Lineage-mosaic and mutation-patched spike proteins for broad-spectrum COVID-19 vaccine

Cell Host Microbe. 2022 Dec 14;30(12):1732-1744.e7. doi: 10.1016/j.chom.2022.10.011. Epub 2022 Oct 18.


SARS-CoV-2 spread in humans results in continuous emergence of new variants, highlighting the need for vaccines with broad-spectrum antigenic coverage. Using inter-lineage chimera and mutation-patch strategies, we engineered a recombinant monomeric spike variant (STFK1628x) that contains key regions and residues across multiple SAR-CoV-2 variants. STFK1628x demonstrated high immunogenicity and mutually complementary antigenicity to its prototypic form (STFK). In hamsters, a bivalent vaccine composed of STFK and STFK1628x elicited high titers of broad-spectrum neutralizing antibodies to 19 circulating SARS-CoV-2 variants, including Omicron sublineages BA.1, BA.1.1, BA.2, BA.2.12.1, BA.2.75, and BA.4/5. Furthermore, this vaccine conferred robust protection against intranasal challenges by either SARS-CoV-2 ancestral strain or immune-evasive Beta and Omicron BA.1. Strikingly, vaccination with the bivalent vaccine in hamsters effectively blocked within-cage virus transmission of ancestral SARS-CoV-2, Beta variant, and Omicron BA.1 to unvaccinated sentinels. Thus, our study provided insight and antigen candidates for the development of next-generation COVID-19 vaccines.

Keywords: COVID-19 vaccine; Omicron variants; SARS-CoV-2; broad-spectrum antibodies; variant of concern; virus transmission blocking.

MeSH terms

  • Animals
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Broadly Neutralizing Antibodies
  • COVID-19 Vaccines* / genetics
  • COVID-19* / prevention & control
  • Cricetinae
  • Humans
  • Mutation
  • SARS-CoV-2 / genetics
  • Spike Glycoprotein, Coronavirus / genetics
  • Vaccines, Combined


  • COVID-19 Vaccines
  • spike protein, SARS-CoV-2
  • Spike Glycoprotein, Coronavirus
  • Broadly Neutralizing Antibodies
  • Vaccines, Combined
  • Antibodies, Viral
  • Antibodies, Neutralizing

Supplementary concepts

  • SARS-CoV-2 variants