A booster dose of Delta × Omicron hybrid mRNA vaccine produced broadly neutralizing antibody against Omicron and other SARS-CoV-2 variants

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.

Omicron targets upper airways in pediatrics, elderly and unvaccinated population

“…Lee et al [ 13 ] discussed that only vaccine schedules with at least one mRNA vaccine and a booster dose would trigger a sufficient neutralization response against Omicron.…”

Multivalent Human Cytomegalovirus Glycoprotein B Nucleoside-Modified mRNA Vaccines Demonstrate a Greater Breadth in T cell but not Antibody Responses

“…A recent study showed that the SARS-CoV-2 mRNA-LNP vaccine boost in naïve individuals elicited an increased plasma neutralizing antibody response but a variable antibody response breadth compared to the convalescent individuals 72 . Since the inclusion of the Omicron variant provided minimal gains in protective efficacy against new SARS-CoV-2 strains, their impact on the SARS-CoV-2 pandemic remains unknown [73][74][75][76] . While the B cell response breadth against HCMV gB did not benefit from multivalent vaccines in these studies, a higher magnitude T cell response was elicited against monovalent vaccine-mismatched gB genotype, implying that the multivalent HCMV glycoprotein immunization should be considered as a strategy for those vaccines that seek to enhance T cell response breadth.…”

COVID-19 vaccine update: vaccine effectiveness, SARS-CoV-2 variants, boosters, adverse effects, and immune correlates of protection

“…Additionally, the timing of boosting should be optimized, as preexisting immunity may compromise the effect of the booster dose [ 130 , 242 ]. Notably, animal studies also found Omicron-specific vaccines induced potent antibodies and immunity against Omicron but not the ancestral strain in vaccine-naive mice and Syrian hamsters [ 241 – 243 ]. A serological study of vaccine-naive individuals infected with Omicron also showed that their sera contain nAbs against Omicron but not the other variants [ 244 ].…”