New variants in the SARS-CoV-2 pandemic are more contagious (Alpha/Delta), evade neutralizing antibodies (Beta), or both (Omicron). This poses a challenge in vaccine development according to WHO. We designed a more universal SARS-CoV-2 DNA vaccine containing receptor-binding domain loops from the huCoV-19/WH01, the Alpha, and the Beta variants, combined with the membrane and nucleoproteins. The vaccine induced spike antibodies crossreactive between huCoV-19/WH01, Beta, and Delta spike proteins that neutralized huCoV-19/WH01, Beta, Delta, and Omicron virus in vitro. The vaccine primed nucleoprotein-specific T cells, unlike spike-specific T cells, recognized Bat-CoV sequences. The vaccine protected mice carrying the human ACE2 receptor against lethal infection with the SARS-CoV-2 Beta variant. Interestingly, priming of cross-reactive nucleoprotein-specific T cells alone was 60% protective, verifying observations from humans that T cells protect against lethal disease. This SARS-CoV vaccine induces a uniquely broad and functional immunity that adds to currently used vaccines.
【초록키워드】 neutralizing antibody, SARS-CoV-2, Vaccine, Vaccine development, pandemic, Immunity, Vaccines, antibody, T cells, Human, variant, Delta, omicron, virus, variants, Spike protein, T cell, mice, membrane, Beta, WHO, DNA vaccine, Protective, cross-reactive, observation, domain, priming, human ACE2 receptor, contagious, lethal disease, lethal infection, neutralized, PROTECT, functional, SARS-CoV vaccine, induce, evade, New, the SARS-CoV-2, 【제목키워드】 neutralizing antibody, SARS-CoV, T cell, DNA vaccine, cross-reactive,