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An intranasal nanoparticle STING agonist protects against respiratory viruses in animal models

Author

Listed:
  • Ankita Leekha

    (University of Houston)

  • Arash Saeedi

    (University of Houston)

  • Monish Kumar

    (University of Houston)

  • K. M. Samiur Rahman Sefat

    (University of Houston)

  • Melisa Martinez-Paniagua

    (University of Houston)

  • Hui Meng

    (University of Houston)

  • Mohsen Fathi

    (University of Houston)

  • Rohan Kulkarni

    (University of Houston)

  • Kate Reichel

    (University of Houston)

  • Sujit Biswas

    (University of Houston)

  • Daphne Tsitoura

    (AuraVax Therapeutics)

  • Xinli Liu

    (University of Houston)

  • Laurence J. N. Cooper

    (AuraVax Therapeutics)

  • Courtney M. Sands

    (University of Houston)

  • Vallabh E. Das

    (University of Houston)

  • Manu Sebastian

    (AuraVax Therapeutics)

  • Brett L. Hurst

    (Utah State University)

  • Navin Varadarajan

    (University of Houston)

Abstract

Respiratory viral infections cause morbidity and mortality worldwide. Despite the success of vaccines, vaccination efficacy is weakened by the rapid emergence of viral variants with immunoevasive properties. The development of an off-the-shelf, effective, and safe therapy against respiratory viral infections is thus desirable. Here, we develop NanoSTING, a nanoparticle formulation of the endogenous STING agonist, 2′−3′ cGAMP, to function as an immune activator and demonstrate its safety in mice and rats. A single intranasal dose of NanoSTING protects against pathogenic strains of SARS-CoV-2 (alpha and delta VOC) in hamsters. In transmission experiments, NanoSTING reduces the transmission of SARS-CoV-2 Omicron VOC to naïve hamsters. NanoSTING also protects against oseltamivir-sensitive and oseltamivir-resistant strains of influenza in mice. Mechanistically, NanoSTING upregulates locoregional interferon-dependent and interferon-independent pathways in mice, hamsters, as well as non-human primates. Our results thus implicate NanoSTING as a broad-spectrum immune activator for controlling respiratory virus infection.

Suggested Citation

  • Ankita Leekha & Arash Saeedi & Monish Kumar & K. M. Samiur Rahman Sefat & Melisa Martinez-Paniagua & Hui Meng & Mohsen Fathi & Rohan Kulkarni & Kate Reichel & Sujit Biswas & Daphne Tsitoura & Xinli Li, 2024. "An intranasal nanoparticle STING agonist protects against respiratory viruses in animal models," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50234-y
    DOI: 10.1038/s41467-024-50234-y
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