tetano
Editor, Senior Moderator
Nat Commun. 2019 Aug 28;10(1):3883. doi: 10.1038/s41467-019-11821-6.
[h=1]Exposure of an occluded hemagglutinin epitope drives selection of a class of cross-protective influenza antibodies.[/h] Adachi Y[SUP]1[/SUP], Tonouchi K[SUP]1,[/SUP][SUP]2[/SUP], Nithichanon A[SUP]1,[/SUP][SUP]3[/SUP], Kuraoka M[SUP]4[/SUP], Watanabe A[SUP]4[/SUP], Shinnakasu R[SUP]5[/SUP], Asanuma H[SUP]6,[/SUP][SUP]7[/SUP], Ainai A[SUP]7[/SUP], Ohmi Y[SUP]8[/SUP], Yamamoto T[SUP]9[/SUP], Ishii KJ[SUP]10,[/SUP][SUP]11[/SUP], Hasegawa H[SUP]6,[/SUP][SUP]7[/SUP], Takeyama H[SUP]2[/SUP], Lertmemongkolchai G[SUP]3[/SUP], Kurosaki T[SUP]5,[/SUP][SUP]12[/SUP], Ato M[SUP]13[/SUP], Kelsoe G[SUP]4,[/SUP][SUP]14[/SUP], Takahashi Y[SUP]15[/SUP].
[h=3]Author information[/h] 1 Department of Immunology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku, Tokyo, 162-8640, Japan. 2 Department of Life Science and Medical Bioscience, Waseda University, 2-2 Wakamatsucho, Shinjuku, Tokyo, 162-8480, Japan. 3 Center for Research and Development of Medical Diagnostic Laboratories (CMDL), Faculty of Associated Medical Sciences, Khon Kaen University, 123 Mittraphap Road, Khon Kaen, 40002, Thailand. 4 Department of Immunology, Duke University, Durham, NC, 27710, USA. 5 Laboratory of Lymphocyte Differentiation, WPI Immunology Frontier Research Center and Graduate School of Frontier Biosciences, Osaka University, 3-1 Yamadaoka, Suita, Osaka, 565-0871, Japan. 6 Influenza Virus Research Center, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama, Tokyo, 208-0011, Japan. 7 Department of Pathology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku, Tokyo, 162-8640, Japan. 8 Department of Clinical Engineering, Chubu University College of Life and Health Sciences, 1200 Matsumoto, Kasugai, 487-8501, Aichi, Japan. 9 Laboratory of Immunosenescence, Center for Vaccine and Adjuvant Research, National Institutes of Biomedical Innovation, Health and Nutrition, 7-6-8 Saitoasagi, Ibaraki, Osaka, 567-0085, Japan. 10 Center for Vaccine and Adjuvant Research, National Institutes of Biomedical Innovation, Health and Nutrition, 7-6-8 Saitoasagi, Ibaraki, Osaka, 567-0085, Japan. 11 Division of Vaccine Science, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shiroganedai, Minato, Tokyo, 108-8639, Japan. 12 Laboratory for Lymphocyte Differentiation, RIKEN Center for Integrative Medical Sciences, 1-7-22 Suehirocho, Tsurumi, Yokohama, Kanagawa, 230-0045, Japan. 13 Department of Mycobacteriology, National Institute of Infectious Diseases, 4-2-1 Aobacho, Higashimurayama, Tokyo, 189-0002, Japan. 14 Human Vaccine Institute, Duke University, Durham, NC, 27710, USA. 15 Department of Immunology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku, Tokyo, 162-8640, Japan. ytakahas@niid.go.jp.
[h=3]Abstract[/h] Germinal center (GC) B cells at viral replication sites acquire specificity to poorly immunogenic but conserved influenza hemagglutinin (HA) epitopes. Here, high-throughput epitope mapping of local GC B cells is used to identify conserved HA epitope selecting cross-reactive antibodies that mediate heterosubtypic protection. A distinct feature of this epitope is an occlusion in the naive trimeric HA structure that is exposed in the post-fusion HA structure to occur under low pH conditions during viral replication. Importantly, systemic immunization by the post-fusion HA antigen results in GC B cells targeting the occluded epitope, and induces a class of protective antibodies that have cross-group specificity and afford protection independent of virus neutralization activity. Furthermore, this class of broadly protective antibodies develops at late time points and persists. Our results identify a class of cross-protective antibodies that are selected at the viral replication site, and provide insights into vaccine strategies using the occluded epitope.
PMID: 31462639 DOI: 10.1038/s41467-019-11821-6
[h=1]Exposure of an occluded hemagglutinin epitope drives selection of a class of cross-protective influenza antibodies.[/h] Adachi Y[SUP]1[/SUP], Tonouchi K[SUP]1,[/SUP][SUP]2[/SUP], Nithichanon A[SUP]1,[/SUP][SUP]3[/SUP], Kuraoka M[SUP]4[/SUP], Watanabe A[SUP]4[/SUP], Shinnakasu R[SUP]5[/SUP], Asanuma H[SUP]6,[/SUP][SUP]7[/SUP], Ainai A[SUP]7[/SUP], Ohmi Y[SUP]8[/SUP], Yamamoto T[SUP]9[/SUP], Ishii KJ[SUP]10,[/SUP][SUP]11[/SUP], Hasegawa H[SUP]6,[/SUP][SUP]7[/SUP], Takeyama H[SUP]2[/SUP], Lertmemongkolchai G[SUP]3[/SUP], Kurosaki T[SUP]5,[/SUP][SUP]12[/SUP], Ato M[SUP]13[/SUP], Kelsoe G[SUP]4,[/SUP][SUP]14[/SUP], Takahashi Y[SUP]15[/SUP].
[h=3]Author information[/h] 1 Department of Immunology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku, Tokyo, 162-8640, Japan. 2 Department of Life Science and Medical Bioscience, Waseda University, 2-2 Wakamatsucho, Shinjuku, Tokyo, 162-8480, Japan. 3 Center for Research and Development of Medical Diagnostic Laboratories (CMDL), Faculty of Associated Medical Sciences, Khon Kaen University, 123 Mittraphap Road, Khon Kaen, 40002, Thailand. 4 Department of Immunology, Duke University, Durham, NC, 27710, USA. 5 Laboratory of Lymphocyte Differentiation, WPI Immunology Frontier Research Center and Graduate School of Frontier Biosciences, Osaka University, 3-1 Yamadaoka, Suita, Osaka, 565-0871, Japan. 6 Influenza Virus Research Center, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama, Tokyo, 208-0011, Japan. 7 Department of Pathology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku, Tokyo, 162-8640, Japan. 8 Department of Clinical Engineering, Chubu University College of Life and Health Sciences, 1200 Matsumoto, Kasugai, 487-8501, Aichi, Japan. 9 Laboratory of Immunosenescence, Center for Vaccine and Adjuvant Research, National Institutes of Biomedical Innovation, Health and Nutrition, 7-6-8 Saitoasagi, Ibaraki, Osaka, 567-0085, Japan. 10 Center for Vaccine and Adjuvant Research, National Institutes of Biomedical Innovation, Health and Nutrition, 7-6-8 Saitoasagi, Ibaraki, Osaka, 567-0085, Japan. 11 Division of Vaccine Science, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shiroganedai, Minato, Tokyo, 108-8639, Japan. 12 Laboratory for Lymphocyte Differentiation, RIKEN Center for Integrative Medical Sciences, 1-7-22 Suehirocho, Tsurumi, Yokohama, Kanagawa, 230-0045, Japan. 13 Department of Mycobacteriology, National Institute of Infectious Diseases, 4-2-1 Aobacho, Higashimurayama, Tokyo, 189-0002, Japan. 14 Human Vaccine Institute, Duke University, Durham, NC, 27710, USA. 15 Department of Immunology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku, Tokyo, 162-8640, Japan. ytakahas@niid.go.jp.
[h=3]Abstract[/h] Germinal center (GC) B cells at viral replication sites acquire specificity to poorly immunogenic but conserved influenza hemagglutinin (HA) epitopes. Here, high-throughput epitope mapping of local GC B cells is used to identify conserved HA epitope selecting cross-reactive antibodies that mediate heterosubtypic protection. A distinct feature of this epitope is an occlusion in the naive trimeric HA structure that is exposed in the post-fusion HA structure to occur under low pH conditions during viral replication. Importantly, systemic immunization by the post-fusion HA antigen results in GC B cells targeting the occluded epitope, and induces a class of protective antibodies that have cross-group specificity and afford protection independent of virus neutralization activity. Furthermore, this class of broadly protective antibodies develops at late time points and persists. Our results identify a class of cross-protective antibodies that are selected at the viral replication site, and provide insights into vaccine strategies using the occluded epitope.
PMID: 31462639 DOI: 10.1038/s41467-019-11821-6