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Toward a universal influenza virus vaccine

Wednesday, April 30, 2014

Speaker

Peter Palese, Ph.D.
Professor and Chair, Department of Microbiology
Mount Sinai School of Medicine

Dr. Palese’s research is in the area of RNA-containing viruses with a special emphasis on influenza viruses. He established the first genetic maps for influenza A, B, and C viruses, identified the function of several viral genes, and defined the mechanism of neuraminidase inhibitors (which are now FDA-approved antivirals). He was also a pioneer in the field of reverse genetics for negative-strand RNA viruses, which allows the introduction of site-specific mutations into the genomes of these viruses. This technique is crucial for studying the structure and function relationships of viral genes, investigating viral pathogenicity, and for developing and manufacturing novel vaccines. In addition, Dr. Palese and his colleagues have effectively used an improved technique to reconstruct and study the pathogenicity of the highly virulent, but extinct, 1918 pandemic influenza virus. His recent work in collaboration with Dr. Adolfo Garcia-Sastre (Mount Sinai) has revealed that most negative-strand RNA viruses possess proteins with interferon antagonist activity, enabling them to counteract the antiviral response of the infected host.

Summary

Because influenza viruses are constantly changing, it’s difficult to develop effective vaccines against them. Two molecules on the surface of the virus control its infectivity: hemagglutinin and neuraminidase. Current influenza virus vaccines predominantly elicit a protective immune response to the immunodominant but variable head of the hemagglutinin. This approach is effective, especially when the vaccine strain closely matches the circulating virus. Another vaccine strategy involves redirecting the response to the more conserved stalk domain of the hemagglutinin and the immunosubdominant neuraminidase. This can be achieved by using vaccine strains that express chimeric hemagglutinin proteins whereby the head of the hemagglutinin represents an exotic subtype never encountered by humans under natural conditions. Such influenza virus constructs are likely to boost memory B-cells directed against conserved epitopes of the hemagglutinin stalk and the neuraminidase, and thus should afford broad spectrum protection against a variety of antigenic drift and shift strains.


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