Whole-Virion Influenza Vaccine Recalls an Early Burst of High-Affinity Memory B Cell Response through TLR Signaling

• Published in: The Journal of immunology (1950) Vol. 196; no. 10; pp. 4172 - 4184
• Main Authors: Onodera, Taishi, Hosono, Akira, Odagiri, Takato, Tashiro, Masato, Kaminogawa, Shuichi, Okuno, Yoshinobu, Kurosaki, Tomohiro, Ato, Manabu, Kobayashi, Kazuo, Takahashi, Yoshimasa
• Format: Journal Article
• Language: English
• Published: United States 15.05.2016
• Subjects: Animals; Antibodies, Viral - metabolism; Antibody Affinity; B-Lymphocytes - immunology; B-Lymphocytes - transplantation; Cells, Cultured; Humans; Immunity, Humoral; Immunologic Memory; Influenza Vaccines - immunology; Membrane Glycoproteins - genetics; Membrane Glycoproteins - metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; RNA, Viral - immunology; Signal Transduction; T-Lymphocytes, Helper-Inducer - immunology; Toll-Like Receptor 7 - genetics; Toll-Like Receptor 7 - metabolism; Vaccination; Virion - immunology
• ISSN: 0022-1767; 1550-6606; 1550-6606
• DOI: 10.4049/jimmunol.1600046

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.