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Emerg Microbes Infect ; 13(1): 2294860, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38165394

RESUMO

COVID-19 remains a major public health concern. Monoclonal antibodies have received emergency use authorization (EUA) for pre-exposure prophylaxis against COVID-19 among high-risk groups for treatment of mild to moderate COVID-19. In addition to recombinant biologics, engineered synthetic DNA-encoded antibodies (DMAb) are an important strategy for direct in vivo delivery of protective mAb. A DMAb cocktail was synthetically engineered to encode the immunoglobulin heavy and light chains of two different two different Fc-engineered anti-SARS-CoV-2 antibodies. The DMAbs were designed to enhance in vivo expression and delivered intramuscularly to cynomolgus and rhesus macaques with a modified in vivo delivery regimen. Serum levels were detected in macaques, along with specific binding to SARS-CoV-2 spike receptor binding domain protein and neutralization of multiple SARS-CoV-2 variants of concern in pseudovirus and authentic live virus assays. Prophylactic administration was protective in rhesus macaques against signs of SARS-CoV-2 (USA-WA1/2020) associated disease in the lungs. Overall, the data support further study of DNA-encoded antibodies as an additional delivery mode for prevention of COVID-19 severe disease. These data have implications for human translation of gene-encoded mAbs for emerging infectious diseases and low dose mAb delivery against COVID-19.


Assuntos
COVID-19 , Profilaxia Pré-Exposição , Animais , Macaca mulatta , COVID-19/prevenção & controle , SARS-CoV-2/genética , Anticorpos Antivirais , Anticorpos Monoclonais , Macaca fascicularis , DNA , Anticorpos Neutralizantes , Glicoproteína da Espícula de Coronavírus/genética
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