Multi-antigen intranasal vaccine protects against challenge with sarbecoviruses and prevents transmission in hamsters

Ankita Leekha, Arash Saeedi, K M Samiur Rahman Sefat, Monish Kumar, Melisa Martinez-Paniagua, Adrian Damian, Rohan Kulkarni, Kate Reichel, Ali Rezvan, Shalaleh Masoumi, Xinli Liu, Laurence J. N. Cooper, Manu Sebastian, Courtney M. Sands, Vallabh E. Das, Nimesh B. Patel, Brett Hurst and Navin Varadarajan ()
Additional contact information
Ankita Leekha: University of Houston
Arash Saeedi: University of Houston
K M Samiur Rahman Sefat: University of Houston
Monish Kumar: University of Houston
Melisa Martinez-Paniagua: University of Houston
Adrian Damian: University of Houston
Rohan Kulkarni: University of Houston
Kate Reichel: University of Houston
Ali Rezvan: University of Houston
Shalaleh Masoumi: University of Houston
Xinli Liu: University of Houston
Laurence J. N. Cooper: AuraVax Therapeutics
Manu Sebastian: AuraVax Therapeutics
Courtney M. Sands: University of Houston
Vallabh E. Das: University of Houston
Nimesh B. Patel: University of Houston
Brett Hurst: Utah State University
Navin Varadarajan: University of Houston

Nature Communications, 2024, vol. 15, issue 1, 1-20

Abstract: Abstract Immunization programs against SARS-CoV-2 with commercial intramuscular vaccines prevent disease but are less efficient in preventing infections. Mucosal vaccines can provide improved protection against transmission, ideally for different variants of concern (VOCs) and related sarbecoviruses. Here, we report a multi-antigen, intranasal vaccine, NanoSTING-SN (NanoSTING-Spike-Nucleocapsid), eliminates virus replication in both the lungs and the nostrils upon challenge with the pathogenic SARS-CoV-2 Delta VOC. We further demonstrate that NanoSTING-SN prevents transmission of the SARS-CoV-2 Omicron VOC (BA.5) to vaccine-naïve hamsters. To evaluate protection against other sarbecoviruses, we immunized mice with NanoSTING-SN. We showed that immunization affords protection against SARS-CoV, leading to protection from weight loss and 100% survival in mice. In non-human primates, animals immunized with NanoSTING-SN show durable serum IgG responses (6 months) and nasal wash IgA responses cross-reactive to SARS-CoV-2 (XBB1.5), SARS-CoV and MERS-CoV antigens. These observations have two implications: (1) mucosal multi-antigen vaccines present a pathway to reducing transmission of respiratory viruses, and (2) eliciting immunity against multiple antigens can be advantageous in engineering pan-sarbecovirus vaccines.

Date: 2024
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DOI: 10.1038/s41467-024-50133-2

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