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
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.
