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Published on: August 13, 2021
Low-dose multivalent COVID-19 mRNA vaccines enhance broadly cross-reactive antibodies and protective immune responses
Rong Liu1, Lila Patterson2, Mahmuda Yeasmin1
1Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, 30303, USA.
Abstract:
Monovalent and high-dose mRNA vaccines might be associated with limited efficacy and adverse effects, respectively. This study investigated whether a combination of low-dose multivalent mRNA and spike proteins of multiple SARS-CoV-2 variants would enhance broader cross-reactive IgG antibodies and neutralizing activity against SARS-CoV-2. A low-dose of trivalent mRNA vaccines elicited broadly cross-reactive binding IgG antibodies and receptor-binding inhibition activity against various SARS-CoV-2 variants at higher levels than a high-dose monovalent mRNA vaccine. A combination of low-dose trivalent mRNA and spike proteins of multiple SARS-CoV-2 variants further increased the levels of cross-reactive IgG antibodies and neutralizing activity against SARS-CoV-2. Furthermore, coadministration of low doses of SARS-CoV-2 spike mRNA with inactivated split influenza vaccines significantly enhanced immunogenicity and efficacy against influenza.
Insights
Low-dose multivalent mRNA vaccines and spike proteins offer enhanced protection against SARS-CoV-2 variants. This combination strategy improved antibody responses and neutralizing activity compared to high-dose monovalent vaccines.
Area of Science:
- Immunology
- Vaccinology
- Virology
Background:
- Monovalent, high-dose mRNA vaccines may have limitations in efficacy and safety.
- SARS-CoV-2 variants pose ongoing challenges to vaccine effectiveness.
Purpose of the Study:
- To evaluate if combining low-dose multivalent mRNA with spike proteins enhances cross-reactive antibodies and neutralization against SARS-CoV-2.
- To compare this combination strategy against high-dose monovalent mRNA vaccines.
Main Methods:
- Administered low-dose trivalent mRNA vaccines and combinations with multiple SARS-CoV-2 spike proteins.
- Assessed levels of cross-reactive IgG antibodies and neutralizing activity.
- Investigated coadministration with inactivated split influenza vaccines.
Main Results:
- Low-dose trivalent mRNA vaccines induced broader IgG antibodies and receptor-binding inhibition than high-dose monovalent vaccines.
- The combination of low-dose trivalent mRNA and multiple spike proteins further boosted IgG antibodies and neutralizing activity.
- Coadministration with influenza vaccines enhanced immunogenicity and efficacy against influenza.
Conclusions:
- Low-dose multivalent mRNA vaccines combined with multiple SARS-CoV-2 spike proteins represent a promising strategy for broader protection.
- This approach may overcome limitations of current monovalent vaccines against evolving variants.
- Potential for enhanced efficacy when combined with other vaccine types, like influenza vaccines.
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