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Scientists identify lab-made proteins that neutralize multiple strains of seasonal and pandemic flu
Date:2/22/2009

membrane fusion and virus entry into the cell.

When they surveyed more than 6,000 available HA genetic sequences of the 16 HA subtypes, they found the pockets to be very similar within each Group but to be significantly different between the two Groups. The genetically stable pockets, they note, may be a result of evolutionary constraints that enable virus-cell fusion. This could also explain why they did not detect so-called escape mutants, viruses that elude the monoclonal antibodies through genetic mutation.

"One of the most remarkable findings of our work is that we identified a highly conserved region in the neck of the influenza hemagglutinin protein to which humans rarely make antibodies," says Dr. Marasco. "We believe this is because the head of the hemagglutinin protein acts as a decoy by constantly undergoing mutation and thereby attracting the immune system to produce antibodies against it rather than against the pocket in the neck of the protein."

Their findings could also assist vaccine developers. Current influenza vaccines target the constantly mutating head of the HA protein and do not readily generate antibodies against the conserved region in the neck.

"An important goal is to redirect the immune response of vaccines to this invariable region of the hemagglutinin to try to obtain durable lifelong immunity," Dr. Marasco states.

The monoclonal antibodies identified in their paper are very well-characterized, Dr. Marasco notes, and he is optimistic about their further clinical development. "These are fully human monoclonal antibodies that are ready for advanced preclinical testing," he says. He currently is arranging to use NIAID research resources to take the next steps: first, testing the antibodies in ferrets, the gold standard animal model for influenza, and then developing a clinical grade version of one antibody that could enter human clinical trials as soon as 18 months from when the development
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Contact: Laurie K. Doepel
doepel@nih.gov
301-402-1663
NIH/National Institute of Allergy and Infectious Diseases
Source:Eurekalert

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