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Sci Rep. 2017 Apr 28;7(1):1283. doi: 10.1038/s41598-017-01372-5.
A humanized mouse model identifies key amino acids for low immunogenicity of H7N9 vaccines.
Wada Y1,2, Nithichanon A1,3, Nobusawa E4, Moise L5,6, Martin WD6, Yamamoto N4,7, Terahara K1, Hagiwara H8, Odagiri T4, Tashiro M4, Lertmemongkolchai G3, Takeyama H2, Groot AS5,6, Ato M1, Takahashi Y9.
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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.
PMID: 28455520 DOI: 10.1038/s41598-017-01372-5
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A humanized mouse model identifies key amino acids for low immunogenicity of H7N9 vaccines.
Wada Y1,2, Nithichanon A1,3, Nobusawa E4, Moise L5,6, Martin WD6, Yamamoto N4,7, Terahara K1, Hagiwara H8, Odagiri T4, Tashiro M4, Lertmemongkolchai G3, Takeyama H2, Groot AS5,6, Ato M1, Takahashi Y9.
Author information
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.
PMID: 28455520 DOI: 10.1038/s41598-017-01372-5
Free full text