Activation and induction of antigen-specific T follicular helper cells (TFH) play a critical role in LAIV-induced human mucosal anti-influenza antibody response

There is increasing interest recently in developing intranasal vaccines against respiratory tract infections. Antibody response is critical in vaccine-induced protection and T is considered important in mediating antibody response. Most data supporting the role for T in antibody response are from animal studies, and direct evidence from humans is limited, apart from T -like cells in blood. We studied activation and induction of T and its role on anti-influenza antibody response by live-attenuated influenza vaccine(LAIV) in human nasopharynx-associated lymphoid tissue(NALT). T activation in adenotonsillar tissues were analysed by flow-cytometry, and anti-hemagglutinin(HA) antibodies examined following LAIV stimulation of tonsillar mononuclear cells(MNC). Induction of antigen-specific T by LAIV was studied by flow-cytometry for induced T and CD154 expression. LAIV induced T proliferation which correlated with anti-HA antibody production, and T was shown critical for antibody response. Induction of T from naïve T cells by LAIV was shown in newly induced T expressing BCL6 and CD21, which was followed by the detection of anti-HA antibodies. Antigen specificity of LAIV-induced T was demonstrated by the expression of antigen-specific T cell activation marker CD154 upon challenge by H1N1 virus antigen or HA. LAIV-induced T differentiation was inhibited by BCL6, IL21, ICOS and CD40 signalling blocking respectively, and that diminished anti-HA antibody production. We demonstrate for the first time the induction of antigen-specific T by LAIV in human NALT that provide critical support for anti-influenza antibody response. Promoting antigen-specific T in NALT by intranasal vaccines may provide an effective vaccination strategy against respiratory infections in humans. Airway infection such as influenza is common in humans. Intranasal vaccination has been considered a more biologically relevant and effective way of immunization against airway infection. Vaccine-induced antibody response is crucial for protection against infection. Recent data from animal studies suggest one type of T cells, named T is important for the antibody response. However, data on whether this T -mediated help for antibody production operates in humans is limited, due to the lack of access to human immune tissue containing the T In this study, we demonstrated the induction of T cells by an intranasal influenza vaccine in human immune tissue that provide critical support for anti-influenza antibody response. Our findings provide direct evidence that T cells play a critical role in vaccine-induced immunity in humans, and suggest a novel strategy to promote such cells by intranasal vaccines against respiratory infections. [Abstract copyright: Copyright © 2018 Aljurayyan et al.]