RIKEN IMS AnnualReport 2020

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TFHPandemic infection with the new coronavirus (SARS-CoV-2) that causes 37TH1B cellB cellLive virus infectionVaccinationStrain-specific epitopesExpose common epitopesVirus replicationInactivated virusStrain-specific epitopesCommon epitopesrespiratory diseases is a very serious public health problem. Influenza vi-ruses are also known to be the causative pathogen of a severe acute respiratory infection. Vaccines are widely accepted as the most effective protective measure against respiratory virus infection. We and others found that the immune re-sponses induced with currently available inactivated vaccines were very differ-ent from the immune responses induced by a natural viral infection. In a recent publication in Trends in Immunology, we discuss the germinal center (GC) dependency of the responses and the breadth of antibody responses between vaccines and infection (Figure) (Kubo M et al. 2020 Trends in Immunology).Inactivated vaccines induce effective neutralizing antibodies against the emerged influenza virus, but the response is narrow and limited to the vac-cine virus strain. Meanwhile, natural viral infection induces a potentially wider breadth of antibody responses, which can protect against heterotypic virus infection. The broadly neutralizing antibody (bnAb) responses in the natural infection largely depends on TFH cell-dependent GC responses, because the lack of Bcl-6 expression in T or B cells diminishes the production of bnAbs. On the other hand, the neutralizing antibodies induced by the inactivated vaccines are independent of the GC response. We discuss recent advances concerning the contribution of TFH cells and GC responses to the generation of bnAbs that recognize common epitopes shared by heterotypic influenza viruses. This in-formation may shed light on strategies for the development of a universal vac-cine capable of establishing protection beyond the barrier of virus mutation and strain differences.Figure: The breadth of antibody responses in-duced by influenza vaccination and infectionVaccination with inactivated viruses induces rapid but narrow IgG responses against influenza HA through TH1 cell-dependent B cell activation. On the other hand, natural viral infection induces broadly reactive IgG re-sponses through TFH cell-dependent GC B cell activation.Recent Major PublicationsWang F, Trier AM, Li F, Kim S, Chen Z, Chai JN, Mack MR, Morrison SA, Hamilton JD, Baek J, Yang TB, Ver Heul AM, Xie AZ, Dong X, Kubo M, Hu H, Hsieh CS, Dong X, Liu Q, Margolis DJ, Ardeleanu M, Miller MJ, Kim BS. A basophil-neuronal axis promotes itch. Cell 184, 422-440.e17 (2021)Kubo M. Diurnal Rhythmicity Programs of Microbiota and Transcriptional Oscillation of Circadian Regulator, NFIL3. Front Immunol 11, 552188 (2020)Kubo M, Miyauchi K. Breadth of Antibody Responses during Influenza Virus Infection and Vaccination. Trends Immunol 41, 394-405 (2020)Invited presentationsKubo M. “Role of IL4/IL13 in the pathogenesis of atopic dermatitis” The 50th Annual Meeting of the Japanese Society for Cutaneous Immunology and Allergy (Kochi, Japan/Online) December 2020Kubo M. “IL-4 and IL-13–their roles in Type 2 inflamma-tion in allergic diseases” 1st Anniversary Commemora-tive Lecture of Dupixent Launch (Tokyo, Japan/Online) September 2020Kubo M. “The Role of Type 2 Cytokines in Allergic Inflam-mation” Science Exchange Meeting in Kagoshima 2020 (Kagoshima, Japan/Online) June 2020Kubo M. “Skin homeostasis and atopic dermatitis” 7th International Postgraduate Conference on Pharma-ceutical Sciences (iPoPS2020) (Noda, Japan) February 2020Kubo M. “The Role of Type 2 Cytokines in Allergic Inflam-mation” Sanofi lecture series on Severe Asthma (Tokyo, Japan) February 2020IFN-IL-21IL-4Laboratory for Cytokine RegulationTeam Leader: Masato Kubo