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<p>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.</p>

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Drug–Fc conjugate CD388 targets influenza virus neuraminidase and is broadly protective in mice

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年3月17日

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  • 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

摘要

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.