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

• Published in: npj vaccines 2022-12, Vol.7 (1), p.169-169, Article 169
• Main Authors: Shi, Juan, Wang, Gang, Zheng, Jian, Verma, Abhishek K., Guan, Xiaoqing, Malisheni, Moffat M., Geng, Qibin, Li, Fang, Perlman, Stanley, Du, Lanying
• Format: Article
• Language: English
• Subjects: 631/326/590/2294; 631/326/596/4130; Biomedical and Life Sciences; Biomedicine; Infectious Diseases; Medical Microbiology; Public Health; Vaccine; Virology
• ISSN: 2059-0105; 2059-0105
• DOI: 10.1038/s41541-022-00580-z

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.