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

A key remaining question is whether these studies, conducted in rodents, imply that an RBD-based vaccine could be effective in humans. Here experimental details become important. We immunized rats with an adjuvant system (AS01) already in human use, notably for vaccines for shingles (Shingrix TM ) and malaria (Mosquirix TM ). The RBD used here was conjugated to a carrier protein, Keyhole limpet hemocyanin, proven safe over decades in humans (Swaminathan et al., 2014) . However KLH can be problematic for those with shellfish allergies, and alternate scaffolds for presenting the RBD may be necessary. Rats were immunized with two sets of escalating inoculations, each administered over seven days. This strategy has been shown to maximize immune responses against HIV-1 antigens (Tam et al., 2016), but it may not be a practical means of addressing the current pandemic with a subunit vaccine. That said, the escalating dosage strategy used here may more accurately reflect the kinetics of an mRNA-delivered vaccine, and indeed we would argue that an RBD antigen would be a preferable alternative, or at least a useful complement, to mRNA expression of the S-protein trimer.