UNDERSTANDING THE MECHANISM OF YELLOW FEVER 17D VACCINE EFFICACY: AN IMMUNO-STRUCTURAL APPROACH TOWARDS THE DESIGN OF A PAN-FLAVIVIRUS VACCINE

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Yellow fever virus re-emergence in Africa in a globalized economy presents a significant risk of spillover to unaffected areas in Asia. Despite the availability of the YF17D vaccine, its low supply and our poor insight into viral biology and vaccine immunogenicity bear the risk to be unprepared for an exponential spread of infection. Using a structural approach focused on the viral envelope protein, we recently discovered important differences in the host-virus interaction between YF wild type and vaccine strains. Our bi-national consortium proposes a multi-disciplinary approach based on diverse expertise to assess: 1) viral entry and antigen presentation in relevant cells, 2) the differential cellular response to vaccine and wild type strains, and 3) the B-cell receptor and antibody repertoire in both vaccinated humans and wild type-infected or vaccinated primates. Understanding the mechanism of YF17D immunogenicity will allow designing new approaches towards a pan-flavivirus vaccine.