Abstract
The recently emerged Omicron (B.1.1.529) variant has rapidly surpassed Delta to become the predominant circulating SARS-CoV-2 variant, given the higher transmissibility rate and immune escape ability, resulting in breakthrough infections in vaccinated individuals. A new generation of SARS-CoV-2 vaccines targeting the Omicron variant are urgently needed. Here, we developed a subunit vaccine named RBD-HR/trimer by directly linking the sequence of RBD derived from the Delta variant (containing L452R and T478K) and HR1 and HR2 in SARS-CoV-2 S2 subunit in a tandem manner, which can self-assemble into a trimer. In multiple animal models, vaccination of RBD-HR/trimer formulated with MF59-like oil-in-water adjuvant elicited sustained humoral immune response with high levels of broad-spectrum neutralizing antibodies against Omicron variants, also inducing a strong T cell immune response in vivo. In addition, our RBD-HR/trimer vaccine showed a strong boosting effect against Omicron variants after two doses of mRNA vaccines, featuring its capacity to be used in a prime-boost regimen. In mice and non-human primates, RBD-HR/trimer vaccination could confer a complete protection against live virus challenge of Omicron and Delta variants. The results qualified RBD-HR/trimer vaccine as a promising next-generation vaccine candidate for prevention of SARS-CoV-2, which deserved further evaluation in clinical trials.
【초록키워드】 neutralizing antibody, SARS-CoV-2, Vaccine, immune response, vaccination, variant, SARS-CoV-2 variant, Delta, clinical trials, animal models, omicron, delta variant, variants, SARS-CoV-2 vaccine, mRNA vaccines, T cell, Transmissibility, Immune escape, L452R, mice, RBD, non-human primates, vaccine candidate, Breakthrough infection, humoral immune response, B.1.1.529, in vivo, Live virus, dose, T478K, subunit, sequence, trimer, prime-boost regimen, circulating, vaccinated individuals, Complete, SARS-CoV-2 S2, resulting, addition, predominant, elicited, sustained, surpassed, 【제목키워드】 Vaccine, variant, omicron, Protein, protective immunity, trimeric, induce,