Drug–Fc conjugate CD388 targets influenza virus neuraminidase and is broadly protective in mice
Year: 2025
Type: article
Abstract: 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. CD388 is a first-in-class antiviral drug–Fc conjugate engineered for extended half-life that demonstrates potent prophylactic and therapeutic efficacy against lethal influenza A and B challenge in mice.
Source: Nature Microbiology
Authors: Simon Döhrmann, James Levin, Jason N. Cole, Allen Borchardt, Karin Amundson, Amanda Almaguer, Elizabeth Abelovski, Rajvir Grewal, Douglas Zuill, Nicholas Dedeic, Grayson Hough, Joanne Fortier, Joanna Donatelli, Thanh Lam, Zhi-Yong Chen, Wanlong Jiang, Travis Haussener, Alain Noncovich, James M. Balkovec, Daniel C. Bensen, Voon Ong, Thomas P. Brady, Jeffrey B. Locke, Shawn Flanagan, Robert M. Hughes, Jeffrey L. Stein, Leslie W. Tari
Institution: Cidara Therapeutics (United States)
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $12,690
Funder: Cidara Therapeutics
OpenAlex ID: W4408502000