(49d) Characterization of Anti-Fusogenic Monoclonal Antibodies Against Human Coronaviruses

Coronaviruses (CoVs) cause a variety of respiratory and/or enteric tract infections and are noted for their zoonotic potential. The pandemic caused by the severe acute respiratory syndrome CoV-2 (SARS-CoV-2) as well as outbreaks caused by SARS-CoV and MERS-CoV have highlighted the dangers that these zoonotic CoVs pose to human health. CoVs are especially noted for their ability to transmit across species due to variety of strategies they possess in infecting cells. As an example, the CoV S protein, which facilitates receptor binding and membrane fusion, can be cleaved by distinct proteases to expose a fusion peptide (FP) that directly mediates fusion at the plasma membrane surface or at an endosomal membrane. Recently solved Cryo-EM structures have shown that the pre-fusion CoV FP region is exposed and can elicit broadly neutralizing antibodies as it is a well conserved domain across the CoV family. Thus, we designed a novel S antigen incorporating the SARS-CoV pre-fusion FP region as a strategy to generate neutralizing antibodies. This antigen was injected into mice to elicit an immune response and collect antibodies. Functional characterization of these antibodies has determined that they only block SARS-CoV pseudoparticle infection when present during the viral-host cell membrane fusion step. Furthermore, since the CoV FP is well conserved across the CoV family, these antibodies were shown to be cross-reactive against MERS-CoV pseudoparticle infection. We believe this antigen design may present novel strategies towards addressing SARS-CoV-2 and future CoV outbreaks.