Potent neutralizing monoclonal antibodies against Ebola virus isolated from vaccinated donors

Abstract

Ebola virus (EBOV) can cause severe hemorrhagic fever in humans, and no approved treatment is currently available. Although several antibodies have achieved good protection in animal models, the potential emerging isolates of ebolavirus and the unknown effects of experimental antibodies in humans underscore the need to develop additional antibodies to address the threat of Ebola. Here, we isolated a series of memory B cell-derived monoclonal antibodies from healthy Chinese adults vaccinated with Ad5-EBOV. These antibodies were encoded by diverse germline genes and had high levels of somatic hypermutation. Most antibodies were cross-reactive and could bind at least two ebolavirus glycoproteins (GPs). Seven neutralizing antibodies were identified using HIV-EBOV GP-Luc pseudovirus, and they effectively neutralized authentic EBOV. In particular, monoclonal antibody 2G1 exhibited potent cross-neutralization against HIV-EBOV/SUDV/BDBV GP-Luc bearing different ebolavirus GPs. We used truncated GPs, competition assays, and software prediction to analyze seven neutralizing antibodies, which bound four different epitopes on GP. Importantly, three of these antibodies provided complete protection in mice when administered one day post-infection. Our study expands the list of candidate antibodies and the options for successfully treating ebolavirus infection.

Human-IgG-Neutralizing Monoclonal Antibodies Block the SARS-CoV-2 Infection

“…All the positive clones were then sequenced. Notably, almost all (98.6%) of the sequences obtained were unique ones (Figure 2B), similar to what were previously reported in Ebola (Fan et al, 2020;Zhang et al, 2016) and yellow fever (Calvert et al, 2016) studies.…”

Development of Patient-Derived Human Monoclonal Antibodies Against Nucleocapsid Protein of Severe Acute Respiratory Syndrome Coronavirus 2 for Coronavirus Disease 2019 Diagnosis

“…Competitiveness is defined by the values of competition percentages calculated by the given formula. A paired antibodies are defined as non-competing if the value is less than 20%, are deemed to compete the same epitope if the value is greater than 60%, and are considered a part of overlapping if the value is between 20 and 60 (29). Based on the data of competition, all the candidate antibodies can be roughly divided into five groups.…”

Prepare for the Future: Dissecting the Spike to Seek Broadly Neutralizing Antibodies and Universal Vaccine for Pandemic Coronaviruses

“…Data from HIV-1 gp41 aided the identification of a conserved site within ebolavirus GP2 that can be recognized by bnAbs, the HR2/MPER ( Flyak et al, 2018 ). Recently 2G1, a GP2-specific bnAb isolated from a vaccinated individual, exhibited cross-neutralization against EBOV, BDVD and SUDV ( Fan et al, 2020 ), opening the possibility to develop pan-ebolavirus vaccines and antibody cocktails ( Gilchuk et al, 2020 ).…”