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

2. NIAID Research Pathway

3. 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.

4. 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.

5. 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)

6. 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).

7. 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).

8. NIAID-supported research for the development of new influenza vaccines
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

9. 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; H7N7; 2004 H5N1 currently being developed)