SEMEN IMPROVES THE PROTECTIVE IMMUNE RESPONSE GENERATED BY A SYSTEMIC VACCINATION AGAINST HSV-2

F. DI DIEGO GARCÍA; I. MAZZITELLI; A. VARESE; A. PALETTA; A. G. COLUSSI; J. SABATTÉ; F. REMES LENICOV; J. GARCIA; A. CEBALLOS

Mar del Plata

Congreso; LXIX Reunión Científica de la Sociedad Argentina de Inmunología; 2022

Sociedad Argentina de Inmunología

Semen is able to induce immunological tolerance which is determinant in fecundation. But it is also the principal vector of sexually transmitted infections (STI). Are the immunosuppressive properties of semen able to facilitate STI? In previous work, we demonstrated that the seminal vesicle fluid (VS) does not facilitate the infection, but improves the protective effect induced by an intravaginal vaccination with inactivated HSV-2 in a murine model. This effect could be due to a local inflammatory response and a robust memory immune response mediated by CD8+ T cells. Now, we are exploring whether semen is able to promote the homing of activated T cells at the vaginal tract after systemic immunization. Vagina is restrictive for memory T cell entry; this can be overcome in inflammatory processes, leading to the establishment of resident memory T cells. Our hypothesis sustains that semen by inducing a local inflammatory response will promote the recruitment of memory T cells generated in response to systemic immunization. We design a strategy based on two steps: 1) subcutaneous vaccination with UV-inactivated HSV-2 (106 PFU) and 2) vaginal application of VS in ten-week-old female BALB/c mice (6 per group). Twenty five days later, mice were challenged with a lethal dose of HSV-2 (2x105PFU).Clinical score, weight and survival were measured Mice stimulated with VS after vaccination showed higher survival probability after the challenge compared with the PBS group (67% vs 17%; p=0.0105; n=2 independent experiments). The VS group have lost less weight and showed less signs of effective infection. In addition, none of the animals in this group showed hind limb paralysis, an indicator of irreversible infection. Our preliminary results showed that the VS improved the protective response conferred by the vaccine. This subject acquires special relevance in the design of vaccines that confer protection against sexually transmitted infections at vaginal mucosa.