A vaccine platform targeting lung-resident memory CD4+ T-cells provides protection against heterosubtypic influenza infections in mice and ferrets

Kwang Hyun Ko, Hyun Shik Bae, Jeong Woo Park, Jin-Sun Lee, Somin Park, Jun Heo, Hyunsoo Park, Jaeseok Choi, Eunseo Bae, Woonsung Na, Seong-Hyun Park, Baik-Lin Seong, Seung Hyun Han, Dong-Ho Kim () and Seung Bin Cha ()
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Kwang Hyun Ko: NA Vaccine Institute
Hyun Shik Bae: NA Vaccine Institute
Jeong Woo Park: Seoul National University
Jin-Sun Lee: Seoul National University
Somin Park: Seoul National University
Jun Heo: Il-Yang Pharmaceutical
Hyunsoo Park: Il-Yang Pharmaceutical
Jaeseok Choi: Chonnam National University
Eunseo Bae: Chonnam National University
Woonsung Na: Chonnam National University
Seong-Hyun Park: Yonsei University
Baik-Lin Seong: Seodaemun-gu
Seung Hyun Han: Seoul National University
Dong-Ho Kim: NA Vaccine Institute
Seung Bin Cha: NA Vaccine Institute

Nature Communications, 2024, vol. 15, issue 1, 1-19

Abstract: Abstract Lung tissue-resident memory T (TRM) cells induced by influenza vaccination are crucial for heterosubtypic immunity upon re-exposure to the influenza virus, enabling rapid and robust responses upon reactivation. To enhance the efficacy of influenza vaccines, we induce the generation of lung TRM cells following intranasal vaccination with a commercial influenza vaccine adjuvanted with NexaVant (NVT), a TLR3 agonist-based adjuvant. We demonstrate that intranasal immunization with the NVT-adjuvanted vaccine provides improved protection against influenza virus infections by inducing the generation of CD4+ TRM cells in the lungs in a type I interferon-dependent manner. These pulmonary CD4+ TRM cells provide potent mucosal immunity and cross-protection against heterosubtypic infections in both mouse and ferret models. This vaccine platform has the potential to significantly improve conventional intramuscular influenza vaccines by providing broader protection.

Date: 2024
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DOI: 10.1038/s41467-024-54620-4

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