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)

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)