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    Interleukin 7, an effective adjuvant for mucosal vaccination

    Rémi Cheynier's group

    Interleukin 7, an effective adjuvant for mucosal vaccination

    In order to develop an original approach to mucosal vaccination, Rémi Cheynier's team exploited a less known property of IL-7. Applied locally, IL-7 can induce the massive immune cells relocation in mucosae and can therefore promote the processing of mucosally administered antigens. In this study published in Frontiers in Immunology, IL-7, administered on the vaginal mucosa of monkeys together with an antigen, allowed the establishment of a rapid and strong mucosal immune response, characterized by the formation of lymphoid structures in the mucosa and the local production of DT-specific antibodies. This work, demonstrating that IL-7 prepares the mucosa to efficiently respond to mucosal antigenic stimulation, indicates that IL-7 could be used as a mucosal vaccine adjuvant, thus providing a very promising strategy to confer protection against sexually transmitted infections.

     

    Most viral and bacterial infections start with the pathogen entering through the mucosae. To efficiently protect against these infections, the setting up of an immunological barrier at mucosal surfaces should block pathogens at entry. Despite many attempts, the lack of an efficient mucosal adjuvant makes local vaccination approaches rather unsuccessful. In addition, systemic immunization protocols do not allow the establishment of a protective mucosal immunity. It is therefore essential to develop adjuvants that promote the mounting of the immune response induced by mucosal vaccination.

    In this study, the team tested the ability of IL-7 to induce, in the female genital tract, favorable conditions to the development of such a protective response following local administration of antigens. This work is based on identification, by the team, of a secondary function of IL-7 which, aside from its well-known T cells homeostatic function, is a danger signal triggered by mucosal infections. IL-7, rapidly produced in infected mucosa, stimulates the local production of chemokines and allows the immune cell recruitment in these tissues in the first days of infection.

    In this article, the team shows that applied directly to the monkey vaginal mucosa by spray, IL-7 is very effective to stimulate an increase in the production of chemokines in the mucosa, resulting in the recruitment in the tissue of all the immune cellular players. Thanks to this recruitment, the administration of an antigen (diphtheria toxoid: DT) 48 hours after that of IL-7 triggers an earlier and stronger mucosal immune response compared to control monkeys (receiving saline buffer instead of IL-7; PBS + DT). Interestingly, this antibody response is preferentially localized in the vaginal mucosa. Anti-DT antibodies found in vaginal secretions are produced by plasma cells (DT-specific Antibody-Secreting Cells) present in the vaginal mucosa. Finally, numerous organized lymphoid structures, rich in B lymphocytes, characterized the vaginal mucosa of IL-7 treated monkey. The presence of such structures, known to play a major role in the development of mucosal immune responses, confirms the adjuvant effect of IL-7.

    Due to its ability to stimulate the development of strong mucosal immunity against a specific antigen, IL-7 could be used as a mucosal vaccine adjuvant, thereby inducing effective protection against sexual infections.

     

    In rhesus macaques, IL-7 administration on the vaginal mucosa stimulates local production of chemokines (A) and the migration of immune cells (B) toward this mucosa. Treatment of the vaginal mucosa with IL-7 by spray, prior to local immunization with antigen (DT) allows generating lymphoid follicles (D) containing DT-specific IgA plasma cells (C) in the vaginal mucosa. DT-specific antibodies are detectable in the vaginal secretions of macaques immunized by local administration of the antigen by spray, after topical treatment with IL-7 (E).

     

    Reference

    IL-7-Adjuvanted Vaginal Vaccine Elicits Strong Mucosal Immune Responses in Non-Human Primates. Logerot S, Figueiredo-Morgado S, Charmeteau-de-Muylder B, Sandouk A, Drillet-Dangeard AS, Bomsel M, Bourgault-Villada I, Couëdel-Courteille A, Cheynier R, Rancez M. Front Immunol. 2021 Feb 25;12:614115. doi: 10.3389/fimmu.2021.614115. eCollection 2021. PMID: 33717097

     

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