In vivo delivery of engineered synthetic DNA-encoded SARS-CoV-2 monoclonal antibodies for pre-exposure prophylaxis in non-human primates

Autor: Ami Patel, Kyle Rosenke, Elizabeth M. Parzych, Friederike Feldmann, Suman Bharti, Amanda J. Griffin, Blake Schouest, Matt Lewis, Jihae Choi, Neethu Chokkalingam, Viviane Machado, Brian J. Smith, Drew Frase, Ali R. Ali, Jamie Lovaglio, Brian Nguyen, Patrick W. Hanley, Susanne N. Walker, Ebony N. Gary, Abhijeet Kulkarni, Allison Generotti, Joseph R. Francica, Kim Rosenthal, Daniel W. Kulp, Mark T. Esser, Trevor R. F. Smith, Carl Shaia, David B. Weiner, Heinz Feldmann
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Emerging Microbes and Infections, Vol 13, Iss 1 (2024)
Druh dokumentu: article
ISSN: 22221751
2222-1751
DOI: 10.1080/22221751.2023.2294860
Popis: ABSTRACTCOVID-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.
Databáze: Directory of Open Access Journals
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