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

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 Liu, Laurence J. N. Cooper, Courtney M. Sands, Vallabh E. Das, Manu Sebastian, Brett L. Hurst and Navin Varadarajan ()
Additional contact information
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

Nature Communications, 2024, vol. 15, issue 1, 1-21

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-50234-y

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