Low Vaccination Rates Force Governments to Cancel H1N1 Flu Vaccine Orders

Just a few month ago a forecast made by analysts of Market Research Media Ltd seemed to undermine impact of the H1N1 pandemic on the vaccine market - according to this market research report “Global Pandemic Influenza Preparedness Market Forecast 2010-2015” the worldwide government spending on Pandemic Influenza Preparedness would grow at rather moderate rate of a 5% CAGR. At the height of H1N1 pandemic and CDC announcements about vaccine shortages the market demand seemed insatiable. Yet reality creeps in. Vaccination rates are low even among healthcare workers, governments are cutting swine flu vaccine orders by 30% - 50%.The most frequent reasons given for passivity of population in getting vaccinated are low estimation of the risk of infection, fear of adverse effects, and scepticism whether the vaccine offered adequate protection.

Governments are caught in the conflict between encouraging pharmaceutical companies to make flu vaccine and wasting limited funds on doses that are never given. Unless H1N1 would come back in a next wave, the moderate flu preparedness market forecast will hold true.

Influenza Vaccine Adjuvant to Improve Effectiveness of Flu Vaccine for Elders

Juvaris BioTherapeutics, Inc., a biotech company developing adjuvanted vaccines for infectious diseases, has begun enrolling patients in a Phase 2 clinical trial of JVRS-100, an adjuvant for seasonal influenza vaccines in the elderly population. Seasonal influenza affects approximately one billion people worldwide each year resulting in 5 million severe illnesses and 500,000 deaths. Approximately 90 percent of the deaths occur in the elderly. Seasonal influenza vaccines, which are widely used in the U.S. and developed countries, are generally effective in children and young adults, but are effective in only 30 percent of the elderly population. Manufacturers of influenza vaccines are actively pursuing adjuvanted vaccines in order to improve efficacy and reduce vaccine dosage requirements.

“There is a significant need to improve the efficacy of seasonal influenza vaccines for elderly individuals given that current vaccines are effective in only 30 percent of this population. Results from our first clinical trial demonstrated that JVRS-100 enhances both antibody and T-cell mediated immune responses and, thus, holds potential for the development of improved influenza protection, especially in a population more susceptible to complications from influenza infection,” said Tom Monath, MD, acting Chief Medical Officer of Juvaris.

“Developing an adjuvanted influenza vaccine that confers superior immunity leading to better protection from disease is a critical need and this Phase 2 trial in the elderly will yield proof-of-concept for JVRS-100 in a patient population with significant unmet needs. We look forward to advancing this trial toward its completion in the first half of 2010,” said Grant Pickering, President and Chief Executive Officer of Juvaris.

The randomized, double-blind, controlled trial will enroll approximately 472 subjects 65 years and older and compare antibody and T-cell responses to trivalent inactivated influenza vaccine administered with and without the JVRS-100 adjuvant. Primary objectives of the study are to assess its safety, tolerability and ability to enhance immune responses (both antibody and cellular immunity) to the influenza vaccine. The study is also intended to define the most effective dose of the JVRS-100 adjuvant and will test three different doses.

JVRS-100
JVRS-100 is a cationic lipid-DNA complex that is being developed as an adjuvant to improve the effectiveness of existing vaccines and to develop new vaccines against a variety of infectious diseases. Research indicates that the mechanism of action of JVRS-100 is distinct from other known adjuvants. The adjuvant complex self-assembles with disease-specific antigens and induces substantial antibody- and cell-mediated immune responses, particularly induction of CD4+ and CD8+ T lymphocytes. Immunological responses elicited by the lipid-DNA complexes have been successfully demonstrated in both prophylactic and therapeutic vaccine settings in multiple species. This platform provides the opportunity to develop many disease-specific immunotherapy products for which there are significant unmet medical needs.

New Joint Venture To Build Asia’s Largest Influenza Vaccine Facility

Microbix, (TSX:MBX) a Canadian developer of a patented technology that increases influenza vaccine yields, has signed a joint venture agreement with the Hunan Biopharmaceutical Co. Ltd. (a Chinese Hunan Province state-owned enterprise) for initial financing to build Asia’s largest influenza vaccine production facility and the third largest vaccine plant in the world. A newly formed joint venture will build and operate a $200-million facility, located in Changsha National Biomedical Park near Changsha City, the capital of Hunan Province. Production facility will have the capacity to produce more than 100 million doses of seasonal influenza vaccine annually, and up to 300 million doses of a pandemic influenza vaccine in the event of an outbreak to immunize against a single strain of influenza.

The facility, for which construction will begin in early 2010 and be fully operational by 2013, will be designed around Microbix VIRUSMAX(TM) vaccine technology. More than five years in development at Microbix, VIRUSMAX is designed to increase influenza vaccine yields and has demonstrated an average yield increase of two-fold over current production methods.

“We’re pleased that our innovative VIRUSMAX influenza vaccine technology will contribute significantly to seasonal and pandemic influenza preparedness in the future. This facility will make China an important source of influenza vaccine in the Asia region as well as offering significant capacity for the Chinese market which is growing significantly. In five years, the China market is expected to demand up to 500 million influenza vaccine doses annually,” said William J. Gastle, Microbix Chairman and CEO.

Currently only two percent of the China population is immunized against flu, while the World Health Organization recommends that countries have the capacity to vaccinate at least 60 percent of their populations. As the project progresses, Hunan will provide additional funding through debt and has guaranteed the purchase of 100 million influenza vaccine doses. On all vaccine produced at the facility, Microbix will receive royalty payments and hold exclusive marketing rights outside of China.

Later on the Microbix-Hunan facility will seek approval by the U.S. Food and Drug Administration and European Medicines Agency for its influenza vaccines.

DNA Vaccine Potential

Inovio has created a novel platform for developing and delivering “universal” DNA-based vaccines against diseases such as influenza, HIV, malaria, dengue, and cervical cancer. Inovio’s universal vaccines have shown preclinical results indicating their potential to protect against new, unknown strains of an infectious disease such as the currently circulating H1N1 “swine flu.”

Dr. J. Joseph Kim, president and CEO of Inovio Biomedical Corporation, presented DNA vaccine potential at the World Knowledge Forum in Seoul, South Korea. In Dr. Kim’s presentation “Developing universal SynCon™ vaccines to improve human lives” he introduced Inovio’s proprietary DNA vaccine development platform, an approach to producing DNA-based vaccines with great potential to prevent and treat chronic infectious diseases and cancer.

Dr. Kim highlighted recent results from a combination of its synthetic consensus (SynConTM) H1N1 influenza vaccine candidates, which achieved protective antibody responses against the novel pandemic influenza A/H1N1 (2009) in 100% of tested ferrets. The ferret model is widely considered to be the most representative of human influenza; achieving in ferrets a level of antibody titers correlated with protection in humans is a critical milestone in influenza vaccine development. In this experiment, a single vaccination showed induction of positive immune responses in 78% (7 of 9) of ferrets, with a mean HI titer of 1:42 (a titer is a measure of antibody levels against a virus; in the case of influenza, an HI titer exceeding 1:40 in animals, including humans, is considered to be a protective level). After two booster shots, 100% of immunized ferrets had HI titers greater than 1:40, with the mean titer rising to 1:390, representing a very strong increase in antibodies.

Inovio has now completed cGMP clinical product manufacturing of its H1N1 SynCon™ vaccine candidate, an important step in advancing the candidate toward clinical testing. As part of the company’s strategy for its universal influenza vaccine, the H1N1 vaccine would be combined with Inovio’s H5N1 vaccine candidate, for which an IND has already been submitted to the FDA. On the path toward its universal influenza vaccine concept, Inovio will also mix in constructs for H2N2 and H3N2 influenza sub-types; together these four sub-types were responsible for most of the seasonal and pandemic influenza outbreaks of the last 100 years.

Dr. Kim also described the company’s recently reported results for its therapeutic HPV/cervical cancer DNA vaccine. Inovio reported significant T-cell responses in 50% (3 of 6) and strong antibody responses in 83% (5 of 6) subjects treated with just the first, low-dose group in its phase I clinical study. Generating a significant T-cell immune response is considered imperative to treating cancers and infectious diseases such as HIV and hepatitis C virus. The T-cell immune responses generated in this study were among the strongest generated by a DNA vaccine in humans.

U.S. Government Funds Vaccine Adjuvant Development

U.S. government, through the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, has awarded six new research contracts to discover and characterize novel adjuvants, substances that can be added to vaccines to enhance the protective immune response they induce.

Currently, the only vaccine adjuvant approved for use in the United States is an aluminum mixture known as alum.

NIAID has awarded a total of approximately $60 million over five years for these contracts. The awardees will identify novel compounds with the potential to be vaccine adjuvants. All compounds will be tested in animal models and human cells to determine how well they stimulate the immune response. The investigators also will examine and describe the cellular reactions the compounds induce.

The awardees of the adjuvant contracts are

• James R. Baker, Jr., M.D., University of Michigan, Ann Arbor
• Dennis A. Carson, M.D., Moores Cancer Center, University of California San Diego, La Jolla
• Sunil A. David, M.D., Ph.D., University of Kansas, Lawrence
• Michael J. Gale, Jr., Ph.D., University of Washington School of Medicine, Seattle
• David A. Johnson, Ph.D., Corixa Corporation (now part of GlaxoSmithKline Biologicals), Hamilton, Mont.
• Peter Palese, Ph.D., Mount Sinai School of Medicine, New York City

“The goal of these awards is to find safe new adjuvants that will boost the effectiveness of vaccines. Adjuvants can be used not only to enhance the immune response to a vaccine and thereby offer better protection but also to extend the vaccine supply if needed, enabling more people to be vaccinated with fewer doses” says NIAID Director Anthony S. Fauci, M.D.

“The goal of these awards is not only to identify new adjuvant candidates but also to describe how these candidates work. We would hope that these adjuvant candidates will become part of a robust pipeline leading to the development of many different vaccines” says Helen Quill, Ph.D., chief of NIAID’s basic immunology research branch.

“A first round of NIAID contracts, awarded in 2003, limited the discovery of novel adjuvants to those that stimulated the only group of innate immune receptors known at the time. With this second round of awards, we intend to increase the number of adjuvant candidates by expanding the research scope to include all known innate immune receptors” says Daniel Rotrosen, M.D., director of NIAID’s Division of Allergy, Immunology, and Transplantation.

The awardees of the adjuvant contracts will work to identify and characterize novel adjuvants that trigger receptors of the inborn, or innate, immune system. These receptors recognize and bind small molecules that are unique to harmful microorganisms. Binding stimulates an immediate innate immune response, a broadly protective reaction. The innate immune response also is required for the development of the highly specific antibody and T-cell responses that characterize long-term immunity.

The investigators also will seek to identify the cellular receptor for each of the novel adjuvant candidates, determine how it triggers the innate immune response, and then make changes to the adjuvant to improve its ability to induce the innate immune response. Although a number of innate immune receptors already have been described, many more likely exist and are expected to be uncovered in the course of these projects.

Vaccines Conference in Boston, September 23 - 25, 2009

The Vaccines Development Conference brings together scientists and industry experts in all aspects of vaccine development to share what’s working and not working for them, and to address your key vaccine development challenges and questions. The conference is held Boston, September 23 - 25, 2009.

Conference highlights:

• Novel Adjuvant Development: Hear current advances in novel adjuvants with discussions and case studies from National Cancer Institute, NIH, Big DNA, Datamonitor and Vical
• Thermostability: Learn formulation strategies from Program for Appropriate Technology in Health
• Delivery: Uncover the latest vaccine delivery advances and the stabilization, potency testing, and formulation developments associated with needle-free delivery with case studies from Georgia Tech, Aktiv-Dry/University of Colorado, and Program for Appropriate Technology in Health (PATH)
• Analytical Testing: Master the most appropriate and efficient analytical testing methods and techniques to evaluate and analyze your vaccines with case studies from Wyeth Vaccines and Genzyme
• Potency and Immunogenicity Testing: Strategize with Acambis/Sanofi-Pasteur, VirXsys, and BigDNA to uncover strategies for improved vaccine assessment
• Manufacturing & Process Development: Tap into efficient and comparable manufacturing, scale up, and tech transfer approaches from Immunovaccine Technologies, BigDNA, and NIH.

Cancer Vaccine: Vical Presents Positive Preclinical Results

Vical Incorporated presents encouraging results from animal studies of a peptide-based cancer vaccine formulated with the company’s Vaxfectin(R) adjuvant. Sean M. Sullivan, Ph.D., Vical’s Executive Director of Pharmaceutical Sciences, is presenting data at the IIRUSA Vaccines Development Forum (Boston - September 23-25) demonstrating the adjuvant’s ability to enhance immune responses of cancer antigen-based vaccines in addition to a broad variety of DNA- and protein-based vaccines against infectious diseases.

“The Vaxfectin(R) adjuvant continues to demonstrate tremendous versatility in both infectious disease and cancer applications,” said Alain P. Rolland, Pharm.D., Ph.D., Vical’s Executive Vice President of Product Development. “The latest data showed that mice vaccinated with a Vaxfectin(R)-formulated TRP-2 melanoma tumor antigen peptide achieved significant improvements in cellular immune responses, reduced numbers of tumors, and a survival advantage compared with mice receiving control or no treatment. These data encourage further development of additional cancer applications and exploration of partnering opportunities.”

Results from a mouse study demonstrated an 88-fold increase in antigen-specific CD8+ T-cell responses at low doses and a 45-fold increase at high doses with a Vaxfectin(R)-formulated peptide-based cancer vaccine compared with unformulated vaccine. The Vaxfectin(R)-formulated cancer peptide also resulted in 7- to 14-fold higher responses than obtained with TRP-2 formulated with Freund’s adjuvant. In addition, the Vaxfectin(R)-formulated vaccine demonstrated a clear dose response when used at a constant adjuvant-to-peptide ratio. When evaluated against induced melanoma tumors, mice treated with the vaccine had statistically significantly fewer tumor lesions in the lungs compared with mice receiving no treatment or receiving a Vaxfectin(R)-formulated peptide control treatment. The mice receiving Vaxfectin(R)-formulated vaccine also demonstrated a significant survival advantage compared with untreated mice.

Vaxfectin(R)-formulated vaccines have demonstrated good tolerability and significant immune responses in multiple animal models, including nonhuman primates, and underwent successful initial human testing with the company’s H5N1 pandemic influenza DNA vaccines. Vaxfectin(R) has also demonstrated a dose-sparing effect (the ability to achieve the same vaccine effectiveness with lower vaccine doses) with commercial seasonal influenza and government-stockpiled protein-based H5N1 pandemic influenza vaccines.

HIV Vaccine: GenVec Receives Federal Funding

GenVec will receive up to $2.3 million for the 4th year to support the generation of HIV vaccine candidates with GenVec’s alternate adenovirus serotype technology. The National Institute of Allergy and Infectious Disease (NIAID) has executed its third option period (year four) under a previously announced, five-year contract with GenVec valued at up to $52 million for the production of HIV vaccines.

World Vaccine Congress Lyon 2009

World Vaccine Congress Lyon 2009, a Europe’s leading vaccine conference, will be held on October 5-8, 2009 in Lyon, France. The World Vaccine Congress Lyon is the annual vaccine conference addressing every aspect of vaccine research, vaccine development and vaccine manufacturing.

• Representation from key European Commission and regulatory agencies
• DG Research, DG SANCO, ECDC, EDQM, CHMP, VWP, MHRA, PEI, FAMHP and MEB provide vision and clarity on future industry progress and opportunities
• Europe’s largest commercial vaccine industry congress for decision makers across European and North America regions
• Including World class multiple speaker representation from Baxter, GSK Biologicals, MedImmune, Novartis Vaccines and Diagnostics, Pfizer, sanofi pasteur, sanofi Pasteur MSD, Solvay and Wyeth Vaccines
• Critical market opportunities outlined in billion Euro vaccine market
  European policy frameworks, vaccine regulation and authorisation, vaccine R&D innovation and introduction, Influenza market sustainability, corporate growth strategies and funding sources

It’s Europe’s premier vaccine event, with over 70 speakers from top pharmaceuticals & biotechs worldwide and representation from key European Commission and regulatory agencies!

Top Speakers:
Dr. Olesen - European Commision
Dr.Lopalco - ECDC
Didier Hoch - President Sanofi Pasteur MSD
Dr. Southerton - Executive Director Pfizer

To see the agenda: Download congress agenda

Broad U.S. Patent Issued for Vaxfectin(R)-Formulated DNA Vaccines for Influenza

Vical Incorporated receives U.S. Patent No. 7,582,613 covering Vaxfectin(R)-formulated DNA vaccines for influenza. The patent provides broad coverage for any circulating or potential influenza viruses, including both seasonal and pandemic strains.

The company is currently developing Vaxfectin(R)-formulated DNA vaccines for both H5N1 avian-origin and H1N1 swine-origin pandemic influenza. Both vaccines are formulated with the company’s Vaxfectin(R) adjuvant, a novel lipid-based formulation which has demonstrated significant immune-enhancing ability with a broad range of DNA vaccines and up to 30-fold immune-enhancing ability with a conventional seasonal influenza vaccine. Vaxfectin(R)-formulated H5N1 influenza DNA vaccines completed Phase 1 human testing in 2008.

DNA vaccines encode certain proteins associated with a target pathogen, rather than using any part of the pathogen itself, and can prime the immune system as well as induce potent antibody and T-cell immune responses. DNA vaccines contain no viral particles, are non-infectious, and can be administered on a repeat basis without unwanted immune responses. Additionally, DNA vaccines have the potential to achieve proof of concept more quickly and cost-effectively than conventional vaccines, and can be manufactured using uniform methods of fermentation and purification, allowing significantly faster development and production.

The new patent broadly covers DNA vaccines formulated with any cationic lipid/co-lipid adjuvant formulations from the class including Vaxfectin(R), and targeting any strain of influenza. It adds to Vical’s family of patents in the United States and other key regions based on the company’s discovery that administering genetic sequences such as DNA or RNA into the body, without the use of viral delivery vehicles, may cause expression of the proteins encoded by the genetic sequences. Vical has additional issued patents covering the composition and use of the Vaxfectin(R) adjuvant.