Limited neutralization of authentic SARS-CoV-2 variants carrying E484K in vitro.
Ontology highlight
ABSTRACT:
SUBMITTER: Widera M
PROVIDER: S-EPMC8344430 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description: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 8.00 and 5.33, 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 1.51-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 combination therapy with casirivimab together.
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Project description:Fast-spreading variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) energize the COVID-19 pandemic. While viral infections elicit a conserved immune response, it is not known whether SARS-CoV-2 variants, which display reduced neutralizing activity by vaccine-elicited antibodies, prompt specific genomic immune responses. To test this, we generated and investigated the transcriptomes in PBMCs from hospitalized patients infected with either the Alpha variant (n=36) or with the Alpha variant that had acquired the E484K escape mutation (Alpha+E484K) (n=13). We identified a gene module preferentially activated in patients infected with the Alpha+E484K variant and in patients infected with the Alpha (n=9) and Gamma (n=3) variants that also carry by the E484K escape mutation. The E484K signature was enriched for genes preferentially expressed in monocytes and linked to severe viral infection. However, both cohorts had undergone similar treatments and no differences in disease severity were reported suggesting that this signature reflects a variant response and does not necessarily associate with disease outcome. Additionally, longitudinal transcriptome analyses revealed a more persistent retention of immune signatures in Alpha+E484K patients throughout the entire course of COVID-19 disease and convalescence. While the OAS1 Neanderthal mutation has been linked to a milder COVID-19 pathology, we did not identify significant immune transcriptomes differences in the 25 patients homozygous for this mutation. Our study offers insights into distinct molecular immune responses elicited by SARS-CoV-2 variants carrying the E484K escape mutation throughout the COVID-19 disease.
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