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

One concern associated with coronavirus vaccines is the possibility that anti-S-protein antibodies could increase the efficiency of infection of cells, such as alveolar macrophages, expressing Fc receptors, for example FcγRI (CD64) or FcγRII (CD32). This undesirable antibody-dependent enhancement (ADE) has been well characterized in tissue-culture studies of several flaviviruses including Zika virus (ZIKV) and dengue virus (Shim et al., 2019) . To evaluate this possibility for SARS-CoV-2, SARS2-PV were mixed with pooled day-0 or day-40 serum at the indicated serial dilutions, and the resulting virus/sera mixtures were incubated with HEK293T cells transfected to express rat FcγRI. These cells did not express ACE2 and no infection was observed with day-0 preimmune sera nor day-40 immune sera ( Figure 3A ). To verify that these cells were capable of mediating ADE, rat anti-ZIKV antisera generated by two different rats and pooled, or day-0 preimmune sera was incubated at the same dilutions with ZIKV virus-like particles (VLP). In contrast to the absence of effect of day-40 anti-RBD anti-sera on SARS2-PV, anti-ZIKV antisera at the same concentrations promoted robust ADE ( Figure 3B ). ADE activity peaked at approximately a 1/2000 dilution, consistent with competition between ADE and neutralizing activities of these antisera.