SEP 08, 2020 9:00 AM PDT

Keynote Presentation: A Universal Influenza Virus Vaccine

C.E. Credits: P.A.C.E. CE Florida CE
Speaker
  • Professor and Chair Department of Microbiology, Professor in Department of Medicine and Infectious Diseases, Icahn School of Medicine at Mount Sinai
    Biography

      Peter Palese is a Professor of Microbiology and the Chair of the Department of Microbiology at the Icahn School of Medicine at Mount Sinai.  His research is in the area of RNA-containing viruses with a special emphasis on influenza viruses. Specifically, 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 the study of the structure/function relationships of viral genes, for investigation of viral pathogenicity and for development and manufacture of novel vaccines.  An improvement of this technique has been effectively used by him and his colleagues to reconstruct and study the pathogenicity of the highly virulent, but extinct, 1918 pandemic influenza virus.  Work in collaboration with Dr. Adolfo Garcia-Sastre 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.   In recent years most of the efforts by Dr. Palese and by his collaborators at Mount Sinai, Dr. Adolfo Garcia-Sastre and Dr. Florian Krammer, have been directed at developing a Universal Influenza Virus Vaccine. Since the beginning of the year there has been a shift in directions as work on COVID-19 has become central to the efforts by Dr. Palese. Dr. Palese is a Member of the National Academy of Sciences, a Member of the National Academy of Medicine, a Fellow of the American Academy of Arts and Sciences, and a Fellow of the National Academy of Inventors


    Abstract

    Seasonal and pandemic influenza virus infections can cause significant disease worldwide. Current vaccines only provide limited, short-lived protection, and antigenic drift/shift in the hemagglutinin (HA) surface glycoprotein necessitates their annual reformulation and re-administration. To overcome these limitations, universal influenza virus vaccine strategies aim at eliciting broadly protective antibodies to conserved epitopes of the HA. We have developed ‘chimeric’ HA constructs which retain the conserved stalk domain of the HA and have exotic HA heads. Vaccination and boosting with such constructs successfully redirects the immune system in animals and in humans towards the conserved immune sub-dominant domains of the HA stalks resulting in an antigenic silencing of the HA heads and a protective immune response facilitated by the conserved HA stalks. In mice and ferrets such a strategy protects the animals against challenge with different influenza A strains as well as against different influenza B variants. Although phase I trials have been successfully conducted, further extensive trials will be necessary in the future in order to make this ‘chimeric’ HA approach an FDA-approved vaccine.

    Learning Objectives:

    1. Why is antigenic drift/shift responsible for the occasional very low efficacy of influenza virus vaccines and why is the composition of influenza virus vaccines adjusted on an annual basis?

    2. Why are other vaccines not altered on an annual basis and why can they be used effectively over many decades? What is the principle behind the approach to develop a universal influenza virus vaccine?

    3. Why is the technology of reverse genetics instrumental in making safe and protective universal influenza virus vaccines?


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