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

Author

Listed:
  • Kwang Hyun Ko

    (NA Vaccine Institute
    Seoul National University)

  • Hyun Shik Bae

    (NA Vaccine Institute)

  • Jeong Woo Park

    (Seoul National University
    Seoul National University)

  • Jin-Sun Lee

    (Seoul National University
    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
    Seoul National University)

  • Dong-Ho Kim

    (NA Vaccine Institute)

  • Seung Bin Cha

    (NA Vaccine Institute)

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.

Suggested Citation

  • 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-, 2024. "A vaccine platform targeting lung-resident memory CD4+ T-cells provides protection against heterosubtypic influenza infections in mice and ferrets," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-54620-4
    DOI: 10.1038/s41467-024-54620-4
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    References listed on IDEAS

    as
    1. Haina Shin & Akiko Iwasaki, 2012. "A vaccine strategy that protects against genital herpes by establishing local memory T cells," Nature, Nature, vol. 491(7424), pages 463-467, November.
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    3. Jenna J. Guthmiller & Julianna Han & Henry A. Utset & Lei Li & Linda Yu-Ling Lan & Carole Henry & Christopher T. Stamper & Meagan McMahon & George O’Dell & Monica L. Fernández-Quintero & Alec W. Freyn, 2022. "Broadly neutralizing antibodies target a haemagglutinin anchor epitope," Nature, Nature, vol. 602(7896), pages 314-320, February.
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