Abstract
Background: With the continuous emergence of new SARS-CoV-2 variants that feature increased transmission and immune escape, there is an urgent demand for a better vaccine design that will provide broader neutralizing efficacy.
Methods: We report an mRNA-based vaccine using an engineered “hybrid” receptor binding domain (RBD) that contains all 16 point-mutations shown in the currently prevailing Omicron and Delta variants.
Results: A booster dose of hybrid vaccine in mice previously immunized with wild-type RBD vaccine induced high titers of broadly neutralizing antibodies against all tested SARS-CoV-2 variants of concern (VOCs). In naïve mice, hybrid vaccine generated strong Omicron-specific neutralizing antibodies as well as low but significant titers against other VOCs. Hybrid vaccine also elicited CD8+/IFN-γ+ T cell responses against a conserved T cell epitope present in wild type and all VOCs.
Conclusions: These results demonstrate that inclusion of different antigenic mutations from various SARS-CoV-2 variants is a feasible approach to develop cross-protective vaccines.
Keywords: Booster dose; COVID-19; Cross-protectivity; Hybrid vaccine; Next generation vaccine; Omicron vaccine; SARS-CoV-2; Variants of concern; mRNA vaccine.
【저자키워드】 COVID-19, SARS-CoV-2, mRNA vaccine, variants of concern, booster dose, Cross-protectivity, Hybrid vaccine, Next generation vaccine, Omicron vaccine, 【초록키워드】 neutralizing antibody, Efficacy, Vaccine, Mutation, Vaccines, Neutralizing antibodies, mRNA vaccine, Vaccine design, variant, SARS-CoV-2 variant, Delta, Transmission, omicron, variants, Receptor binding domain, T cell, Immune escape, SARS-CoV-2 variants, mice, RBD, T cell responses, VOCs, Neutralizing, epitope, booster dose, wild type, T cell response, Delta variants, hybrid, antigenic, naïve, wild-type, specific neutralizing antibodies, CD8+, mRNA-based vaccine, Inclusion, approach, immunized, new SARS-CoV-2, shown, tested, develop, conserved, feasible, cross-protective, elicited, 【제목키워드】 neutralizing antibody, SARS-CoV-2 variant, Delta, produced,