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

However, it remains to be determined whether a more limited number of injections of an RBD subunit vaccine would raise a protective response. A key point relevant to this question is that the neutralizing activity elicited in these studies is likely much greater than would be necessary to prevent a new SARS-CoV-2 infection. Rat antisera on average neutralized more efficiently than naive sera bearing 100 µg/ml of ACE2-Ig, which itself neutralizes with an IC50 of less than 1 µg/ml, consistent with its activity against infectious SARS-CoV-1 (Moore et al., 2004) . To provide some context for these numbers, eCD4-Ig, an immunoadhesin that emulates HIV-1 viral receptors and neutralizes with neutralization potency similar to that of ACE2-Ig, affords robust protection against high-dose intravenous challenges with an HIV-1-like virus when it is present in serum in the range of 5-10 µg/ml (Gardner et al., 2019; Gardner et al., 2015) . Thus it is possible that a less robust response could still be protective. Perhaps as important as these quantitative considerations, our data show that the RBD alone is sufficient to elicit a potent neutralizing antibody response. It remains to be determined whether trimer-based vaccines, or trimer/RBD combinations, can be more effective, and whether they carry additional safety concerns.