A humanized mouse model identifies key amino acids for low immunogenicity of H7N9 vaccines
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 wi...
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Nature Portfolio
2017
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oai:doaj.org-article:592d0fec53c8484cb924caf5ee6528562021-12-02T12:32:33ZA humanized mouse model identifies key amino acids for low immunogenicity of H7N9 vaccines10.1038/s41598-017-01372-52045-2322https://doaj.org/article/592d0fec53c8484cb924caf5ee6528562017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01372-5https://doaj.org/toc/2045-2322Abstract 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.Yamato WadaArnone NithichanonEri NobusawaLeonard MoiseWilliam D. MartinNorio YamamotoKazutaka TeraharaHaruhisa HagiwaraTakato OdagiriMasato TashiroGanjana LertmemongkolchaiHaruko TakeyamaAnne S. De GrootManabu AtoYoshimasa TakahashiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017) |
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Medicine R Science Q 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 A humanized mouse model identifies key amino acids for low immunogenicity of H7N9 vaccines |
| description |
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. |
| format |
article |
| author |
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 |
| author_facet |
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 |
| author_sort |
Yamato Wada |
| title |
A humanized mouse model identifies key amino acids for low immunogenicity of H7N9 vaccines |
| title_short |
A humanized mouse model identifies key amino acids for low immunogenicity of H7N9 vaccines |
| title_full |
A humanized mouse model identifies key amino acids for low immunogenicity of H7N9 vaccines |
| title_fullStr |
A humanized mouse model identifies key amino acids for low immunogenicity of H7N9 vaccines |
| title_full_unstemmed |
A humanized mouse model identifies key amino acids for low immunogenicity of H7N9 vaccines |
| title_sort |
humanized mouse model identifies key amino acids for low immunogenicity of h7n9 vaccines |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/592d0fec53c8484cb924caf5ee652856 |
| work_keys_str_mv |
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