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EMBO Mol Med ; 14(10): e15821, 2022 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-35986481

RESUMO

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.


Assuntos
COVID-19 , Vacinas de DNA , Vacinas Virais , Enzima de Conversão de Angiotensina 2/genética , Animais , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Humanos , Camundongos , Nucleoproteínas , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus/genética , Linfócitos T , Vacinas de DNA/genética , Proteínas do Envelope Viral/química , Proteínas do Envelope Viral/genética , Vacinas Virais/genética
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