title: Whole-Virion Influenza Vaccine Recalls an Early Burst of High-Affinity Memory B Cell Response through TLR Signaling.
abstract: Inactivated influenza vaccines have two formulations, whole- and split-virion types; however, how differential formulations impact their booster effects remain unknown. In this study, we demonstrate that whole-virion vaccines recall two waves of Ab responses, early T cell-independent (TI) and late T cell-dependent responses, whereas split-virion vaccines elicit the late T cell-dependent response only. Notably, higher-affinity Abs with improved neutralizing activity are provided from the early TI response, which emphasizes the important contribution of the formulation-dependent response in the protective immunity. Moreover, we show that the early TI response completely requires B cell-intrinsic TLR7 signaling, which can be delivered through viral RNAs within whole-virion vaccine. Thus, our results indicate that TLR agonists in whole-virion type improve recall Ab responses by directly targeting memory B cells, a finding with important implications for vaccine strategies aimed at the prompt recall of high-affinity neutralizing Abs.
authors.affiliation: Department of Immunology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan;
authors.forename: Taishi
authors.initials: T
authors.lastname: Onodera
authors.affiliation: Laboratory of Biological Chemistry on Food Functionalities, College of Bioresource Sciences, Nihon University, Kanagawa 252-8510, Japan;
authors.forename: Akira
authors.initials: A
authors.lastname: Hosono
authors.affiliation: Influenza Virus Research Center, National Institute of Infectious Diseases, Tokyo 208-0011, Japan;
authors.forename: Takato
authors.initials: T
authors.lastname: Odagiri
authors.affiliation: Influenza Virus Research Center, National Institute of Infectious Diseases, Tokyo 208-0011, Japan;
authors.forename: Masato
authors.identifier: 0000-0001-8133-1263
authors.initials: M
authors.lastname: Tashiro
authors.affiliation: Laboratory of Biological Chemistry on Food Functionalities, College of Bioresource Sciences, Nihon University, Kanagawa 252-8510, Japan;
authors.forename: Shuichi
authors.initials: S
authors.lastname: Kaminogawa
authors.affiliation: Kanonji Institute, The Research Foundation for Microbial Diseases, Osaka University, Kanonji, Kagawa 768-0065, Japan;
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Okuno
authors.affiliation: Laboratory of Lymphocyte Differentiation, Immunology Frontier Research Center, World Premier Institute, Osaka University, Osaka 565-0871, Japan; and Laboratory for Lymphocyte Differentiation, RIKEN Center for Integrative Medical Sciences, Kanagawa 230-0045, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kurosaki
authors.affiliation: Department of Immunology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan;
authors.forename: Manabu
authors.initials: M
authors.lastname: Ato
authors.affiliation: Department of Immunology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan;
authors.forename: Kazuo
authors.identifier: 0000-0002-9249-4030
authors.initials: K
authors.lastname: Kobayashi
authors.affiliation: Department of Immunology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan; ytakahas@niid.go.jp.
authors.forename: Yoshimasa
authors.identifier: 0000-0001-6342-4087
authors.initials: Y
authors.lastname: Takahashi
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000378:metabolism; D000915:Antibody Affinity; D001402:B-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D002478:Cells, Cultured; D006801:Humans; D056724:Immunity, Humoral; D007156:Immunologic Memory; D007252:Influenza Vaccines / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012367:RNA, Viral / Q000276:immunology*; D015398:Signal Transduction; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D051199:Toll-Like Receptor 7 / Q000235:genetics / Q000378:metabolism; D014611:Vaccination; D014771:Virion / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines; D008562:Membrane Glycoproteins; D012367:RNA, Viral; C477038:Tlr7 protein, mouse; D051199:Toll-Like Receptor 7