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

The 2013 Ebola epidemic in Central and West Africa heralded the emergence of wide-spread, highly patho-genic viruses. The successful recombinant vector vaccine against Ebola (rVSVDG-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.

Automated summary

The 2013 Ebola epidemic in Central and West Africa marked the emergence of highly pathogenic viruses. The successful development of the Ebola vaccine will help control future outbreaks, but understanding how vaccine-induced antibodies protect against infection is crucial.