tetano
Editor, Senior Moderator
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[SUP] #[/SUP][SUP] 1 [/SUP], James Levin[SUP] #[/SUP][SUP] 1 [/SUP], Jason N Cole[SUP] #[/SUP][SUP] 1 [/SUP], Allen Borchardt[SUP] #[/SUP][SUP] 1 [/SUP], Karin Amundson[SUP] 1 [/SUP], Amanda Almaguer[SUP] 1 [/SUP], Elizabeth Abelovski[SUP] 1 [/SUP], Rajvir Grewal[SUP] 1 [/SUP], Douglas Zuill[SUP] 1 [/SUP], Nicholas Dedeic[SUP] 1 [/SUP], Grayson Hough[SUP] 1 [/SUP], Joanne Fortier[SUP] 1 [/SUP], Joanna Donatelli[SUP] 1 [/SUP], Thanh Lam[SUP] 1 [/SUP], Zhi-Yong Chen[SUP] 1 [/SUP], Wanlong Jiang[SUP] 1 [/SUP], Travis Haussener[SUP] 1 [/SUP], Alain Noncovich[SUP] 1 [/SUP], James M Balkovec[SUP] 1 [/SUP], Daniel C Bensen[SUP] 1 [/SUP], Voon Ong[SUP] 1 [/SUP], Thomas P Brady[SUP] 1 [/SUP], Jeffrey B Locke[SUP] 1 [/SUP], Shawn Flanagan[SUP] 1 [/SUP], Robert M Hughes[SUP] 1 [/SUP], Jeffrey L Stein[SUP] 1 [/SUP], Leslie W Tari[SUP] 2 [/SUP]
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[SUP] #[/SUP][SUP] 1 [/SUP], James Levin[SUP] #[/SUP][SUP] 1 [/SUP], Jason N Cole[SUP] #[/SUP][SUP] 1 [/SUP], Allen Borchardt[SUP] #[/SUP][SUP] 1 [/SUP], Karin Amundson[SUP] 1 [/SUP], Amanda Almaguer[SUP] 1 [/SUP], Elizabeth Abelovski[SUP] 1 [/SUP], Rajvir Grewal[SUP] 1 [/SUP], Douglas Zuill[SUP] 1 [/SUP], Nicholas Dedeic[SUP] 1 [/SUP], Grayson Hough[SUP] 1 [/SUP], Joanne Fortier[SUP] 1 [/SUP], Joanna Donatelli[SUP] 1 [/SUP], Thanh Lam[SUP] 1 [/SUP], Zhi-Yong Chen[SUP] 1 [/SUP], Wanlong Jiang[SUP] 1 [/SUP], Travis Haussener[SUP] 1 [/SUP], Alain Noncovich[SUP] 1 [/SUP], James M Balkovec[SUP] 1 [/SUP], Daniel C Bensen[SUP] 1 [/SUP], Voon Ong[SUP] 1 [/SUP], Thomas P Brady[SUP] 1 [/SUP], Jeffrey B Locke[SUP] 1 [/SUP], Shawn Flanagan[SUP] 1 [/SUP], Robert M Hughes[SUP] 1 [/SUP], Jeffrey L Stein[SUP] 1 [/SUP], Leslie W Tari[SUP] 2 [/SUP]
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.