IL-7 as a mucosal adjuvant in pulmonary immunization protocols

A Sandouk (1) , A Vieira Antão (1) , S. Figueiredo (1) , B Charmeteau-De-Muylder (1) , F Alby-Laurent (1) , M Benard (1) , E. Véron (1) , Magali Rancez (1) , R Cheynier (1) , A Couëdel-Courteille (1)

1 IC UM3 (UMR 8104 / U1016) - Institut Cochin

Objective: Mucosae are the gateway for many pathogens. However, few vaccines have been developed to specifically target mucosal immunity. Recent studies in the laboratory evidenced local expression of IL-7 in the acutely SIV-infected intestinal mucosa and IAV-infected lung in macaques or mice, respectively. This overexpression led to chemokine production and infiltration of immune cells into these mucosae. In addition, systemic injection of IL-7 to macaques rapidly stimulates both the production of chemokines and immune cells homing into the mucosa. These results prompted us to study if IL-7 could be used as a mucosal vaccine adjuvant. Methods: Mice were intratracheally treated with IL-7 or PBS, then immunized by the same route against diphtheria toxoid (DT) or inactivated influenza virus (IAVi) two days later. DT immunized-mice were sacrificed at day 14 while those immunized with IAVi were infected with virulent IAV at day 14 and sacrificed at day 29. We measured antigen-specific antibody responses (anti-DT & anti-IAV) in both bronchoalveolar lavages (BAL) and sera, as well as chemokine expressions in lung tissue, by ELISA. The immune cell infiltration into the pulmonary mucosa was evaluated by immunochemistry on lung sections. The effectiveness of IL-7-adjuvanted vaccine in providing protection against IAV pathology was assessed by daily monitoring of animal body weight. Results: Intratracheal administration of IL-7 stimulated the production of pro-inflammatory chemokines in the lung parenchyma, leading to massive infiltration of immune cells found to be mainly organized in lymphoid aggregates. Moreover, intratracheal administration of IL-7 before primo-immunization allowed antigens-specific IgAs and IgGs production in the pulmonary mucosa. These effects were not observed in control mice vaccinated without IL-7 administration. In addition, only IL-7-treated immunized mice were protected against influenza pathology. This protection seems to be related to a high level of IAV-specific antibodies in BAL and lymphoid aggregate appearance in the pulmonary mucosa. Conclusion: By attracting immune cells into mucosae, local IL-7 administration prepares the mucosal immune system, gathering conditions that result in enhanced antigen-specific pulmonary immune responses upon antigenic stimulation. Hence, IL-7 appears as a mucosal adjuvant able to increase mucosal antibody responses, an important immune arm implicated in the protection against most mucosal infections.

Domaines: Sciences du Vivant [q-bio]

A Sandouk, A Vieira Antão, S. Figueiredo, B Charmeteau-De-Muylder, F Alby-Laurent, et al.. IL-7 as a mucosal adjuvant in pulmonary immunization protocols. 52rd Annual Meeting of the French society for immunology (SFI 2019), Nov 2019, Nantes, France. ⟨hal-02998897⟩