Vaccination with S _pan , an antigen guided by SARS-CoV-2 S protein evolution, protects against challenge with viral variants in mice

Abstract

SARS-CoV-2 continues to accumulate mutations to evade immunity, leading to breakthrough infections after vaccination. How researchers can anticipate the evolutionary trajectory of the virus in advance in the design of next-generation vaccines requires investigation. Here, we performed a comprehensive study of 11,650,487 SARS-CoV-2 sequences, which revealed that the SARS-CoV-2 spike (S) protein evolved not randomly but into directional paths of either high infectivity plus low immune resistance or low infectivity plus high immune resistance. The viral infectivity and immune resistance of variants are generally incompatible, except for limited variants such as Beta and Kappa. The Omicron variant has the highest immune resistance but showed high infectivity in only one of the tested cell lines. To provide cross-clade immunity against variants that undergo diverse evolutionary pathways, we designed a new pan-vaccine antigen (S pan ). S pan was designed by analyzing the homology of 2675 SARS-CoV-2 S protein sequences from the NCBI database before the Delta variant emerged. The refined S pan protein harbors high-frequency residues at given positions that reflect cross-clade generality in sequence evolution. Compared with a prototype wild-type (S wt ) vaccine, which, when administered to mice, induced serum with decreased neutralization activity against emerging variants, S pan vaccination of mice elicited broad immunity to a wide range of variants, including those that emerged after our design. Moreover, vaccinating mice with a heterologous S pan booster conferred complete protection against lethal infection with the Omicron variant. Our results highlight the importance and feasibility of a universal vaccine to fight against SARS-CoV-2 antigenic drift.

Unravelling Antigenic Cross-Reactions toward the World of Coronaviruses: Extent of the Stability of Shared Epitopes and SARS-CoV-2 Anti-Spike Cross-Neutralizing Antibodies

“…However, there are still several possible biases in this hypothesis, since the bat Sarbecovirus remains to be discovered, the cross-reactive immunity reported has not been tested so far for neutralization of SARS-CoV-2, and there is a huge difference between in vitro neutralization of a virus and in vivo protection of humans against this virus. There are still teams that seek to identify a variant-proof strategy for the development of a pan-betacoronaviruses vaccine formulation [ 38 , 171 , 172 , 173 ]. Additional hypotheses refer to as cross-reaction between dengue virus (DENV) antibodies and the SARS-CoV-2 S1 RBD [ 174 ].…”

The rapid rise of SARS‐CoV‐2 Omicron subvariants with immune evasion properties: XBB.1.5 and BQ.1.1 subvariants

“…They engineered seven broadly neutralizing antibodies that are highly effective against all tested variants of SARS-CoV-2, including XBB.1.5 and BQ.1.1. 55 Meanwhile, Zhao et al 56 designed a new pan-vaccine antigen (S pan ) based on the diverse evolution of SARS-CoV-2 spike sequences. It was found that S pan vaccination of mice elicited broad immunity to several variants, including Omicron BA.1.…”

Immunostimulatory nanoparticles go viral

“…Recently, a pan-spike-protein-based vaccine was developed by investigating viral evolution and identifying spike protein consensus sequences that could elicit broadly neutralizing antibodies against circulating strains of the virus and possible future variants. However, further studies to evaluate the efficacy and durability of the immune response are required 10 . An optimal vaccine will ultimately combine innovations in antigen discovery and design with advances in adjuvants and vaccine formulation.…”