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Influenza Vaccine Development. Cristina Cassetti, Ph.D. Influenza Program Officer Division of Microbiology and Infectious Diseases NIAID. NIAID Research Pathway. Vaccines currently available. Trivalent inactivated vaccine (TIV) Live attenuated vaccine (LAIV)
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Influenza Vaccine Development Cristina Cassetti, Ph.D. Influenza Program Officer Division of Microbiology and Infectious Diseases NIAID
Vaccines currently available • Trivalent inactivated vaccine (TIV) • Live attenuated vaccine (LAIV) Both vaccines target primarily the anti-HA antibody response and are made by: • generating a high growth reference virus (classical reassortment). • growing the vaccine in embryonated chicken eggs.
Advantages of current influenza vaccines • TIV first licenced in US in 1945. • 70-90% efficacy in healthy adults (in preventing influenza) • Dramatically reduce complications from influenza, including hospitalization and death. • Can reduce the risk for outbreaks by inducing herd immunity.
Limitation of current vaccines • A new vaccine has to be generated every year . • The vaccine strains for the upcoming influenza season have to be predicted at least 6 months in advance. • Classical reassortment technology is cumbersome and sometimes does not lead to the ideal reference virus. • Classical reassortment requires availability of an acceptable clinical isolate. • Vaccine manufacturing relies on the availability of hundreds of millions of embryonated chicken eggs. • TIV has limited efficacy in the elderly (30% to 40% efficacy in preventing influenza)
NIAID-supported research for the development of new influenza vaccines I • Strategies to develop vaccines that have enhanced immunogenicity or are broadly-protective: • Improve TIV with adjuvants, mucosal delivery or increased dose. • New vaccines that target conserved proteins (NP and M2) • Ongoing clinical studies to elucidate the immune responses to LAIV compared to TIV and natural infection (Arvin, CA).
NIAID-supported research for the development of new influenza vaccines II • Establishment of reverse genetics technology in ’99. • Potentially faster and easier to generate of vaccine reference strains (currently being used to make Vietnam H5N1 reference viruses). • Eliminates the need for working directly with the clinical isolate. • Can engineer HA of pandemic virus strains without the basic amino acids at the cleavage site (associated with high virulence).
NIAID-supported research for the development of new influenza vaccines. III New technologies for the rapid production of influenza vaccines: • Tissue culture-based system (as alternative to eggs) • DNA-based vaccines • Recombinant baculovirus-expressed protein vaccines New methods for vaccine delivery: • Skin patch • Gene gun
NIAID’s commitment to further develop influenza vaccines • Biodefence research opportunities • Challenge grants • Small Business biodefence program • Contracts: • Pre-clinical development (VRPRU) • DMID supported clinical trial network (VTEUs) • Repository for influenza reagents • Pandemic preparedness in Asia: Reference strain library (2003 H5N1; 2003 H7N7; 2004 H5N1 currently being developed)