Development and Sustainable Manufacturing of Adjuvanted Pandemic Influenza Vaccines in Developing Countries

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The Biomedical Advanced Research and Development Authority (BARDA), within the Office of the Assistant Secretary for Preparedness and Response (ASPR) in the U.S. Department of Health and Human Services (HHS), provides an integrated, systematic approach to the development and purchase of the necessary vaccines, drugs, therapies, and diagnostic tools for public health medical emergencies. BARDA maintains business collaborations by means of grants, cooperative agreements, and contracts with the public and private sectors, domestically and internationally.Both the H5N1 avian influenza virus and the recent H1N1 swine influenza virus raise the possibility of a massive and deadly influenza pandemic. It is widely accepted that an effective pandemic vaccine could significantly decrease the mortality and morbidity associated with the next pandemic. Unfortunately, the overall global production capacity is insufficient to meet the expected pandemic response needs. Furthermore, developing countries are completely dependent on the availability and accessibility of vaccine manufactured by multinational producers in developed countries. One possible solution to this problem is to increase influenza vaccine production capacity in both developed and developing countries to better address the impact of a pandemic influenza outbreak. The World Health Organization (WHO) and the Program for Appropriate Technologies in Health (PATH) represent important stakeholders in the identification of developing countries with viable vaccine manufacturing capabilities and in providing those institutions with technical guidance and support. In FY 2006-2008, with a total of $24.4 million, BARDA, through a cooperative agreement with World Health Organization (WHO), supported the accelerated development and production of H5N1 influenza human vaccine in Vietnam, Thailand, Indonesia, India, Mexico, Brazil, Egypt, Romania, and Serbia. BARDA funding addresses global and specific country needs for training, laboratory equipment, manufacturing process development, development and validation of product release assay methods, clinical sample analysis, production of pilot lots, scale-up development for vaccine manufacturing, vaccine production equipment, and eventual commercial scale manufacturing of H5N1 vaccines for clinical trials and pandemic usage. To increase pandemic influenza vaccine capacity, an additional approach is to expand the number of doses available by significantly enhancing immunogencity, thereby decreasing the amount of vaccine antigen required in each dose to induce protective immunity (referred to as “antigen sparing”). Another antigen sparing strategy is to enhance immunity such that only one vaccination dose is needed to elicit protective immunity. Potential antigen sparing products may include adjuvants, immunostimulants, immune cytokines, or other biologicals formulated with or co-administered with influenza vaccine antigens. These antigen sparing strategies could potentially extend the pandemic influenza vaccine supply several-fold, substantially improving the ability to rapidly protect local populations in a pandemic and potentially leading to vaccine availability regionally and internationally for countries yet to have domestic production. These are important strategies toward increasing local and regional vaccine supplies and improving real-time response in an influenza pandemic. Strategies that can be implemented by influenza vaccine manufacturers in developing countries unencumbered by intellectual property restrictions and whose platform is not tied to a specific manufacturer or product would be highly advantageous in developing countries. For an antigen sparing strategy to contribute to global pandemic preparedness and response, that technology must be: 1) effective in decreasing the amount of vaccine antigen required to induce a protective immune response; 2) licensed and available at the time of the pandemic; and 3) feasible for implementing a mass vaccination program. Unfortunately, developing countries do not have access to appropriate adjuvant technology in their pandemic influenza development and manufacturing.

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