A new article in Nature Scientific Reports (doi: 10.1038/s41598-017-01372-5) entitled A humanized mouse model identifies key amino acids for low immunogenicity of H7N9 vaccines may explain why H7N9 influenza vaccines are consistently less immunogenic in humans than vaccines developed for other subtypes of influenza.
In previous work, we identified a key T-cell epitope in H7 hemagglutinin (HA) that enhanced regulatory T cell response in human cells in vitro. We hypothesized that this was potentially due to conservation with the human genome (as discovered by our novel immunoinformatics tool, JanusMatrix.
In this newly published study, Wada, Takahashi, and Ato utilized a humanized mouse model to recapitulate the low immunogenicity of H7 HA. Furthermore, we 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 (also known as immune engineering 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.
This study provides the first experimental evidence for the important contribution of this H7-specific T cell epitope in determining the immunogenicity of an influenza vaccine. In addition, the publication illustrates a new approach to screening and selecting vaccine strains, using immunoinformatics tools and a humanized mouse model.