A vaccine platform targeting lung-resident memory CD4+ T-cells provides protection against heterosubtypic influenza infections in mice and ferrets
Lung tissue-resident memory T (T<sub>RM</sub>) 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 T<sub>RM</sub> 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<sup>+</sup> T<sub>RM</sub> cells in the lungs in a type I interferon-dependent manner. These pulmonary CD4<sup>+</sup> T<sub>RM</sub> 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.
Authors
- Hyun Shik Bae
- Hyunsoo Park (ORCID: https://orcid.org/0000-0001-6924-1919)
- Jinsun Lee (ORCID: https://orcid.org/0000-0002-9345-724X)
- Seong‐Hyun Park (ORCID: https://orcid.org/0000-0002-0982-5338)
- Woonsung Na (ORCID: https://orcid.org/0000-0002-7254-5240)
- Seung Hyun Han (ORCID: https://orcid.org/0000-0001-9418-9278)
- Seung Bin (ORCID: https://orcid.org/0009-0004-7450-3791)
- Baik Lin Seong (ORCID: https://orcid.org/0000-0002-7301-082X)
- Dong-Ho Kim
- Jeong Woo Park (ORCID: https://orcid.org/0000-0002-8837-8045)
- Jun Heo (ORCID: https://orcid.org/0000-0002-7798-2909)
- Eunseo Bae
- Jaeseok Choi (ORCID: https://orcid.org/0009-0009-5381-0836)
- Somin Park (ORCID: https://orcid.org/0009-0001-0147-8183)
- Kwang-Wook Ko (ORCID: https://orcid.org/0009-0009-5734-596X)
Institutions
- Chonnam National University (KR)
- International Vaccine Institute (KR)
- Seoul National University (KR)
- Yonsei University (KR)
- Il-Yang Pharmaceutical (South Korea) (KR)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-11-29
- DOI
- https://doi.org/10.1038/s41467-024-54620-4
- Citations
- 17
- Primary Topic
- Influenza Virus Research Studies
- Type
- article
- Field-Weighted Citation Impact
- 6.57
Funders
- Chonnam National University
- Korea Health Industry Development Institute
- Korea Drug Development Fund
- Ministry of Science and ICT, South Korea