Human coronaviruses such as SARS-CoV, MERS-CoV, and SARS-CoV-2 have recurrently emerged as significant pathogens, causing severe respiratory illnesses and presenting challenges to monoclonal antibody therapeutics due to their rapid evolution, particularly the diverse variants of SARS-CoV-2. In this study, we utilized "Knob-into-Hole" and "IgG-scFv" technologies to engineer bispecific antibodies (bsAbs) that target both the viral receptor and spike protein, enhancing their neutralization breadth and potency. Our bsAbs, combining anti-SARS-CoV-2 or anti-MERS-CoV antibodies with an anti-ACE2 antibody, demonstrated effective neutralization across a range of SARS-CoV-2 variants, SARS-CoV and MERS-CoV in both pseudovirus and authentic virus assays. Notably, the "IgG-scFv" bsAbs format exhibited superior binding and neutralization capabilities compared to the "Knob-into-Hole" configurations. The most effective of these, "IgG-scFv" H11B11_m336, displayed exceptional neutralization potency against a panel of 24 pseudotyped Beta-Coronaviruses, with IC₅₀ values ranging from 0.001-0.183 μg/mL. Overall, our findings underscore the potential of bsAbs as an effective strategy to meet the immediate challenges posed by existing and emerging pathogens, thereby enhancing global pandemic preparedness.

2024-12-31·Emerging microbes & infections

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

Article

作者: Parzych, Elizabeth M. ; Lewis, Matt ; Ali, Ali R. ; Nguyen, Brian ; Kulkarni, Abhijeet ; Feldmann, Friederike ; Esser, Mark T. ; Francica, Joseph R. ; Choi, Jihae ; Rosenke, Kyle ; Schouest, Blake ; Rosenthal, Kim ; Griffin, Amanda J. ; Kulp, Daniel W. ; Chokkalingam, Neethu ; Lovaglio, Jamie ; Feldmann, Heinz ; Machado, Viviane ; Shaia, Carl ; Hanley, Patrick W. ; Walker, Susanne N. ; Weiner, David B. ; Generotti, Allison ; Patel, Ami ; Smith, Trevor R. F. ; Frase, Drew ; Bharti, Suman ; Smith, Brian J. ; Gary, Ebony N.

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.

2024-12-01·Clinical and Experimental Nephrology

Effects of anti-SARS-CoV-2 vaccination in living kidney transplant recipients prior to transplantation

Letter

作者: Terada, Mari ; Tomita, Yusuke ; Uehara, Saeko ; Yamamoto, Norio ; Nakamura, Michio

100 项与 ETH-46 相关的药物交易

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