Published on Tue Aug 10 2021

Antibody mediated neutralization of authentic SARS-CoV-2 B.1.617 variants harboring L452R and T478K/E484Q

Wilhelm, A., Toptan, T., Pallas, C., Wolf, T., Goetsch, U., Gottschalk, R., Vehreschild, M. J., Ciesek, S., Widera, M.

authentic SARS-CoV-2 variants harboring the spike substitution L452R had reduced susceptibility to convalescent and vaccine-elicited sera and mAbs. Kappa and Delta showed a reduced neutralization by convalescence by a factor of 5.71 and 3.64, respectively. Delta was resistant to imdevimab, which

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Abstract

The capacity of convalescent and vaccine-elicited sera and monoclonal antibodies (mAb) to neutralize SARS-CoV-2 variants is currently of high relevance to assess the protection against infections. We performed a cell culture-based neutralization assay focusing on authentic SARS-CoV-2 variants B.1.617.1 (Kappa), B.1.617.2 (Delta), B.1.427/B.1.429 (Epsilon), all harboring the spike substitution L452R. We found that authentic SARS-CoV-2 variants harboring L452R had reduced susceptibility to convalescent and vaccine-elicited sera and mAbs. Compared to B.1, Kappa and Delta showed a reduced neutralization by convalescent sera by a factor of 5.71 and 3.64, respectively, which constitutes a 2-fold greater reduction when compared to Epsilon. BNT2b2 and mRNA1273 vaccine-elicited sera were less effective against Kappa, Delta, and Epsilon compared to B.1. No difference was observed between Kappa and Delta towards vaccine-elicited sera, whereas convalescent sera were 1.6-fold less effective against Delta, respectively. Both B.1.617 variants Kappa (+E484Q) and Delta (+T478K) were less susceptible to either casirivimab or imdevimab. In conclusion, in contrast to the parallel circulating Kappa variant, the neutralization efficiency of convalescent and vaccine-elicited sera against Delta was moderately reduced. Delta was resistant to imdevimab, which however, might be circumvented by a combination therapy with casirivimab together.