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

doi:10.1016/j.celrep.2023.112402

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

Cell Rep. 2023 Apr 25;42(4):112402. doi: 10.1016/j.celrep.2023.112402. Epub 2023 Apr 15.

Authors

Bronwyn M Gunn¹, Ryan P McNamara², Lianna Wood³, Sabian Taylor⁴, Anush Devadhasan⁴, Wenyu Guo⁴, Jishnu Das⁴, Avlant Nilsson⁵, Amy Shurtleff⁶, Sheri Dubey⁷, Michael Eichberg⁷, Todd J Suscovich⁴, Erica Ollmann Saphire⁸, Douglas Lauffenburger⁵, Beth-Ann Coller⁷, Jakub K Simon⁷, Galit Alter⁴

Affiliations

¹ Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
² Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA. Electronic address: ragonsystemserology@mgh.harvard.edu.
³ Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Division of Gastroenterology, Department of Pediatrics, Boston Children's Hospital, Boston, MA, USA.
⁴ Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
⁵ Division of Gastroenterology, Department of Pediatrics, Boston Children's Hospital, Boston, MA, USA.
⁶ United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD, USA.
⁷ Merck & Co., Inc., Kenilworth, NJ, USA.
⁸ La Jolla Institute for Immunology, La Jolla, CA, USA.

Abstract

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.

Keywords: ADNP; CP: Immunology; Ebola; antibodies; glycoprotein; soluble glycoprotein; vaccine.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Antibodies, Monoclonal
Antibodies, Viral
Ebola Vaccines*
Ebolavirus*
Glycoproteins
Hemorrhagic Fever, Ebola*
Primates
Vaccines, Synthetic

Substances

Ebola Vaccines
Glycoproteins
Antibodies, Viral
Antibodies, Monoclonal
Vaccines, Synthetic

Abstract

Publication types

MeSH terms

Substances

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