Systematic Analysis of Monoclonal Antibodies against Ebola Virus GP Defines Features that Contribute to Protection | Zendy

Erica Ollmann Saphire | Zendy; Sharon L. Schendel | Zendy; Marnie L. Fusco | Zendy; Karthik Gangavarapu | Zendy; Bronwyn M. Gunn | Zendy; Anna Z. Wec | Zendy; Peter Halfmann | Zendy; Jennifer M. Brannan | Zendy; Andrew S. Herbert | Zendy; Xiangguo Qiu | Zendy; Kshitij Wagh | Zendy; Shihua He | Zendy; Elena E. Giorgi | Zendy; James Theiler | Zendy; Kathleen B. J. Pommert | Zendy; Tyler B. Krause | Zendy; Hannah L. Turner | Zendy; Charles D. Murin | Zendy; Jesper Pallesen | Zendy; Edgar Davidson | Zendy; Rafi Ahmed | Zendy; M. Javad Aman | Zendy; Alexander Bukreyev | Zendy; Dennis R. Burton | Zendy; James E. Crowe | Zendy; Carl W. Davis | Zendy; George Georgiou | Zendy; Florian Krammer | Zendy; Christos A. Kyratsous | Zendy; Jonathan R. Lai | Zendy; Cory L. Nykiforuk | Zendy; Michael Pauly | Zendy; Pramila Rijal | Zendy; Ayato Takada | Zendy; Alain Townsend | Zendy; Viktor E. Volchkov | Zendy; Laura M. Walker | Zendy; ChengI Wang | Zendy; Larry Zeitlin | Zendy; Benjamin J. Doranz | Zendy; Andrew B. Ward | Zendy; Bette Korber | Zendy; Gary Kobinger | Zendy; Kristian G. Andersen | Zendy; Yoshihiro Kawaoka | Zendy; Galit Alter | Zendy; Kartik Chandran | Zendy; John M. Dye | Zendy

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Systematic Analysis of Monoclonal Antibodies against Ebola Virus GP Defines Features that Contribute to Protection

Author(s) -

Erica Ollmann Saphire,

Sharon L. Schendel,

Marnie L. Fusco,

Karthik Gangavarapu,

Bronwyn M. Gunn,

Anna Z. Wec,

Peter Halfmann,

Jennifer M. Brannan,

Andrew S. Herbert,

Xiangguo Qiu,

Kshitij Wagh,

Shihua He,

Elena E. Giorgi,

James Theiler,

Kathleen B. J. Pommert,

Tyler B. Krause,

Hannah L. Turner,

Charles D. Murin,

Jesper Pallesen,

Edgar Davidson,

Rafi Ahmed,

M. Javad Aman,

Alexander Bukreyev,

Dennis R. Burton,

James E. Crowe,

Carl W. Davis,

George Georgiou,

Florian Krammer,

Christos A. Kyratsous,

Jonathan R. Lai,

Cory L. Nykiforuk,

Michael Pauly,

Pramila Rijal,

Ayato Takada,

Alain Townsend,

Viktor E. Volchkov,

Laura M. Walker,

ChengI Wang,

Larry Zeitlin,

Benjamin J. Doranz,

Andrew B. Ward,

Bette Korber,

Gary Kobinger,

Kristian G. Andersen,

Yoshihiro Kawaoka,

Galit Alter,

Kartik Chandran,

John M. Dye

Publication year - 2018

Publication title -

cell

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 26.304

H-Index - 776

eISSN - 1097-4172

pISSN - 0092-8674

DOI - 10.1016/j.cell.2018.07.033

Subject(s) - epitope , ebola virus , biology , virology , monoclonal antibody , neutralization , antibody , ebolavirus , glycoprotein , glycan , epitope mapping , immune system , virus , immunology , microbiology and biotechnology

Antibodies are promising post-exposure therapies against emerging viruses, but which antibody features and in vitro assays best forecast protection are unclear. Our international consortium systematically evaluated antibodies against Ebola virus (EBOV) using multidisciplinary assays. For each antibody, we evaluated epitopes recognized on the viral surface glycoprotein (GP) and secreted glycoprotein (sGP), readouts of multiple neutralization assays, fraction of virions left un-neutralized, glycan structures, phagocytic and natural killer cell functions elicited, and in vivo protection in a mouse challenge model. Neutralization and induction of multiple immune effector functions (IEFs) correlated most strongly with protection. Neutralization predominantly occurred via epitopes maintained on endosomally cleaved GP, whereas maximal IEF mapped to epitopes farthest from the viral membrane. Unexpectedly, sGP cross-reactivity did not significantly influence in vivo protection. This comprehensive dataset provides a rubric to evaluate novel antibodies and vaccine responses and a roadmap for therapeutic development for EBOV and related viruses.

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