A spike-trimer protein-based tetravalent COVID-19 vaccine elicits enhanced breadth of neutralization against SARS-CoV-2 Omicron subvariants and other variants

Multivalent vaccines combining crucial mutations from phylogenetically divergent variants could be an effective approach to defend against existing and future SARS-Co V-2 variants.In this study,we developed a tetravalent COVID-19 vaccine SCTV01E,based on the trimeric Spike protein of SARS-Co V-2 variants Alpha,Beta,Delta,and Omicron BA.1,with a squalenebased oil-in-water adjuvant SCT-VA02B.In the immunogenicity studies in na?ve BALB/c and C57BL/6J mice,SCTV01E exhibited the most favorable immunogenic characteristics to induce balanced and broad-spectrum neutralizing potencies against pre-Omicron variants(D614G,Alpha,Beta,and Delta)and newly emerging Omicron subvariants(BA.1,BA.1.1,BA.2,BA.3,and BA.4/5).Booster studies in C57BL/6J mice previously immunized with D614G monovalent vaccine demonstrated superior neutralizing capacities of SCTV01E against Omicron subvariants,compared with the D614G booster regimen.Furthermore,SCTV01E vaccination elicited na?ve and central memory T cell responses to SARS-Co V-2 ancestral strain and Omicron spike peptides.Together,our comprehensive immunogenicity evaluation results indicate that SCTV01E could become an important COVID-19 vaccine platform to combat surging infections caused by the highly immune evasive BA.4/5 variants.SCTV01E is currently being studied in a head-to-head immunogenicity comparison phase 3 clinical study with inactivated and m RNA vaccines(NCT05323461).