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SUMMARY:Eliciting Cross-Reactive Antibodies Neutralizing Dengue Virus: A S
 tructural View
DTSTART:20160215T121500
DTSTAMP:20260510T135201Z
UID:a83ffb6ad00e4ae42a47da4bf5d642edc4b52f1c508daee2073327ab
CATEGORIES:Conferences - Seminars
DESCRIPTION:Prof. Félix A. Rey\, Institut Pasteur\, Paris (F)\nDISTINGUIS
 HED LECTURE IN BIOLOGICAL ENGINEERING(sandwiches served)Abstract:\nSuccess
 ful vaccines against viral diseases are believed to induce strongly neutra
 lizing antibodies targeting vulnerable sites at the virus surface. A numbe
 r of viruses have evolved strategies to escape from recognition by neutral
 izing antibodies\, through rapid antigenic drift or by luring the immune s
 ystem with immunodominant irrelevant epitopes.  Novel strategies to ident
 ify immunogens presenting viral vulnerability sites to the humoral immune 
 system are therefore necessary.\nDengue disease is caused by four related 
 viruses - called serotype 1 through 4. Recent Phase III vaccine trials hav
 e shown incomplete protection.  Simultaneous protection against all four 
 serotypes is important because of an antibody-dependent enhancement (ADE) 
 effect may lead to more severe disease in patients having non-neutralizing
  antibodies against the infecting serotype.  The high heterogeneity of de
 ngue virions\, which are partially immature and present uncleaved forms of
  the viral precursor glycoprotein prM\, together with a highly dynamic beh
 avior of the envelope glycoprotein E\, leads to numerous antibodies target
 ing prM and multiple non-functional forms of E\, which are non-neutralizin
 g.\nWe have identified the epitope of a category of human antibodies poten
 tly neutralizing all four dengue virus serotypes to be a conserved site at
  the interface between the two subunits of the functional but metastable E
  dimer. The identified epitope is conserved across serotypes because it is
  also involved in specific interactions with prM during particle morphogen
 esis. Based on our results\, we propose the development of immunogens carr
 ying stabilized forms of the E dimer such that the characterized new epito
 pe is exposed on a re-surfaced molecule\, focusing the immune system on th
 is particularly vulnerable site.\nWithin this context\, in the seminar I w
 ill give an overview of the flavivirus architecture\, the conservation of 
 the vulnerability site across flaviviruses\, and the prospects for vaccine
  against other pathogenic flaviviruses\, such as zika virus.Bio:\nProf. F
 élix Rey\, a leading figure in the area of emergent viral pathogens\, is 
 Director of the Unit of structural virology at the Institut Pasteur. Origi
 nally from Argentina and a trained physicist\, Dr. Rey has done postdoctor
 al research in biochemistry at Harvard University before joining the CNRS 
 in France\, where he has been for most of his career. He has taken his cur
 rent position at the Institut Pasteur in 2004.
LOCATION:SV1717.1 http://map.epfl.ch/?room=sv1717.1
STATUS:CONFIRMED
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