977
http://dx.doi.org/10.4161/hv.6.12.13348
Abstract | PDF

Therapeutic vaccination is the only disease modifying allergy treatment. Recombinant allergen vaccines represent defined component vaccines and are advantageous compared to allergen extract vaccines because of their well defined and measurable allergen content. As the major birch pollen allergen Bet v 1 is the dominant disease-eliciting allergen in birch pollen Bet v 1 vaccines based on GMP produced recombinant (r)Bet v 1 have been developed for treatment of birch pollen allergic patients. Three vaccines comprising hypoallergenic rBet v 1 derivatives have in clinical trials been shown to improve allergic symptoms and to favourable modify the immune response to Bet v 1. In a phase II trial, vaccination with rBet v 1 resulted in reduced rhinoconjunctivitis symptoms and rescue medication compared to placebo. Vaccination with rBet v 1 formulated as tablets for sublingual administration revealed clinical relevant efficacy in rhinoconjunctivitis patients. The positive results imply that rBet v 1 vaccines constitute a therapeutic alternative for birch pollen allergic patients.




REVIEWS

Open Access Article

Mucosal immunization: A realistic alternative

Diana C. Otczyk and Allan W. Cripps
Pages 978 - 1006
http://dx.doi.org/10.4161/hv.6.12.13142
Abstract | PDF

Most infections occur at or through mucosal surfaces. Despite this knowledge, current vaccination practices rely predominantly on parenteral administration with only a few vaccines being registered for administion by the mucosal route. Whilst mucosal immunization brings many advantages, the lack of reliable delivery systems has been a major drawback to date. With the recent advances in delivery system technology and the improved understanding of site specific mucosal immune mechanisms, mucosal immunization offers an exciting alternative vaccination strategy.

Open Access Article

First in humans: A new molecularly defined vaccine shows excellent safety and strong induction of long-lived Mycobacterium tuberculosis-specific Th1-cell like responses

Tom H. M. Ottenhoff, T. Mark Doherty, Jaap T. van Dissel, Peter Bang, Karen Lingnau, Ingrid Kromann and Peter Andersen
Pages 1007 - 1015
http://dx.doi.org/10.4161/hv.6.12.13143
Abstract | PDF

Tuberculosis (TB) remains a major killer worldwide. The only available TB-vaccine, the nearly century-old Mycobacterium bovis BCG, has had only a limited effect on TB incidence. Therefore, developing new TB vaccines is a key priority, and the first new generation TB vaccines are now being tested in clinical trials. Here we describe the development and first testing in humans of a novel, wholly synthetic TB subunit vaccine. This vaccine has proven safe and highly immunogenic in all species in which it was tested, including mice, guinea pigs, non-human primates and humans. Most encouragingly, following vaccination in humans, strong IFN-γ responses persisted through at least 2½ years of follow-up, indicating induction of a substantial memory response by this new TB vaccine. These findings encourage further preclinical and clinical studies with TB subunit vaccines and cellular immunity-stimulating new adjuvants.

Open Access Article

Could the United States experience rubella outbreaks as a result of vaccine refusal and disease importation?

Brynn E. Berger and Saad B. Omer
Pages 1016 - 1020
http://dx.doi.org/10.4161/hv.6.12.13398
Abstract | PDF

Prenatal rubella infection early in gestation is likely to damage the fetus, leading to miscarriage, stillbirth, neonatal death, or congenital rubella syndrome (CRS). CRS is a devastating syndrome that encompasses a wide variety of disorders, including (but certainly not limited to) cataracts, congenital heart defects, deafness, and mental retardation. Elimination of rubella was declared in the United States in 2004; however, the US faces the risk of rubella outbreaks. In this article, we discuss the possibility of rubella outbreaks in the US due to refusal of measles-mumps-rubella (MMR) vaccination and importation of the disease from regions where vaccination coverage is suboptimal. To avoid the severe health consequences associated with prenatal rubella infection, continued attention should be given to the maintenance of high MMR coverage.




SHORT REPORTS

Open Access Article

A policy framework for accelerating adoption of new vaccines

Orin S. Levine, Rana Hajjeh, John Wecker, Thomas Cherian, Katherine L. O’Brien, Maria Deloria Knoll, Lois Privor-Dumm, Hans Kvist, Angeline Nanni, Allyson P. Bear and Mathuram Santosham
Pages 1021 - 1024
http://dx.doi.org/10.4161/hv.6.12.13076
Abstract | PDF

Rapid uptake of new vaccines can improve health and wealth and contribute to meeting Millennium Development Goals. In the past, however, the introduction and use of new vaccines has been characterized by delayed uptake in the countries where the need is greatest. Based on experience with accelerating the adoption of Hib, pneumococcal and rotavirus vaccines, we propose here a framework for new vaccine adoption that may be useful for future efforts. The framework organizes the major steps in the process into a continuum from evidence to policy, implementation and finally access. It highlights the important roles of different actors at various times in the process and may allow new vaccine initiatives to save time and improve their efficiency by anticipating key steps and actions.

Open Access Article

Young-adult carriers of Neisseria meningitidis in Puglia (Italy): Will the pattern of circulating meningococci change following the introduction of meningococcal serogroup C conjugate vaccines?

Cinzia Germinario, Silvio Tafuri, Christian Napoli, Maria Teresa Montagna, Maria Teresa Balducci, Francesca Fortunato, Domenico Martinelli and Rosa Prato
Pages 1025 - 1027
http://dx.doi.org/10.4161/hv.6.12.13145
Abstract | PDF

Studies of meningococcal carriage are essential in improving knowledge of the epidemiology of meningococcal disease. The aim of this study is to ascertain the carrier rate and the serogroups of Neisseria Meningitidis circulating in a sample of students from the University of Bari. The population consisted of university students from the University of Bari - School of Medicine, who were invited to take a nasopharyngeal swab. The swabs were plated on selective plate medium; cultural and MLST tests were performed. Of 583 university students 12 carriers were identified (2%). 9 isolates proved auto-agglutinable. The other strains belonged to serogroups B, W135 and Y. Auto-agglutinable strains belonged to different clonal complexes, of which ST-53 was the most common. Only one strain, that belonged to ST-23/cluster A3 clonal complex, could cause meningococcal disease. No type C serogroup strain was detected and this could be directly related to immunization policies that provided meningococcal serogroup C conjugate vaccines for newborns and adolescents. The changing pattern of circulating serogroups of Neisseria meningitidis in healthy carriers could support a new immunization strategy which could provide quadrivalent meningococcal conjugate vaccines to pre-adolescents and adults.




RESEARCH PAPERS

Open Access Article

Optimized development of a candidate strain of inactivated EV71 vaccine and analysis of its immunogenicity in rhesus monkeys

Chenghong Dong, Jingjing Wang, Longding Liu, Hongling Zhao, Haijing Shi, Ying Zhang, Li Jiang and Qihan Li
Pages 1028 - 1037
http://dx.doi.org/10.4161/hv.6.12.12982
Abstract | PDF

Enterovirus type 71 (EV71) is one of the main etiologic agents responsible for periodic epidemics of hand-foot-and-mouth disease (HFMD). The prevention and control of EV71 epidemics with effective anti-viral agents and vaccines is very important for public health. Because the pathogenesis of EV71 in the human body is not completely clear and genetic variations in the virus during its replication are difficult to control, we have focused on the development of an inactivated whole-virus vaccine. In this study, we screened 16 strains isolated from different areas of China and selected one strain for the development of an inactivated EV71 vaccine. The results of our study suggest that the FY-23K-B strain, which is a candidate strain for an EV71 inactivated vaccine, satisfied the requirements of vaccine production in terms of genetic stability, biological activity, and good immunogenicity. The experimentally inactivated vaccine produced using this strain was capable of inducing an immune response and offered protection to rhesus monkeys against future virus attacks.

Open Access Article

Long term immunity to live attenuated Japanese encephalitis chimeric virus vaccine: Randomized, double-blind, 5-year phase II study in healthy adults

Peter E. Nasveld, Andrew Ebringer, Nathan Elmes, Sonya Bennett, Sutee Yoksan, John Aaskov, Karen McCarthy, Niranjan Kanesa-thasan, Claude Meric and Mark Reid
Pages 1038 - 1046
http://dx.doi.org/10.4161/hv.6.12.13057
Abstract | PDF

In a randomized, double-blind study, 202 healthy adults were randomized to receive a live, attenuated Japanese encephalitis chimeric virus vaccine (JE-CV) and placebo 28 days apart in a cross-over design. A subgroup of 98 volunteers received a JE-CV booster at month 6. Safety, immunogenicity, and persistence of antibodies to month 60 were evaluated.

There were no unexpected adverse events (AEs) and the incidence of AEs between JE-CV and placebo were similar. There were three serious adverse events (SAE) and no deaths. A moderately severe case of acute viral illness commencing 39 days after placebo administration was the only SAE considered possibly related to immunization. 99% of vaccine recipients achieved a seroprotective antibody titer ≥ 10 to JE-CV 28 days following the single dose of JE-CV, and 97% were seroprotected at month 6. Kaplan Meier analysis showed that after a single dose of JE-CV, 87% of the participants who were seroprotected at month 6 were still protected at month 60. This rate was 96% among those who received a booster immunization at month 6. 95% of subjects developed a neutralizing titer ≥ 10 against at least three of the four strains of a panel of wild-type Japanese encephalitis virus (JEV) strains on day 28 after immunization. At month 60, that proportion was 65% for participants who received a single dose of JE-CV and 75% for the booster group. These results suggest that JE-CV is safe, well tolerated and that a single dose provides long-lasting immunity to wild-type strains.

Open Access Article

A subunit vaccine based on biodegradable microspheres carrying rHsp65 protein and KLK protects BALB/c mice against tuberculosis infection

Sandra Aparecida dos Santos, Carlos Rodrigo Zárate-Bladés, Fábio Cícero de Sá Galetti, Izaíra Tincani Brandão, Ana Paula Masson, Edson Garcia Soares, Ana Paula Ulian Araújo and Celio Lopes Silva
Pages 1047 - 1053
http://dx.doi.org/10.4161/hv.6.12.13350
Abstract | PDF

Of the hundreds of new tuberculosis (TB) vaccine candidates, some have therapeutic value in addition to their prophylactic properties. This is the case for the DNA vaccine encoding heat-shock protein 65 (DNAhsp65) from Mycobacterium leprae. However, there are concerns about the use of DNA vaccines in certain populations such as newborns and pregnant women. Thus, the optimization of vaccination strategies that circumvent this limitation is a priority. This study evaluated the efficacy of a single dose subunit vaccine based on recombinant Hsp65 protein against infection with M. tuberculosis H37Rv. The Hsp65 protein in this study was either associated or not with immunostimulants, and was encapsulated in biodegradable PLGA microspheres. Our results demonstrate that the protein was entrapped in microspheres of adequate diameter to be engulfed by phagocytes. Mice vaccinated with a single dose of Hsp65-microspheres or Hsp65+CpG-microspheres developed both humoral and cellular-specific immune responses. However, they did not protect mice against challenge with M. tuberculosis. By contrast, Hsp65+KLK-microspheres induced specific immune responses that reduced bacilli loads and minimized lung parenchyma damage. These data suggest that a subunit vaccine based on recombinant protein Hsp65 is feasible.

Open Access Article

Correlation between levels of human papillomavirus (HPV)-16 and 18 antibodies in serum and cervicovaginal secretions in girls and women vaccinated with the HPV-16/18 AS04-adjuvanted vaccine

Tino F. Schwarz, Mariëlle Kocken, Tiina Petäjä, Mark H. Einstein, Marek Spaczynski, Jacqueline A. Louwers, Court Pedersen, Myron J. Levin, Toufik Zahaf, Sylviane Poncelet, Karin Hardt, Dominique Descamps and Gary Dubin
Pages 1054 - 1061
http://dx.doi.org/10.4161/hv.6.12.13399
Abstract | PDF

This pooled analysis of data from four Phase III clinical trials was undertaken to assess the correlation between levels of anti-human papillomavirus (HPV)-16/18 antibodies in serum and cervicovaginal secretions (CVS) in girls and women vaccinated with the HPV-16/18 AS04-adjuvanted vaccine. Serum and CVS samples were collected from a subset of women aged 10–65 years (N=350) at pre-specified time-points from 7 to 36 months post-vaccination. Anti-HPV-16/18 antibody levels in serum and CVS were measured by enzyme-linked immunosorbent assay. Pearson correlation coefficients between serum and CVS antibody levels, standardized for total immunoglobulin G, were calculated at each time-point in women with detectable antibodies in both serum and CVS. All subjects had seroconverted at Month 7 and remained seropositive through Month 36 for both antigens. Geometric mean titers of anti-HPV-16/18 antibodies in serum were substantially higher at all time-points than those in a control group of women who had cleared a natural HPV infection in another trial. In women with detectable antibodies in both serum and CVS, good correlation was seen between HPV-16/18 antibody levels at all time-points (Pearson correlation coefficient: 0.84–0.92 for HPV-16 and 0.90–0.91 for HPV-18). The strong correlation between levels of HPV-16/18 antibodies in serum and CVS up to 36 months post-vaccination in girls and women vaccinated with the HPV-16/18 AS04-adjuvanted vaccine supports transudation of serum antibodies as the mechanism by which antibodies are introduced into CVS. These CVS antibodies may play a role in the protective efficacy of this vaccine.




COMMENTARIES

Open Access Article

Herpesvirus vaccines: Challenges and future prospects

Corey Smith and Rajiv Khanna
Pages 1062 - 1067
http://dx.doi.org/10.4161/hv.6.12.13347
Abstract | PDF

Human herpes viruses are a family of large double stranded DNA viruses. Their life-cycle is characterized by an initial lytic cycle of infection in which large numbers of new virions are generated, followed by a pattern of lifelong latent infection with intermittent reactivation and viral shedding. Co-evolution over millennia has resulted in an interaction between host and pathogen which leads to the successful establishment of a lifelong latent infection with typically minimal impact upon the host, and subsequent maintenance and control of latently infected cells by the host immune system. Infection is usually asymptomatic or leads to an acute transient disease. However more severe disease can arise during primary infection, latency or upon reactivation; in both an immunocompromised and an immunocompetent setting, indicative of a need for the development of vaccine strategies which can either prevent infection or treat virally-associated diseases.

Open Access Article

Searching for the Holy Grail of a staphylococcal vaccine

Isaac Thomsen, Hannah Dudney and C. Buddy Creech
Pages 1068 - 1070
http://dx.doi.org/10.4161/hv.6.12.12917
Abstract | PDF

The pursuit of an effective staphylococcal vaccine has never been more critical, as community-associated MRSA has become the most common bacterial infection in the US. In this commentary, we will highlight new discoveries in the host response to colonization and infection with S. aureus, discuss potential antigens that might be used as vaccines, and make recommendations as to how the field can move forward towards discovering the "holy grail" of an effective staphylococcal vaccine.

Open Access Article

The threat of vaccine associated poliomyelitis in India: Medicolegal issues involved

Meena Rajput and Luv Sharma
Pages 1071 - 1075
http://dx.doi.org/10.4161/hv.6.12.13354
Abstract | PDF

India is among the world’s large reservoirs of wild poliovirus (WPV) with 559 confirmed cases of poliomyelitis (wild virus) being reported in 2008. The World Health Organization’s program for the eradication of poliomyelitis in third world countries like India is associated with major ethical and medico-legal implications. Two vaccines are available in India for poliomyelitis i.e. oral polio vaccine (OPV) and inactivated polio vaccine (IPV), of which OPV is used in the eradication campaign, the case count for 2009 being 36 out of a total of 384 reported cases globally, the case count for mid 2010 being 19 cases out of 84 reported globally. There are widespread reports of vaccine derived poliomyelitis as well as vaccine associated poliomyelitis (VAP) from different parts of the country, which can be linked to resurgence of polio in several states or to the failure of the polio drive (Polio Sundays). Though an extended comprehensive polio campaign is on and both money and manpower are being dumped for achieving the goal of polio eradication, the ground reality is entirely different. The argument that wild polio strains have surfaced to hamper the drive cannot account for all post vaccination cases. The Indian Academy of Paediatrics has forcefully suggested replacement of OPV by IPV, as the effectiveness of IPV far exceeds the cost benefit of OPV. IPV has by and large replaced OPV in many parts of the world. The second issue is the threat of litigation on the health department once the post vaccination cases rise even further. There are certain other socio-ethical issues discussed in this paper on a subject which has an important bearing on the health statistics of this country.