Eliciting Cross-Reactive Antibodies Neutralizing Dengue Virus: A Structural View
Event details
| Date | 15.02.2016 |
| Hour | 12:15 |
| Speaker | Prof. Félix A. Rey, Institut Pasteur, Paris (F) |
| Location | |
| Category | Conferences - Seminars |
DISTINGUISHED LECTURE IN BIOLOGICAL ENGINEERING
(sandwiches served)
Abstract:
Successful vaccines against viral diseases are believed to induce strongly neutralizing antibodies targeting vulnerable sites at the virus surface. A number of viruses have evolved strategies to escape from recognition by neutralizing antibodies, through rapid antigenic drift or by luring the immune system with immunodominant irrelevant epitopes. Novel strategies to identify immunogens presenting viral vulnerability sites to the humoral immune system are therefore necessary.
Dengue disease is caused by four related viruses - called serotype 1 through 4. Recent Phase III vaccine trials have 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 dengue virions, which are partially immature and present uncleaved forms of the viral precursor glycoprotein prM, together with a highly dynamic behavior of the envelope glycoprotein E, leads to numerous antibodies targeting prM and multiple non-functional forms of E, which are non-neutralizing.
We have identified the epitope of a category of human antibodies potently 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 morphogenesis. Based on our results, we propose the development of immunogens carrying stabilized forms of the E dimer such that the characterized new epitope is exposed on a re-surfaced molecule, focusing the immune system on this particularly vulnerable site.
Within this context, in the seminar I will 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:
Prof. Félix Rey, a leading figure in the area of emergent viral pathogens, is Director of the Unit of structural virology at the Institut Pasteur. Originally from Argentina and a trained physicist, Dr. Rey has done postdoctoral 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 current position at the Institut Pasteur in 2004.
(sandwiches served)
Abstract:
Successful vaccines against viral diseases are believed to induce strongly neutralizing antibodies targeting vulnerable sites at the virus surface. A number of viruses have evolved strategies to escape from recognition by neutralizing antibodies, through rapid antigenic drift or by luring the immune system with immunodominant irrelevant epitopes. Novel strategies to identify immunogens presenting viral vulnerability sites to the humoral immune system are therefore necessary.
Dengue disease is caused by four related viruses - called serotype 1 through 4. Recent Phase III vaccine trials have 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 dengue virions, which are partially immature and present uncleaved forms of the viral precursor glycoprotein prM, together with a highly dynamic behavior of the envelope glycoprotein E, leads to numerous antibodies targeting prM and multiple non-functional forms of E, which are non-neutralizing.
We have identified the epitope of a category of human antibodies potently 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 morphogenesis. Based on our results, we propose the development of immunogens carrying stabilized forms of the E dimer such that the characterized new epitope is exposed on a re-surfaced molecule, focusing the immune system on this particularly vulnerable site.
Within this context, in the seminar I will 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:
Prof. Félix Rey, a leading figure in the area of emergent viral pathogens, is Director of the Unit of structural virology at the Institut Pasteur. Originally from Argentina and a trained physicist, Dr. Rey has done postdoctoral 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 current position at the Institut Pasteur in 2004.
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