- home
- Advanced Search
Filters
Clear All- COVID-19
- Swiss National Science Foundation
- BROADimmune
- CH
- English
- COVID-19
- Swiss National Science Foundation
- BROADimmune
- CH
- English
Loading
description Publicationkeyboard_double_arrow_right Article 2016Embargo end date: 28 Jul 2016 Switzerland EnglishPublisher:ETH Zurich Funded by:EC | INFLUENZA FUSION, SNSF | Analytic vaccinology, EC | BROADimmuneEC| INFLUENZA FUSION ,SNSF| Analytic vaccinology ,EC| BROADimmuneNicole L. Kallewaard; Davide Corti; Patrick J. Collins; Ursula Neu; Josephine M. McAuliffe; Ebony Benjamin; Leslie Wachter-Rosati; Frances J. Palmer-Hill; Andy Q. Yuan; Philip A. Walker; Matthias K. Vorlaender; Siro Bianchi; Barbara Guarino; Anna De Marco; Fabrizia Vanzetta; Gloria Agatic; Mathilde Foglierini; Debora Pinna; Blanca Fernandez-Rodriguez; Alexander Fruehwirth; Chiara Silacci; Roksana W. Ogrodowicz; Stephen R. Martin; Federica Sallusto; JoAnn Suzich; Antonio Lanzavecchia; Qing Zhu; Steven J. Gamblin; John J. Skehel;pmc: PMC4967455
handle: 20.500.11850/118907
Summary Influenza virus remains a threat because of its ability to evade vaccine-induced immune responses due to antigenic drift. Here, we describe the isolation, evolution, and structure of a broad-spectrum human monoclonal antibody (mAb), MEDI8852, effectively reacting with all influenza A hemagglutinin (HA) subtypes. MEDI8852 uses the heavy-chain VH6-1 gene and has higher potency and breadth when compared to other anti-stem antibodies. MEDI8852 is effective in mice and ferrets with a therapeutic window superior to that of oseltamivir. Crystallographic analysis of Fab alone or in complex with H5 or H7 HA proteins reveals that MEDI8852 binds through a coordinated movement of CDRs to a highly conserved epitope encompassing a hydrophobic groove in the fusion domain and a large portion of the fusion peptide, distinguishing it from other structurally characterized cross-reactive antibodies. The unprecedented breadth and potency of neutralization by MEDI8852 support its development as immunotherapy for influenza virus-infected humans. Highlights • Binding to all influenza A subtypes neutralizing seasonal and pandemic strains • Utilizes a rare VH (VH6-1) and carries a low level of somatic mutations • Highly conserved epitope encompassing fusion peptide and hydrophobic groove • Superior therapeutic window compared to oseltamivir in animals Identification of a human monoclonal antibody that reacts effectively with all influenza A hemagglutinin subtypes paves the way for developing immunotherapy for people infected with the flu virus. Graphical Abstract
Cell arrow_drop_down CellArticle . 2016Full-Text: http://europepmc.org/articles/PMC4967455Data sources: PubMed Centraladd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.3929/ethz-b-000118907&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.euAccess RoutesGreen hybrid 318 citations 318 popularity Top 1% influence Top 10% impulse Top 0.1% Powered by BIP!more_vert Cell arrow_drop_down CellArticle . 2016Full-Text: http://europepmc.org/articles/PMC4967455Data sources: PubMed Centraladd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.3929/ethz-b-000118907&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eu
Loading
description Publicationkeyboard_double_arrow_right Article 2016Embargo end date: 28 Jul 2016 Switzerland EnglishPublisher:ETH Zurich Funded by:EC | INFLUENZA FUSION, SNSF | Analytic vaccinology, EC | BROADimmuneEC| INFLUENZA FUSION ,SNSF| Analytic vaccinology ,EC| BROADimmuneNicole L. Kallewaard; Davide Corti; Patrick J. Collins; Ursula Neu; Josephine M. McAuliffe; Ebony Benjamin; Leslie Wachter-Rosati; Frances J. Palmer-Hill; Andy Q. Yuan; Philip A. Walker; Matthias K. Vorlaender; Siro Bianchi; Barbara Guarino; Anna De Marco; Fabrizia Vanzetta; Gloria Agatic; Mathilde Foglierini; Debora Pinna; Blanca Fernandez-Rodriguez; Alexander Fruehwirth; Chiara Silacci; Roksana W. Ogrodowicz; Stephen R. Martin; Federica Sallusto; JoAnn Suzich; Antonio Lanzavecchia; Qing Zhu; Steven J. Gamblin; John J. Skehel;pmc: PMC4967455
handle: 20.500.11850/118907
Summary Influenza virus remains a threat because of its ability to evade vaccine-induced immune responses due to antigenic drift. Here, we describe the isolation, evolution, and structure of a broad-spectrum human monoclonal antibody (mAb), MEDI8852, effectively reacting with all influenza A hemagglutinin (HA) subtypes. MEDI8852 uses the heavy-chain VH6-1 gene and has higher potency and breadth when compared to other anti-stem antibodies. MEDI8852 is effective in mice and ferrets with a therapeutic window superior to that of oseltamivir. Crystallographic analysis of Fab alone or in complex with H5 or H7 HA proteins reveals that MEDI8852 binds through a coordinated movement of CDRs to a highly conserved epitope encompassing a hydrophobic groove in the fusion domain and a large portion of the fusion peptide, distinguishing it from other structurally characterized cross-reactive antibodies. The unprecedented breadth and potency of neutralization by MEDI8852 support its development as immunotherapy for influenza virus-infected humans. Highlights • Binding to all influenza A subtypes neutralizing seasonal and pandemic strains • Utilizes a rare VH (VH6-1) and carries a low level of somatic mutations • Highly conserved epitope encompassing fusion peptide and hydrophobic groove • Superior therapeutic window compared to oseltamivir in animals Identification of a human monoclonal antibody that reacts effectively with all influenza A hemagglutinin subtypes paves the way for developing immunotherapy for people infected with the flu virus. Graphical Abstract
Cell arrow_drop_down CellArticle . 2016Full-Text: http://europepmc.org/articles/PMC4967455Data sources: PubMed Centraladd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.3929/ethz-b-000118907&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.euAccess RoutesGreen hybrid 318 citations 318 popularity Top 1% influence Top 10% impulse Top 0.1% Powered by BIP!more_vert Cell arrow_drop_down CellArticle . 2016Full-Text: http://europepmc.org/articles/PMC4967455Data sources: PubMed Centraladd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.3929/ethz-b-000118907&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eu