Cross-Reactive and Potent Neutralizing Antibody Responses in Human Survivors of Natural Ebolavirus Infection

Recent studies have suggested that antibody-mediated protection against the Ebolaviruses may be achievable, but little is known about whether or not antibodies can confer cross-reactive protection against viruses belonging to diverse Ebolavirus species, such as Ebola virus (EBOV), Sudan virus (SUDV), and Bundibugyo virus (BDBV). We isolated a large panel of human monoclonal antibodies (mAbs) against BDBV glycoprotein (GP) using peripheral blood B cells from survivors of the 2007 BDBV outbreak in Uganda. We determined that a large proportion of mAbs with potent neutralizing activity against BDBV bind to the glycan cap and recognize diverse epitopes within this major antigenic site. We identified several glycan cap-specific mAbs that neutralized multiple ebolaviruses, including SUDV, and a cross-reactive mAb that completely protected guinea pigs from the lethal challenge with heterologous EBOV. Our results provide a roadmap to develop a single antibody-based treatment effective against multiple Ebolavirus infections. [Display omitted] •Natural Ebolavirus infection induced B cells encoding cross-reactive antibodies•Some cross-reactive human antibodies neutralized multiple Ebolavirus species•A large proportion of BDBV-neutralizing antibodies bound to the glycan cap•Glycan cap-specific antibodies exhibited very potent neutralizing activity Natural Ebola virus infection causes the induction of B cells that encode potent neutralizing human antibodies, which possess, in some cases, a surprising level of cross-reactivity for multiple species of filoviruses. The neutralizing antibody repertoire recognizes diverse features on the surface glycoprotein, but most of the potent antibodies recognize the glycan cap region.