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
Author Information
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. Electronic address: ragonsystemserology@mgh.harvard.edu.
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.
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.
