Antibodies against the Ebola virus soluble glycoprotein are associated with long-term vaccine-mediated protection of non-human primates

Bronwyn M. Gunn; Ryan P. McNamara; Lianna Wood; Sabian Taylor; Anush Devadhasan; Wenyu Guo; Jishnu Das; Avlant Nilsson; Amy Shurtleff; Sheri Dubey; Michael Eichberg; Todd J. Suscovich; Erica Ollmann Saphire; Douglas Lauffenburger; Beth-Ann Coller; Jakub K. Simon; Galit Alter

Cell Reports (Apr 2023)

Antibodies against the Ebola virus soluble glycoprotein are associated with long-term vaccine-mediated protection of non-human primates

Bronwyn M. Gunn,
Ryan P. McNamara,
Lianna Wood,
Sabian Taylor,
Anush Devadhasan,
Wenyu Guo,
Jishnu Das,
Avlant Nilsson,
Amy Shurtleff,
Sheri Dubey,
Michael Eichberg,
Todd J. Suscovich,
Erica Ollmann Saphire,
Douglas Lauffenburger,
Beth-Ann Coller,
Jakub K. Simon,
Galit Alter

Affiliations

Bronwyn M. Gunn: Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA
Ryan P. McNamara: Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Corresponding author
Lianna Wood: Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Division of Gastroenterology, Department of Pediatrics, Boston Children’s Hospital, Boston, MA, USA
Sabian Taylor: Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA
Anush Devadhasan: Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA
Wenyu Guo: Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA
Jishnu Das: Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA
Avlant Nilsson: Division of Gastroenterology, Department of Pediatrics, Boston Children’s Hospital, Boston, MA, USA
Amy Shurtleff: United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD, USA
Sheri Dubey: Merck & Co., Inc., Kenilworth, NJ, USA
Michael Eichberg: Merck & Co., Inc., Kenilworth, NJ, USA
Todd J. Suscovich: Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA
Erica Ollmann Saphire: La Jolla Institute for Immunology, La Jolla, CA, USA
Douglas Lauffenburger: Division of Gastroenterology, Department of Pediatrics, Boston Children’s Hospital, Boston, MA, USA
Beth-Ann Coller: Merck & Co., Inc., Kenilworth, NJ, USA
Jakub K. Simon: Merck & Co., Inc., Kenilworth, NJ, USA
Galit Alter: Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA

Journal volume & issue: Vol. 42, no. 4
p. 112402

Abstract

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Summary: The 2013 Ebola epidemic in Central and West Africa heralded the emergence of wide-spread, highly pathogenic viruses. The successful recombinant vector vaccine against Ebola (rVSVΔG-ZEBOV-GP) will limit future outbreaks, but identifying mechanisms of protection is essential to protect the most vulnerable. Vaccine-induced antibodies are key determinants of vaccine efficacy, yet the mechanism by which vaccine-induced antibodies prevent Ebola infection remains elusive. Here, we exploit a break in long-term vaccine efficacy in non-human primates to identify predictors of protection. Using unbiased humoral profiling that captures neutralization and Fc-mediated functions, we find that antibodies specific for soluble glycoprotein (sGP) drive neutrophil-mediated phagocytosis and predict vaccine-mediated protection. Similarly, we show that protective sGP-specific monoclonal antibodies have elevated neutrophil-mediated phagocytic activity compared with non-protective antibodies, highlighting the importance of sGP in vaccine protection and monoclonal antibody therapeutics against Ebola virus.

CP: Immunology

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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