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

• Published in: Scientific reports Vol. 7; no. 1; pp. 1283 - 11
• Main Authors: 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, De Groot, Anne S., Ato, Manabu, Takahashi, Yoshimasa
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 28.04.2017; Nature Publishing Group; Nature Portfolio
• Subjects: 13/1; 631/250/255/2514; 631/250/590/2294; 64/60; 82/80; Amino acids; Amino Acids - genetics; Amino Acids - immunology; Animal models; Animals; Antibodies, Viral - immunology; Disease Models, Animal; Epitopes; Epitopes, T-Lymphocyte - genetics; Epitopes, T-Lymphocyte - immunology; Genomes; Hemagglutinins; Humanities and Social Sciences; Humans; Immunogenicity; Immunogenicity, Vaccine; Immunoglobulin G; Influenza; Influenza A Virus, H3N2 Subtype - immunology; Influenza A Virus, H7N9 Subtype - immunology; Influenza Vaccines - immunology; Influenza, Human - immunology; Lymphocytes T; Mice, Inbred BALB C; multidisciplinary; Mutation; Science; Science (multidisciplinary); Vaccines
• DOI: 10.1038/s41598-017-01372-5
• ISSN: 2045-2322

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.