New Prevention and Treatment Options Against Influenza

Event details
Date | 18.04.2016 |
Hour | 12:15 |
Speaker | Prof. Xavier Saelens, VIB and Ghent University, Ghent (B) |
Location | |
Category | Conferences - Seminars |
BIOENGINEERING SEMINAR
(sandwiches served)
Abstract:
For centuries, influenza viruses have caused acute respiratory disease in human, sometimes with fatal consequences. Vaccines and antivirals are in place to prevent and treat disease caused by human influenza A and B viruses. However, these interventions work suboptimally, mainly as a consequence of the rapid antigenic and genetic evolution of these viruses. We have developed an influenza A vaccine candidate that is based on the conserved extracellular domain of matrix protein (M2e). This domain is naturally poorly immunogenic. However, when fused to a carrier, the M2e antigen can prevent disease following influenza A virus challenge in animal models. We have determined the crystal structure of M2e in complex with the Fab fragment of monoclonal antibodies. This structure revealed that M2e can adopt two different conformations depending on the epitope-specficity of the binding antibodies. This is of interest because M2e-specific IgGs are required for the protection against influenza A virus challenge. We demonstrated that this protection depends on activating F Receptors and alveolar macrophages suggesting that an antibody-dependent phagocytic process operates in vivo to eliminate infected cells. Based on this, we have engineered single chain antibody fragments that can selectively recruit and locally activate T cell to influenza A virus-infected cells. These so-called flu-bi-specific T cell engaging antibody constructs, protect mice against a potentially lethal influenza A virus challenge and represent a novel treatment option against influenza A.
Bio:
PhD: Univ. of Ghent, Ghent, Belgium, 1990
Postdoc: Univ. of Ghent, Ghent, Belgium, 1990-2004
VIB Project Leader since 2005
VIB Expert Scientist since 2009
VIB Group leader as of January 2015
(sandwiches served)
Abstract:
For centuries, influenza viruses have caused acute respiratory disease in human, sometimes with fatal consequences. Vaccines and antivirals are in place to prevent and treat disease caused by human influenza A and B viruses. However, these interventions work suboptimally, mainly as a consequence of the rapid antigenic and genetic evolution of these viruses. We have developed an influenza A vaccine candidate that is based on the conserved extracellular domain of matrix protein (M2e). This domain is naturally poorly immunogenic. However, when fused to a carrier, the M2e antigen can prevent disease following influenza A virus challenge in animal models. We have determined the crystal structure of M2e in complex with the Fab fragment of monoclonal antibodies. This structure revealed that M2e can adopt two different conformations depending on the epitope-specficity of the binding antibodies. This is of interest because M2e-specific IgGs are required for the protection against influenza A virus challenge. We demonstrated that this protection depends on activating F Receptors and alveolar macrophages suggesting that an antibody-dependent phagocytic process operates in vivo to eliminate infected cells. Based on this, we have engineered single chain antibody fragments that can selectively recruit and locally activate T cell to influenza A virus-infected cells. These so-called flu-bi-specific T cell engaging antibody constructs, protect mice against a potentially lethal influenza A virus challenge and represent a novel treatment option against influenza A.
Bio:
PhD: Univ. of Ghent, Ghent, Belgium, 1990
Postdoc: Univ. of Ghent, Ghent, Belgium, 1990-2004
VIB Project Leader since 2005
VIB Expert Scientist since 2009
VIB Group leader as of January 2015
Practical information
- Informed public
- Free