Abstract

Emerging SARS-CoV-2 variants are the most serious problem for COVID-19 prophylaxis and treatment. To determine whether the SARS-CoV-2 vaccine strain should be updated following variant emergence like seasonal flu vaccine, the changed degree on antigenicity of SARS-CoV-2 variants and H3N2 flu vaccine strains was compared. The neutralization activities of Alpha, Beta and Gamma variants’ spike protein-immunized sera were analysed against the eight current epidemic variants and 20 possible variants combining the top 10 prevalent RBD mutations based on the Delta variant, which were constructed using pseudotyped viruses. Meanwhile, the neutralization activities of convalescent sera and current inactivated and recombinant protein vaccine-elicited sera were also examined against all possible Delta variants. Eight HA protein-expressing DNAs elicited-animal sera were also tested against eight pseudotyped viruses of H3N2 flu vaccine strains from 2011–2019. Our results indicate that the antigenicity changes of possible Delta variants were mostly within four folds, whereas the antigenicity changes among different H3N2 vaccine strains were approximately 10–100-fold. Structural analysis of the antigenic characterization of the SARS-CoV-2 and H3N2 mutations supports the neutralization results. This study indicates that the antigenicity changes of the current SARS-CoV-2 may not be sufficient to require replacement of the current vaccine strain.

Highlights

  • The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), created an unprecedented global public health emergency after it was first reported in December 2019

  • The neutralization activity of the Altered antigenicity of SARS-CoV-2 variants implies changing immunized sera was tested against pseudotyped VOCs and variants of interest (VOIs)

  • We firstly against possible Delta variants constructed 10 possible variants with single high-rate mutations To further illustrate the neutralization effect of SARS-CoV-2 based on the Delta strain, named D1 (N501Y), D2 (E484K), D3 vaccines on possible Delta variants with cumulative amino acid (S477N), D4 (K417T), D5 (N439K), D6 (K417N), D7 (S494P), D8 changes, we examined clinical immune sera following vaccination (E484Q), D9 (F490S), and D10 (A520S)

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Summary

1234567890();,: INTRODUCTION

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), created an unprecedented global public health emergency after it was first reported in December 2019. The neutralization activity of the Altered antigenicity of SARS-CoV-2 variants implies changing immunized sera was tested against pseudotyped VOCs and VOIs. effectiveness of vaccines. We tested the neutralization activity of sera elicited sera against possible Delta variants from animals immunized with the S protein from different VOCs The top 10 mutations in the RBD represent a natural hot-spot of against pseudotyped viruses containing naturally occurring VOCs amino acid changes and might combine with currently circulating and VOIs, as well as 20 possible variants based on the globally variants. We used immunized sera from Alpha, Beta, Gamma, Delta, and we tested sera from recombinant haemagglutinin D614G S protein-immunized animals to test the antigenicity of (HA)-immunized animals for neutralization activity against H3N2 possible variants with RBD hot-spot amino acid changes on the vaccine strains used from 2011–2019. Structural analysis showed that the most variable region of H3N2 HA (A/Victoria/361/2011; PDB code: 4O5N) was located in the globular region, consisting of five classic antigenic sites (Fig. 6b), especially sites A and B near

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