Protective prototype-Beta and Delta-Omicron chimeric RBD-dimer vaccines against SARS-CoV-2

TLDR

Breakthrough infections by SARS‑CoV‑2 variants pose a global challenge for pandemic control, and a prototype subunit vaccine ZF2001 based on a dimeric receptor‑binding domain has been previously developed. The study aims to develop a chimeric RBD‑dimer vaccine that can be rapidly adapted to SARS‑CoV‑2 variants, including prototype‑Beta and Delta‑Omicron versions. The authors designed prototype‑Beta and Delta‑Omicron chimeric RBD‑dimers and evaluated their immunogenicity and protective efficacy in mice and macaques. These chimeric vaccines elicited broader neutralizing antibody responses and superior protection in mice and macaques compared to homotypic vaccines, supporting rapid multivalent vaccine updates against circulating variants.

Abstract

Breakthrough infections by SARS-CoV-2 variants become the global challenge for pandemic control. Previously, we developed the protein subunit vaccine ZF2001 based on the dimeric receptor-binding domain (RBD) of prototype SARS-CoV-2. Here, we developed a chimeric RBD-dimer vaccine approach to adapt SARS-CoV-2 variants. A prototype-Beta chimeric RBD-dimer was first designed to adapt the resistant Beta variant. Compared with its homotypic forms, the chimeric vaccine elicited broader sera neutralization of variants and conferred better protection in mice. The protection of the chimeric vaccine was further verified in macaques. This approach was generalized to develop Delta-Omicron chimeric RBD-dimer to adapt the currently prevalent variants. Again, the chimeric vaccine elicited broader sera neutralization of SARS-CoV-2 variants and conferred better protection against challenge by either Delta or Omicron SARS-CoV-2 in mice. The chimeric approach is applicable for rapid updating of immunogens, and our data supported the use of variant-adapted multivalent vaccine against circulating and emerging variants.