Tweet
Nat Microbiol
. 2025 Mar 17.
doi: 10.1038/s41564-025-01955-3. Online ahead of print. Drug-Fc conjugate CD388 targets influenza virus neuraminidase and is broadly protective in mice
Simon Döhrmann # 1 , James Levin # 1 , Jason N Cole # 1 , Allen Borchardt # 1 , Karin Amundson 1 , Amanda Almaguer 1 , Elizabeth Abelovski 1 , Rajvir Grewal 1 , Douglas Zuill 1 , Nicholas Dedeic 1 , Grayson Hough 1 , Joanne Fortier 1 , Joanna Donatelli 1 , Thanh Lam 1 , Zhi-Yong Chen 1 , Wanlong Jiang 1 , Travis Haussener 1 , Alain Noncovich 1 , James M Balkovec 1 , Daniel C Bensen 1 , Voon Ong 1 , Thomas P Brady 1 , Jeffrey B Locke 1 , Shawn Flanagan 1 , Robert M Hughes 1 , Jeffrey L Stein 1 , Leslie W Tari 2
Affiliations
The ability of influenza virus to undergo rapid antigenic shift to elude humoral immunity highlights the need for effective broad-spectrum influenza antivirals for treatment, prophylaxis and pandemic preparedness. Strategies providing durable, universal influenza protection in healthy and high-risk populations are urgently needed. Here we describe the design and preclinical characterization of CD388, a first-in-class antiviral drug-Fc conjugate (DFC), in mice and cynomolgus macaques. CD388 comprises a multivalent conjugate of the influenza virus neuraminidase inhibitor zanamivir, linked to a CH1-Fc hybrid domain of human IgG1 engineered for extended half-life. CD388 improves the antiviral activity of zanamivir, demonstrating potent, universal activity across influenza A and B viruses, including high pathogenicity and neuraminidase inhibitor resistant strains, a low potential for resistance development and potent efficacy in lethal mouse infection models. These results suggest that CD388 has the potential for universal prevention of influenza A and B in healthy and high-risk populations.
. 2025 Mar 17.
doi: 10.1038/s41564-025-01955-3. Online ahead of print. Drug-Fc conjugate CD388 targets influenza virus neuraminidase and is broadly protective in mice
Simon Döhrmann # 1 , James Levin # 1 , Jason N Cole # 1 , Allen Borchardt # 1 , Karin Amundson 1 , Amanda Almaguer 1 , Elizabeth Abelovski 1 , Rajvir Grewal 1 , Douglas Zuill 1 , Nicholas Dedeic 1 , Grayson Hough 1 , Joanne Fortier 1 , Joanna Donatelli 1 , Thanh Lam 1 , Zhi-Yong Chen 1 , Wanlong Jiang 1 , Travis Haussener 1 , Alain Noncovich 1 , James M Balkovec 1 , Daniel C Bensen 1 , Voon Ong 1 , Thomas P Brady 1 , Jeffrey B Locke 1 , Shawn Flanagan 1 , Robert M Hughes 1 , Jeffrey L Stein 1 , Leslie W Tari 2
Affiliations
- PMID: 40097766
- DOI: 10.1038/s41564-025-01955-3
The ability of influenza virus to undergo rapid antigenic shift to elude humoral immunity highlights the need for effective broad-spectrum influenza antivirals for treatment, prophylaxis and pandemic preparedness. Strategies providing durable, universal influenza protection in healthy and high-risk populations are urgently needed. Here we describe the design and preclinical characterization of CD388, a first-in-class antiviral drug-Fc conjugate (DFC), in mice and cynomolgus macaques. CD388 comprises a multivalent conjugate of the influenza virus neuraminidase inhibitor zanamivir, linked to a CH1-Fc hybrid domain of human IgG1 engineered for extended half-life. CD388 improves the antiviral activity of zanamivir, demonstrating potent, universal activity across influenza A and B viruses, including high pathogenicity and neuraminidase inhibitor resistant strains, a low potential for resistance development and potent efficacy in lethal mouse infection models. These results suggest that CD388 has the potential for universal prevention of influenza A and B in healthy and high-risk populations.