The SARS-CoV-2 receptor-binding domain elicits a potent neutralizing response without antibody-dependent enhancement

Brian D Quinlan; Huihui Mou; Lizhou Zhang; Yan Gao; Wenhui He; Amrita Ojha; Mark S Parcells; Guangxiang Luo; Wenhui Li; Guocai Zhong; Hyeryun Choe; Michael Farzan

As observed with flaviviruses, there is a qualitative difference between ADE mediated by neutralizing and by non-neutralizing antibodies (Dejnirattisai et al., 2010; Shim et al., 2019; Takada et al., 2003) . In the case of neutralizing antibodies, ADE is a consequence of insufficient coating of the virion surface, due to lower affinity or concentration of the antibody. If concentrations or affinity is raised, neutralization dominates. In contrast, ADE mediated by nonneutralizing antibodies increases with increasing concentration. We therefore speculated that it would be difficult of observe ADE with rat antisera targeting the SARS-CoV-2 RBD, a key neutralizing epitope. Indeed, although rat anti-Zika virus antisera mediated robust ADE of ZIKV in two different Fc receptor-expressing cell lines, no ADE of S-protein pseudoviruses was observed with anti-RBD anti-sera, whether or not the SARS-CoV-2 receptor ACE2 was present.