Abstract
Facing the imminent need for vaccine candidates with cross-protection against globally circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutants, we present a conserved antigenic peptide RBD9.1 with both T-cell and B-cell epitopes. RBD9.1 can be recognized by coronavirus disease 2019 (COVID-19) convalescent serum, particularly for those with high neutralizing potency. Immunization with RBD9.1 can successfully induce the production of the receptor-binding domain (RBD)-specific antibodies in Balb/c mice. Importantly, the immunized sera exhibit sustained neutralizing efficacy against multiple dominant SARS-CoV-2 variant strains, including B.1.617.2 that carries a point mutation (SL452R) within the sequence of RBD9.1. Specifically, SY451 and SY454 are identified as the key amino acids for the binding of the induced RBD-specific antibodies to RBD9.1. Furthermore, we have confirmed that the RBD9.1 antigenic peptide can induce a S448-456 (NYNYLYRLF)-specific CD8+ T-cell response. Both RBD9.1-specific B cells and the S448-456-specific T cells can still be activated more than 3 months post the last immunization. This study provides a potential vaccine candidate that can generate long-term protective efficacy over SARS-CoV-2 variants, with the unique functional mechanism of activating both humoral and cellular immunity.
Highlights
Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be the most effective way to improve the current social distancing resulting from protective measures and to recover from economic damage [1]
Correlation study confirmed that the amounts of RBD9.1 binding antibodies of individual samples were positively correlated with their neutralizing capability, represented by the receptor-binding domain (RBD)-hACE2 interaction inhibition titer (IC50) or the SARS-CoV-2 pseudovirus neutralization titer (IC50), respectively (Figures 1D, E)
No differences were observed for the neutralizing capability among convalescent sera from patients of different ages and genders (Supplementary Figures 1B, C). These results suggested that COVID-19 convalescent sera with high binding ability to RBD9.1 exhibited marked neutralizing capability against SARS-CoV-2 pseudovirus
Summary
Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be the most effective way to improve the current social distancing resulting from protective measures and to recover from economic damage [1]. Available coronavirus disease 2019 (COVID-19) vaccines include recombinant proteins, RNA vectors, virus-like particles (VLPs), and inactivated virus. All of these share the neutralizing mechanism to produce antibody responses against the wild-type Spike (S) protein of SARS-CoV-2 [11,12,13,14,15]. New generations of vaccines based on conservative sequences within regions that are responsible for the RBD–ACE2 interaction surface are urgent and necessary
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