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

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Aljurayyan, Abdullah, Puksuriwong, Suttida, Ahmed, Muhammad, Sharma, Ravi, Krishnan, Madhan, Sood, Salil, Davies, Katherine, Rajashekar, Devika, Leong, Sam, McNamara, Paul S, Gordon, Stephen ORCID: https://orcid.org/0000-0001-6576-1116 and Zhang, Qibo (2018) 'Activation and induction of antigen-specific T follicular helper cells (TFH) play a critical role in LAIV-induced human mucosal anti-influenza antibody response'. Journal of Virology, Vol 92, Issue 11, e00114-18.

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Abstract

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.]

Item Type: Article
Subjects: QW Microbiology and Immunology > Immunity by Type > QW 563 Local immunity
QW Microbiology and Immunology > Antigens and Antibodies. Toxins and Antitoxins > QW 570 Serology.
QW Microbiology and Immunology > Antigens and Antibodies. Toxins and Antitoxins > QW 573 Antigens
QW Microbiology and Immunology > Antigens and Antibodies. Toxins and Antitoxins > QW 575 Antibodies
WC Communicable Diseases > Virus Diseases > Viral Respiratory Tract Infections. Respirovirus Infections > WC 515 Human influenza
Faculty: Department: Clinical Sciences & International Health > Malawi-Liverpool-Wellcome Programme (MLW)
Digital Object Identifer (DOI): https://doi.org/10.1128/JVI.00114-18
SWORD Depositor: JISC Pubrouter
Depositing User: Stacy Murtagh
Date Deposited: 06 Apr 2018 13:56
Last Modified: 08 Jun 2018 15:41
URI: http://archive.lstmed.ac.uk/id/eprint/8444

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