IL-7 as an adjuvant for mucosal vaccine development

Magali Rancez (1) , S Logerot (1) , S. Figueiredo (1) , B Charmeteau-De-Muylder (1) , I Bourgault-Villada (1) , A Couëdel-Courteille (1, 2) , R Cheynier (1) , Carolina Moraes-Cabe (1)

1 IC UM3 (UMR 8104 / U1016) - Institut Cochin
2 UPD7 - Université Paris Diderot - Paris 7

Background: Despite considerable research efforts, mucosal immunity remains particularly difficult to stimulate through vaccines. Systemic injection of IL-7 stimulates chemokines-induced recruitment of circulating T-cells into mucosae. Methods: The optimal dose of IL-7 to be sprayed on mucosal surface was defined on 14 rhesus macaques. On mucosal biopsies collected after IL-7 administration, we quantified local transcription of 19 chemokines by qRT-PCR and cell infiltration by immunochemistry plus image analysis. Six macaques were immunized with antigens (DT and the HIV-1 gp41-P1 peptide) applied directly on the vaginal mucosa, two days after either IL-7 or PBS administration. The immunizations were repeated thrice, four months apart, and the macaques were euthanized 2 weeks after the last immunization. Antigen-specific IgA and IgG productions were quantified in vaginal secretions by ELISA. Antigen-specific plasma cells were detected by reverse immunohistochemistry in tissue, and by B-cell ELISPOT in PBMCs. Results: A significant overexpression of twelve chemokines was observed 48 hours after mucosal administration of 10µg of IL-7. Subsequently, mDC, macrophage, NK, B- and T-cell numbers significantly raised in the IL-7-treated mucosae, suggesting massive chemokine-driven infiltration. Administration of antigens led to a stronger mucosal immune response in the IL-7-treated macaques as compared to animals immunized with antigens alone. Robust production of antigen-specific IgAs and IgGs was detected in vaginal secretions. The immunizations repeated thrice sustained mucosal specific immune responses. Antigen-specific-antibody secreting cells were recovered from PBMC and more DT-specific plasma cells were found in the vaginal mucosae (IgA isotype) and the draining lymph nodes (IgG isotype) of IL-7-treated macaques. Tertiary lymphoid organs were observed in vaginal mucosae from IL-7-treated macaques only. Conclusions: Pre-treatment by non-traumatic vaginal administration of IL-7 (10µg by spray), allows for the development of a strong mucosal immune response in macaques following subsequent mucosal vaccination, through local chemokine expression and the recruitment of immune cells in the vaginal mucosa. The mucosal localization of IgA-specific plasma cells argues for their main contribution in the high levels of specific-IgAs evidenced in the vaginal secretions. These data suggest that IL-7 could be used as a mucosal adjuvant to elicit vaginal antibody response, the most promising way to confer protection to numerous STD.

Domaines: Sciences du Vivant [q-bio]

Magali Rancez, S Logerot, S. Figueiredo, B Charmeteau-De-Muylder, I Bourgault-Villada, et al.. IL-7 as an adjuvant for mucosal vaccine development. 22nd International AIDS Conference (AIDS 2018), Jul 2018, Amsterdam, Netherlands. 2018. ⟨hal-03000425⟩