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Author Spotlight: Advancing Antiviral Strategies Through Novel Immunocapture and Mass Spectrometry Techniques
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Effective vaccination strategy using SARS-CoV-2 spike cocktail against Omicron and other variants of concern
Juan Shi1, Gang Wang1, Jian Zheng2,3
1Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA.
Abstract:
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.
Insights
A new vaccine strategy combining wild-type and Omicron BA1 spike proteins generates strong neutralizing antibodies against multiple SARS-CoV-2 variants, including Omicron subvariants. This approach offers broad protection against COVID-19, addressing vaccine resistance challenges.
Area of Science:
- Virology
- Immunology
- Vaccinology
Background:
- The SARS-CoV-2 Omicron variant possesses over 30 spike protein mutations.
- Omicron subvariants exhibit increased resistance to existing COVID-19 vaccines targeting the original spike protein.
- There is a critical need for vaccines effective against multiple SARS-CoV-2 variants of concern (VOCs).
Purpose of the Study:
- To evaluate the neutralizing activity and protective efficacy of a BA1-S subunit vaccine.
- To assess the impact of combining the BA1-S vaccine with a wild-type S protein (WT-S) vaccine.
- To determine the effectiveness of WT-S/BA1-S as a cocktail or as a prime-boost strategy.
Main Methods:
- Developed a BA1-S subunit vaccine.
- Administered WT-S/BA1-S as a cocktail or as a WT-S prime/BA1-S boost in mice.
- Assessed neutralizing antibody responses against pseudotyped Omicron subvariants (BA1, BA2, BA2.12.1, BA5), other VOCs (Alpha, Beta, Gamma, Delta), original SARS-CoV-2, and SARS-CoV.
- Evaluated protection against a lethal Delta variant challenge.
Main Results:
- A WT-S/BA1-S cocktail or boost induced significantly higher neutralizing antibodies against Omicron subvariants compared to WT-S alone.
- The WT-S/BA1-S strategy also generated potent neutralizing antibodies against other VOCs, SARS-CoV-2, and SARS-CoV.
- WT-S or BA1-S alone did not induce potent neutralizing antibodies against the tested viruses.
- The WT-S/BA1-S cocktail provided complete protection in mice against a lethal Delta variant challenge.
Conclusions:
- A vaccination strategy using a WT-S/BA1-S cocktail or boost elicits potent, broad, and durable neutralizing antibodies.
- This approach is effective against current SARS-CoV-2 Omicron subvariants, other VOCs, and SARS-CoV.
- The findings provide guidance for developing next-generation vaccines to control the COVID-19 pandemic and combat future SARS-CoV-2 variants.
