Abstract EN:

The female genital mucosa is the major site of HIV infection. It is accepted that vaccination by mucosal route is more effective than parenteral vaccination to generate an immune barrier including genital secretory immunoglobulins (SIgA) and mucosal cytotoxic T lymphocytes (CTL). A better understanding of the role of dendritic cells (DC), effective antigen presenting cells located at the site of mucosal immunization in the induction of genital immunity should facilitate the development of mucosal vaccines targeting DC. In that context, this work demonstrates that vaginal or sublingual administration of a prototype vaccine (comprising ovalbumin or HIV peptidic sequences of gp41 or reverse transcriptase proteins) generates specific humoral and cytotoxic responses in the genital mucosa. DC present at both sites of immunization play a major role in the induction of these responses. More precisely, vaginal Langerhans cells are not only dispensable for the generation of genital CTL responses but they down-regulate these responses, by a mechanism which may involve IL-10 and IL-17 cytokines. Furthermore, sublingual DC have exceptional migratory properties to distant lymphoid organs, a phenomenon which may partly explain the ability of sublingual vaccination to induce disseminated genital CTL responses. These data underline the potential of the sublingual mucosa to serve as an inductive site for inducing systemic and genital immunity against sexually transmitted infections in general and against HIV in particular. Furthermore, these findings might be critical for the development of new mucosal vaccines and immunotherapeutic strategies designed for the targeting of DC subsets.