Citation: Xiantao Zhang, Yingtong Lin, Jie Liu, Dongming Wang, Jiayi Yuan, Ran Chen, Xu Zhang, Xue Zhang, Nan Zhou, Hui Zhang, Xin He. Ferritin nanoparticle-based vaccine enhances mucosal immunity by promoting antigen uptake and activation of alveolar macrophages .VIROLOGICA SINICA, 2026, 41(5) : 1251-1255.  http://dx.doi.org/10.1016/j.virs.2026.08.004

Ferritin nanoparticle-based vaccine enhances mucosal immunity by promoting antigen uptake and activation of alveolar macrophages

  • Highlights
    1 Ferritin nanoparticle-displayed mosaic tandem-RBD enhances respiratory mucosal immunity.
    2 Intranasal immunization induces broad neutralizing antibodies and tissue-resident immune populations.
    3 Nanoparticles promote antigen processing and presentation programs in alveolar macrophages.

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  • 10.1016j.virs.2026.08.004-ESM2.xlsx
    10.1016j.virs.2026.08.004-ESM1.docx
    1. Aegerter, H., Kulikauskaite, J., Crotta, S., Patel, H., Kelly, G., Hessel, E.M., Mack, M., Beinke, S., Wack, A., 2020. Influenza-induced monocyte-derived alveolar macrophages confer prolonged antibacterial protection. Nat Immunol 21, 145-157.

    2. Chen, S., Zhang, X., Yao, Y., Wang, S., Li, K., Zhang, B., Ye, T., Chen, L., Wu, Y., Li, E., Xu, B., Zhang, P., Chuai, X., Ran, Y., Gong, R., Zhang, H., Chiu, S., 2024. Ferritin nanoparticle-based Nipah virus glycoprotein vaccines elicit potent protective immune responses in mice and hamsters. Virol Sin 39, 909-916.

    3. Cohen, A.A., van Doremalen, N., Greaney, A.J., Andersen, H., Sharma, A., Starr, T.N., Keeffe, J.R., Fan, C., Schulz, J.E., Gnanapragasam, P.N.P., Kakutani, L.M., West, A.P., Jr., Saturday, G., Lee, Y.E., Gao, H., Jette, C.A., Lewis, M.G., Tan, T.K., Townsend, A.R., Bloom, J.D., Munster, V.J., Bjorkman, P.J., 2022. Mosaic RBD nanoparticles protect against challenge by diverse sarbecoviruses in animal models. Science 377, eabq0839.

    4. Eshaghi, B., Schudel, A., Sadeghi, I., Chen, Z., Lee, A.H., Kanelli, M., Tierney, F., Han, J., Ingalls, B., Francis, D.M., Li, G., von Andrian, U., Langer, R., Jaklenec, A., 2024. The role of engineered materials in mucosal vaccination strategies. Nature Reviews Materials 9, 29-45.

    5. Hussell, T., Bell, T.J., 2014. Alveolar macrophages: plasticity in a tissue-specific context. Nat Rev Immunol 14, 81-93.

    6. Kawasaki, T., Ikegawa, M., Yunoki, K., Otani, H., Ori, D., Ishii, K.J., Kuroda, E., Takamura, S., Kitabatake, M., Ito, T., Isotani, A., Kawai, T., 2022. Alveolar macrophages instruct CD8(+) T cell expansion by antigen cross-presentation in lung. Cell Rep 41, 111828.

    7. Kiyono, H., Ernst, P.B., 2025. Nasal vaccines for respiratory infections. Nature 641, 321-330.

    8. Ma, X., Zou, F., Yu, F., Li, R., Yuan, Y., Zhang, Y., Zhang, X., Deng, J., Chen, T., Song, Z., Qiao, Y., Zhan, Y., Liu, J., Zhang, J., Zhang, X., Peng, Z., Li, Y., Lin, Y., Liang, L., Wang, G., Chen, Y., Chen, Q., Pan, T., He, X., Zhang, H., 2020. Nanoparticle Vaccines Based on the Receptor Binding Domain (RBD) and Heptad Repeat (HR) of SARS-CoV-2 Elicit Robust Protective Immune Responses. Immunity 53, 1315-1330 e1319.

    9. Malainou, C., Abdin, S.M., Lachmann, N., Matt, U., Herold, S., 2023. Alveolar macrophages in tissue homeostasis, inflammation, and infection: evolving concepts of therapeutic targeting. J Clin Invest 133.

    10. Mettelman, R.C., Allen, E.K., Thomas, P.G., 2022. Mucosal immune responses to infection and vaccination in the respiratory tract. Immunity 55, 749-780.

    11. Zhang, X., Wu, S., Liu, J., Chen, R., Zhang, Y., Lin, Y., Xi, Z., Deng, J., Pu, Z., Liang, C., Feng, J., Li, R., Lin, K., Zhou, M., Liu, Y., Zhang, X., Liu, B., Zhang, Y., He, X., Zhang, H., 2023. A Mosaic Nanoparticle Vaccine Elicits Potent Mucosal Immune Response with Significant Cross-Protection Activity against Multiple SARS-CoV-2 Sublineages. Adv Sci (Weinh) 10, e2301034.

    12. Zhang, X., Yuan, Y., Wu, B., Wang, X., Lin, Y., Luo, Y., Li, R., Chen, T., Deng, J., Zhang, X., Zou, F., He, X., Zhang, H., 2021. Improvement of a SARS-CoV-2 vaccine by enhancing the conjugation efficiency of the immunogen to self-assembled nanoparticles. Cell Mol Immunol 18, 2042-2044.

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    Ferritin nanoparticle-based vaccine enhances mucosal immunity by promoting antigen uptake and activation of alveolar macrophages

      Corresponding author: Xue Zhang, zhangxuea@gdpu.edu.cn
      Corresponding author: Nan Zhou, zhoun55@mail.sysu.edu.cn
      Corresponding author: Hui Zhang, zhangh92@mail.sysu.edu.cn
      Corresponding author: Xin He, hexin59@mail.sysu.edu.cn
    • a. Institute of Human Virology, Department of Pathogen Biology and Biosecurity, Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China;
    • b. The Second Clinical Medical School of Guangdong Pharmaceutical University (Guangdong Second Provincial General Hospital), Guangzhou 510317, China;
    • c. Center for Infection and Immunity Study, Zhongshan School of Medicine, Sun Yat-sen University, Shenzhen 518107, China

    Abstract: Highlights
    1 Ferritin nanoparticle-displayed mosaic tandem-RBD enhances respiratory mucosal immunity.
    2 Intranasal immunization induces broad neutralizing antibodies and tissue-resident immune populations.
    3 Nanoparticles promote antigen processing and presentation programs in alveolar macrophages.

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