Vaccine monitoring shows that focused immunization with SARS-CoV-2 receptor-binding domain provides a better neutralizing antibody response than full-length spike protein

Abstract

Effective tools to monitor SARS-CoV-2 transmission and humoral immune responses are highly needed. Protective humoral immunity involves neutralizing antibodies and will be a hallmark for the evaluation of a vaccine response efficacy. Here we present a sensitive, fast and simple neutralization ELISA method to determine the levels of antibody-mediated virus neutralization. We can show that it is strongly correlated with the more elaborate plaque reduction neutralization test (PRNT) (ρ = 0.9231, p < 0.0001). Furthermore, we present pre-clinical vaccine models using recombinant receptor binding domain (RBD) and full-length spike antigen as immunogens showing a profound antibody neutralization capacity that exceeds the highest neutralization titers from convalescent individuals. Using a panel of novel high-affinity murine monoclonal antibodies (mAbs) we also show that majority of the RBD-raised mAbs have inhibitory properties while only a few of the spike-raised mAbs do. In conclusion, the ELISA-based viral neutralization test offers a time- and cost-effective alternative to the PRNT. The immunization results indicate that vaccine strategies focused only on the RBD region may have major advantages over those based on the full spike sequence.

Reply to Lassaunière: On the functional characterization of the Y453F RBD variant found in cluster 5 SARS-CoV-2

“…Because neutralizing antibodies preferentially localize to the RBD ( 2 ) and the high degree of correlation between our neutralization ELISA and the plaque reduction neutralization test (PRNT) ( 3 ), we conclude that the cluster-5 Y453F-RBD has a minor evasive advantage.…”