tetano
Editor, Senior Moderator
Sci Rep. 2017 Apr 28;7(1):1283. doi: 10.1038/s41598-017-01372-5.
[h=1]A humanized mouse model identifies key amino acids for low immunogenicity of H7N9 vaccines.[/h] Wada Y[SUP]1,[/SUP][SUP]2[/SUP], Nithichanon A[SUP]1,[/SUP][SUP]3[/SUP], Nobusawa E[SUP]4[/SUP], Moise L[SUP]5,[/SUP][SUP]6[/SUP], Martin WD[SUP]6[/SUP], Yamamoto N[SUP]4,[/SUP][SUP]7[/SUP], Terahara K[SUP]1[/SUP], Hagiwara H[SUP]8[/SUP], Odagiri T[SUP]4[/SUP], Tashiro M[SUP]4[/SUP], Lertmemongkolchai G[SUP]3[/SUP], Takeyama H[SUP]2[/SUP], Groot AS[SUP]5,[/SUP][SUP]6[/SUP], Ato M[SUP]1[/SUP], Takahashi Y[SUP]9[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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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[h=1]A humanized mouse model identifies key amino acids for low immunogenicity of H7N9 vaccines.[/h] Wada Y[SUP]1,[/SUP][SUP]2[/SUP], Nithichanon A[SUP]1,[/SUP][SUP]3[/SUP], Nobusawa E[SUP]4[/SUP], Moise L[SUP]5,[/SUP][SUP]6[/SUP], Martin WD[SUP]6[/SUP], Yamamoto N[SUP]4,[/SUP][SUP]7[/SUP], Terahara K[SUP]1[/SUP], Hagiwara H[SUP]8[/SUP], Odagiri T[SUP]4[/SUP], Tashiro M[SUP]4[/SUP], Lertmemongkolchai G[SUP]3[/SUP], Takeyama H[SUP]2[/SUP], Groot AS[SUP]5,[/SUP][SUP]6[/SUP], Ato M[SUP]1[/SUP], Takahashi Y[SUP]9[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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