Influenza Vaccine Development

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Influenza Vaccine Development

• Cristina Cassetti, Ph.D.
• Influenza Program Officer
• Division of Microbiology and Infectious Diseases
• NIAID

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NIAID Research Pathway
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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.

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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.

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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)

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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).

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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).

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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

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NIAIDs 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)