Effective vaccination strategy using SARS-CoV-2 spike cocktail against Omicron and other variants of concern

Juan Shi, Gang Wang, Jian Zheng, Abhishek K. Verma, Xiaoqing Guan, Moffat M. Malisheni, Qibin Geng, Fang Li, Stanley Perlman, Lanying Du

Research output: Contribution to journalArticlepeer-review


The SARS-CoV-2 Omicron variant harbors more than 30 mutations in its spike (S) protein. Circulating Omicron subvariants, particularly BA5 and other variants of concern (VOCs), show increased resistance to COVID-19 vaccines that target the original S protein, calling for an urgent need for effective vaccines to prevent multiple SARS-CoV-2 VOCs. Here, we evaluated the neutralizing activity and protection conferred by a BA1-S subunit vaccine when combined with or used as booster doses after, administration of wild-type S protein (WT-S). A WT-S/BA1-S cocktail, or WT-S prime and BA1-S boost, induced significantly higher neutralizing antibodies against pseudotyped Omicron BA1, BA2, BA2.12.1, and BA5 subvariants, and similar or higher neutralizing antibodies against the original SARS-CoV-2, than the WT-S protein alone. The WT-S/BA1-S cocktail also elicited higher or significantly higher neutralizing antibodies than the WT-S-prime-BA1-S boost, WT-S alone, or BA1-S alone against pseudotyped SARS-CoV-2 Alpha, Beta, Gamma, and Delta VOCs, and SARS-CoV, a closely related beta-coronavirus using the same receptor as SARS-CoV-2 for viral entry. By contrast, WT-S or BA1-S alone failed to induce potent neutralizing antibodies against all these viruses. Similar to the WT-S-prime-BA1-S boost, the WT-S/BA1-S cocktail completely protected mice against the lethal challenge of a Delta variant with negligible weight loss. Thus, we have identified an effective vaccination strategy that elicits potent, broadly, and durable neutralizing antibodies against circulating SARS-CoV-2 Omicron subvariants, other VOCs, original SARS-CoV-2, and SARS-CoV. These results will provide useful guidance for developing efficacious vaccines that inhibit current and future SARS-CoV-2 variants to control the COVID-19 pandemic.

Original languageEnglish (US)
Article number169
Journalnpj Vaccines
Issue number1
StatePublished - Dec 2022

Bibliographical note

Funding Information:
This study was supported by NIH grants (R01AI157975, R01AI139092, and R01AI137472).

Publisher Copyright:
© 2022, The Author(s).

PubMed: MeSH publication types

  • Journal Article


Dive into the research topics of 'Effective vaccination strategy using SARS-CoV-2 spike cocktail against Omicron and other variants of concern'. Together they form a unique fingerprint.

Cite this