A humanized mouse model identifies key amino acids for low immunogenicity of H7N9 vaccines

Yamato Wada, Arnone Nithichanon, Eri Nobusawa, Leonard Moise, William D. Martin, Norio Yamamoto, Kazutaka Terahara, Haruhisa Hagiwara, Takato Odagiri, Masato Tashiro, Ganjana Lertmemongkolchai, Haruko Takeyama, Anne S.De Groot, Manabu Ato, Yoshimasa Takahashi

    Research output: Contribution to journalArticle

    12 Citations (Scopus)

    Abstract

    Influenza vaccines of H7N9 subtype are consistently less immunogenic in humans than vaccines developed for other subtypes. Although prior immunoinformatic analysis identified T-cell epitopes in H7 hemagglutinin (HA) which potentially enhance regulatory T cell response due to conservation with the human genome, the links between the T-cell epitopes and low immunogenicity of H7 HA remains unknown due to the lack of animal models reproducing the response observed in humans. Here, we utilized a humanized mouse model to recapitulate the low immunogenicity of H7 HA. Our analysis demonstrated that modification of a single H7 epitope by changing 3 amino acids so that it is homologous with a known H3 immunogenic epitope sequence significantly improved the immunogenicity of the H7 HA in the humanized mouse model, leading to a greater than 4-fold increase in HA-binding IgG responses. Thus, we provide experimental evidence for the important contribution of this H7-specific T cell epitope in determining the immunogenicity of an influenza vaccine. Furthermore, this study delineates strategies that can be used for screening and selecting vaccine strains using immunoinformatics tools and a humanized mouse model.

    Original languageEnglish
    Article number1283
    JournalScientific Reports
    Volume7
    Issue number1
    DOIs
    Publication statusPublished - 2017 Dec 1

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    T-Lymphocyte Epitopes
    Amino Acids
    Influenza Vaccines
    Epitopes
    Vaccines
    Hemagglutinins
    Human Genome
    Regulatory T-Lymphocytes
    Animal Models
    Immunoglobulin G
    avian influenza A virus hemagglutinin
    Vaccine Immunogenicity

    ASJC Scopus subject areas

    • General

    Cite this

    Wada, Y., Nithichanon, A., Nobusawa, E., Moise, L., Martin, W. D., Yamamoto, N., ... Takahashi, Y. (2017). A humanized mouse model identifies key amino acids for low immunogenicity of H7N9 vaccines. Scientific Reports, 7(1), [1283]. https://doi.org/10.1038/s41598-017-01372-5

    A humanized mouse model identifies key amino acids for low immunogenicity of H7N9 vaccines. / Wada, Yamato; Nithichanon, Arnone; Nobusawa, Eri; Moise, Leonard; Martin, William D.; Yamamoto, Norio; Terahara, Kazutaka; Hagiwara, Haruhisa; Odagiri, Takato; Tashiro, Masato; Lertmemongkolchai, Ganjana; Takeyama, Haruko; Groot, Anne S.De; Ato, Manabu; Takahashi, Yoshimasa.

    In: Scientific Reports, Vol. 7, No. 1, 1283, 01.12.2017.

    Research output: Contribution to journalArticle

    Wada, Y, Nithichanon, A, Nobusawa, E, Moise, L, Martin, WD, Yamamoto, N, Terahara, K, Hagiwara, H, Odagiri, T, Tashiro, M, Lertmemongkolchai, G, Takeyama, H, Groot, ASD, Ato, M & Takahashi, Y 2017, 'A humanized mouse model identifies key amino acids for low immunogenicity of H7N9 vaccines', Scientific Reports, vol. 7, no. 1, 1283. https://doi.org/10.1038/s41598-017-01372-5
    Wada Y, Nithichanon A, Nobusawa E, Moise L, Martin WD, Yamamoto N et al. A humanized mouse model identifies key amino acids for low immunogenicity of H7N9 vaccines. Scientific Reports. 2017 Dec 1;7(1). 1283. https://doi.org/10.1038/s41598-017-01372-5
    Wada, Yamato ; Nithichanon, Arnone ; Nobusawa, Eri ; Moise, Leonard ; Martin, William D. ; Yamamoto, Norio ; Terahara, Kazutaka ; Hagiwara, Haruhisa ; Odagiri, Takato ; Tashiro, Masato ; Lertmemongkolchai, Ganjana ; Takeyama, Haruko ; Groot, Anne S.De ; Ato, Manabu ; Takahashi, Yoshimasa. / A humanized mouse model identifies key amino acids for low immunogenicity of H7N9 vaccines. In: Scientific Reports. 2017 ; Vol. 7, No. 1.
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