Table of Contents

Volume 5, Issue 10

  October 2009

  Pages 647 - 719

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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 647
http://dx.doi.org/10.4161/hv.5.10.9928
PDF

Open Access Article

World Vaccine Congress Washington 2009: Editor's note

Eva Riedmann
Page 648
http://dx.doi.org/10.4161/hv.5.10.9930
PDF




WVC 2009: MEETING REPORTS

Open Access Article

The U.S. vaccine and immunization enterprise:  Working to sustain and foster vaccine innovation

Angela K. Shen
Pages 649 - 653
http://dx.doi.org/10.4161/hv.5.10.9215
Abstract | PDF

The U.S. vaccine and immunization enterprise has been successful in introducing new vaccines to the U.S. and global markets.  The vaccine sector of the pharmaceutical industry is experiencing growth projected to increase through the next decade.  Despite the successes and future promise, challenges exist for funding the research and development and delivery of new vaccines.  Adult and adolescent vaccination coverage of routinely recommended vaccines remains low and financial barriers to vaccination have emerged due to the increased cost of vaccination including the increased price of newer vaccines.  Because the development and manufacture of new vaccines rely on the sales of established vaccines and other products, high coverage rates are important to the vaccine industry.  Moreover, government and foundation support can assist in the research and development and introduction of new vaccines, especially for those vaccines that are necessary for use in the developing world.  Novel approaches are needed to encourage and expand partnerships to advance vaccine research and development.  Manufacturers in emerging economies have an increasing role in providing innovative vaccines to the world.

Open Access Article

Taking aim at novel vaccines market

Sita Awasthi
Pages 654 - 657
http://dx.doi.org/10.4161/hv.5.10.9171
Abstract | PDF

The World Vaccine Congress Washington 2009 was held in Chantilly, VA USA April 2O -23rd. The Vaccine congress attracted over 400 participants from across the world, including leading vaccine manufacturers, biotechs, governmental agencies, NGOs, research and academic institutes, venture capital and legal firms, contract service and equipment manufacturers. The speakers covered a wide range of topics, including the role of government and regulatory agencies, funding availability,   research and development, manufacturing, packaging and post vaccine evaluations. Past vaccine development efforts have historically focused on infectious diseases. With advancements in the field of immunology, molecular biology and vaccinology, the vaccine field has begun moving in new directions. “Taking aim at novel vaccines market” session chaired by Dr. Una Ryan, Chief Executive Officer of Waltham Technologies, was focused on traditional approaches to novel targets (nosocomial infections), novel approaches to traditional targets (flu and rabies), novel approaches to novel targets (Type 1 diabetes, multiple sclerosis and smoking) and vaccines for developing markets (TB, malaria, rabies). The importance of collaborations among academic institutions, industries, and philanthropic foundations for developing markets was also emphasized.

Open Access Article

Focus on Influenza vaccines

Nikolai Petrovsky
Pages 658 - 659
http://dx.doi.org/10.4161/hv.5.10.9315
Abstract | PDF

US Government Influenza Vaccine Initiatives
Mike Perdue (HHS) discussed HHS mandates covering pandemic flu. Funds have been used for advanced development, stockpile acquisitions and infrastructure development. Current major programs include stockpiling of H5N1, cell-based influenza vaccine development, antigen-sparing technology, recombinant vaccine development and building US domestic manufacturing capacity. He identified program problems as efficacy trials being hampered by unpredictable influenza infection rates year to year, comparisons of egg and cell-derived vaccines being complicated by the fact that the seed stock is egg derived, and FDA concerns about consequences of producing live vaccine in permanent cell lines. Recent initiatives including mix and match clinical trials where NIH has tested different manufacturers antigens (GSK and Novartis) with each other's adjuvants (MF59 and AS03). The audience raised concerns that no trials of pandemic vaccine were being conducted in children, but he explained this was not something that HHS could influence but was in the hands of the companies developing the vaccines. BARDA has built a pandemic H5N1 antigen stockpile of 20 million doses and has also purchased 5 million adjuvant doses. BARDA would like to see an increased uptake of use of seasonal flu vaccines to stimulate extra US manufacturing capacity that could provide surge capacity in event of a pandemic.

Open Access Article

Targeting biodefense markets

Gene Garrard Olinger Jr.
Pages 660 - 665
http://dx.doi.org/10.4161/hv.5.10.9265
Abstract | PDF

The “World Vaccine Congress 2009” held in Washington D.C. (April 20-23, 2009) sponsored several sessions focused on the vaccine market targeting biodefense.  On day one of the congress, a panel discussion outlined the federal progress in medical countermeasure preparedness that included emerging infections, influenza, and biodefense focuses.  The second day, a session focused on the biodefense vaccine market with both government and industry members discussing the opportunities and challenges associated with the budding market.

Open Access Article

Cancer vaccines and immunotherapy

Haiwen Tang
Page 666
http://dx.doi.org/10.4161/hv.5.10.9132
PDF

Open Access Article

Adjuvants and delivery technologies

Kevin Killeen
Pages 667 - 670
http://dx.doi.org/10.4161/hv.5.10.9140
Abstract | PDF

The 2009 World Vaccine Congress (WVC) meeting was held in Chantilly, VA from April 20-23.  This is a summary of the ‘Adjuvant and Delivery Technologies’ session chaired by Dr. William Warren of VaxDesign.
The WVC ‘Adjuvants and Delivery Technologies’ session consisted of three oral presentations and a panel set of presentations followed by discussion.  The oral presenters were Dr. Christian Mandl, Head of Research & Global Head, Viral Vaccine Projects, Novartis, Dr. James Baker, CEO and CSO, NanoBio, and Dr. Geert Vanden Bossche, Senior Program Officer, Global Health Discovery, Bill and Melinda Gates Foundation.  The panel discussion topic was ‘TLR-dependent and TLR-independent adjuvant candidates in clinical development’ consisting of panelists Dr Danilo Casimiro, Merck, Ms. Debbie Drane, CSL, Dr. Nikolai Petrovsky, Vaxine, and Dr Yuichiro Satoh, BioMedCore. 





REVIEW

Open Access Article

Different spectra of therapeutic vaccine development against HPV infections

Azam Bolhassani, Elham Mohit and Sima Rafati Rafati
Pages 671 - 689
http://dx.doi.org/10.4161/hv.5.10.9370
Abstract | PDF

Human papillomaviruses (HPVs) are simple, non-enveloped, double-stranded DNA viruses and responsible for an enormous global burden of genital disease. HPV is annually associated with 500,000 new cases of cervical cancer and 250,000 cervical cancer deaths worldwide. The association between HPV infection and cervical cancer indicates that HPV serves as an ideal target for development of preventive and therapeutic vaccines. A novel approach for primary prevention of cervical cancer has become available by the discovery of efficient prophylactic HPV vaccines based on virus-like particles. Therapeutic vaccination has been limited by inadequate antigen-specific immune responses. Different therapeutic strategies have been developed including peptide immunization-based therapies, DNA vector-based therapies, viral/ bacterial vector-based therapies, immune response modifiers, Photodynamic therapy (PDT) and T cell receptor based therapy. At present, the design of therapeutic vaccines to control the growth of HPV-induced tumors has focused on utilization of E6 and E7 proteins or peptides, as vaccine antigens. Human trials are the most important test for the efficacy of HPV16/18 E6 and E7 proteins as immunotherapy for cervical cancer. This review attempts to describe different therapeutic vaccinations against HPV infections.




RESEARCH PAPERS

Open Access Article

Tuberculin conversion and leukocyte migration inhibition test after BCG vaccination in newborn infants

MMA Faridi, Sarvpreet Kaur, Sriram Krishnamurthy and Pramod Kumari
Pages 690 - 695
http://dx.doi.org/10.4161/hv.5.10.9317
Abstract | PDF

Background: There are reports that BCG vaccine take-up may be delayed or poor among preterm and low birth weight babies Objective: The present study was conducted with the objective of (a) studying BCG take-up through tuberculin conversion by Mantoux test at 12 weeks and 6 months of age in babies vaccinated with BCG at birth and (b) evaluating the Leukocyte Migration Inhibition Test (LMIT) in BCG vaccinated babies who did not react to Mantoux test. Design: Prospective observational study.  Methods:  BCG vaccine was administered to 143 neonates of 31-41 weeks gestation within 7 days of birth. At 12 weeks of age, Purified Protein Derivative (1 TU PPD-RT 23 with Tween 80) was injected to all the babies and induration was measured at the injection site after 48 hours. Mantoux negative babies were subjected to the LMIT. All the Mantoux test and LMIT negative babies were followed up and given another Mantoux test at 6 months. Those babies who showed a negative Mantoux test at 6 months and negative LMIT at 12 weeks were subjected to another LMIT at 6 months. Results: Local BCG reaction was exhibited by 95.5% babies at 8 weeks and scar formed in 47.2% of them by 12(+1) weeks. The tuberculin conversion rate after 12 weeks of BCG vaccination was 42.7%. The rate of tuberculin conversion was significantly more in babies with birth weight > 2500 g as compared to low birth weight babies. Also, the rate of tuberculin conversion was significantly more in term infants as compared to preterm babies.  Six months after BCG vaccination, 41.5% of previously Mantoux negative babies showed tuberculin conversion. Overall, 66.4% babies reacted to PPD after 6 months. LMIT was positive in 84.1% babies who had a negative Mantoux test at 12 weeks. Six months after BCG vaccination, 53.8% of babies who had LMIT negative at 3 months became LMIT positive. Thus out of 143 babies, 95.8% had either a reactive Mantoux test or positive LMIT  6 months after BCG vaccination. There were only 6 babies (4.2%) who did not show adequate responses to BCG vaccination. Conclusion: Preterm babies of 31 to 36 weeks of gestation and low birth weight babies weighing <2500 gram at birth   can be effectively vaccinated with BCG vaccine in the early neonatal period. However, tuberculin conversion is not a reliable indicator to assess  responses induced by BCG vaccination either 12 weeks or 6 months after vaccination because inspite of negative Mantoux test, the vaccinated infant may still be having an adequate response to BCG vaccine . The local BCG reaction at 8 weeks corresponds to cell mediated immunity conferred by BCG vaccination.

Open Access Article

Evaluation of quadrivalent HPV 6/11/16/18 vaccine efficacy against cervical and anogenital disease in subjects with serological evidence of prior vaccine type HPV infection

Sven-Eric Olsson and 25 others
Pages 696 - 704
http://dx.doi.org/10.4161/hv.5.10.9515
Abstract | PDF

Objective
In the quadrivalent (types 6/11/16/18) HPV vaccine (GARDASIL®/SILGARD®) clinical program, 73% of women aged 16-26 were naïve to all vaccine HPV types. In these women, prophylactic administration of the vaccine was highly effective in preventing HPV 6/11/16/18-related cervical disease. Of the remaining women, 15% of had evidence of past infection with one or more vaccine HPV types (seropositive and DNA negative) at the time of enrollment. Here we present an analysis in this group of women to determine the efficacy of the HPV 6/11/16/18 vaccine against new cervical and external anogenital disease related to the same vaccine HPV type which had previously been cleared. Vaccine tolerability in this previously infected population was also assessed.
Methods
18,174 women were enrolled into 3 clinical studies. The data presented comprise a subset of these subjects (n = 2,617) who were HPV seropositive and DNA negative at enrollment (for ≥1 vaccine type). In each study, subjects were randomized in a 1:1 ratio to receive HPV 6/11/16/18 vaccine or placebo at day 1, month 2 and month 6 (without knowledge of baseline HPV status). Procedures performed for efficacy data evaluation included detailed genital examination, Pap testing, and collection of cervicovaginal and external genital specimens. Analyses of efficacy were carried out in a population stratified by HPV serology and HPV DNA status at enrollment.
Results
Subjects were followed for an average of 40 months. Seven subjects in the placebo group developed cervical disease, and eight subjects developed external genital disease related to a vaccine HPV type they had previously encountered. No subject receiving HPV 6/11/16/18 vaccine developed disease to a vaccine HPV type to which they were seropositive and DNA negative at enrolment.
Conclusions
These results suggest that natural HPV infection-elicited antibodies may not provide complete protection over time, however the immune response to the HPV 6/11/16/18 vaccine appears to prevent reinfection or reactivation of disease with vaccine HPV types. Vaccine-related adverse experiences were higher among subjects receiving vaccine, mostly due to increased injection site adverse experiences.


Open Access Article

Comparison of the immunogenicity and safety of Cervarix™ and Gardasil^® human papillomavirus (HPV) cervical cancer vaccines in healthy women aged 18–45 years

Mark H. Einstein, Mira Baron, Myron J. Levin, Archana Chatterjee, Robert P. Edwards, Fred Zepp, Isabelle Carletti, Francis J. Dessy, Andrew F. Trofa, Anne Schuind and Gary Dubin
Pages 705 - 719
http://dx.doi.org/10.4161/hv.5.10.9518
Abstract | PDF

This observer-blind study compared the prophylactic human papillomavirus (HPV) vaccines, Cervarix™ (GlaxoSmithKline) and Gardasil® (Merck), by assessing immunogenicity and safety through one month after completion of the three-dose vaccination course. Women (n=1106) were stratified by age (18–26, 27–35, 36–45 years) and randomized (1:1) to receive Cervarix™ (Months 0, 1, 6) or Gardasil® (Months 0, 2, 6). At Month 7 after first vaccination, all women in the according-to-protocol cohort who were seronegative/DNA negative before vaccination for the HPV type analyzed had seroconverted for HPV-16 and HPV-18 serum neutralizing antibodies, as measured by pseudovirion-based neutralization assay (PBNA), except for two women aged 27–35 years in the Gardasil® group who did not seroconvert for HPV-18 (98%). Geometric mean titers of serum neutralizing antibodies ranged from 2.3–4.8-fold higher for HPV-16 and 6.8–9.1-fold higher for HPV-18 after vaccination with Cervarix™ compared with Gardasil®, across all age strata. In the total vaccinated cohort (all women who received at least one vaccine dose, regardless of their serological and DNA status prior to vaccination), Cervarix™ induced significantly higher serum neutralizing antibody titers in all age strata (p<0.0001). Positivity rates for anti-HPV-16 and -18 neutralizing antibodies in cervicovaginal secretions and circulating HPV-16 and -18 specific memory B-cell frequencies were also higher after vaccination with Cervarix™ compared with Gardasil®. Both vaccines were generally well tolerated. The incidence of unsolicited adverse events was comparable between vaccinated groups. The incidence of solicited symptoms was generally higher after Cervarix™, injection site reactions being most common. However, compliance rates with the three-dose schedules were similarly high (≥84%) for both vaccines. Although the importance of differences in magnitude of immune response between these vaccines is unknown, they may represent determinants of duration of protection against HPV-16/18. Long-term studies evaluating duration of efficacy after vaccination are needed for both vaccines.