Semen acts as an adjuvant in an intravaginal immunization model

AUGUSTO VARESE; MELINA GONZALEZ PRINZ; REMES LENICOV; PALLETA ANA; CEBALLOS ANA

Paris

Conferencia; IAS; 2017

Seminal Vesicle Fluid acts as anadjuvant in an intravaginal immunization model Semen is the main vector of STDs but also inducesbiological actions on the female reproductive tissues directed to modulate theimmune response against paternal antigens. However, the influence of seminalplasma on the immune response against sexually transmitted pathogens has notbeen properly evaluated. Our aim was to analyze whether seminal vesicle fluid(SVF) might compromise the induction of a protective memory response againstsexually transmitted pathogens, using an HSV-2 intravaginal vaccination model.SVF was extracted post-mortem from 10-week-old BALB/cmales. Female BALB/c were vaccinated IVAG with inactivated HSV-2 (1x104pfu/15 μl), without or with SVF (5mg/ml). Thirtydays later, mice were challenged IVAG with HSV-2 lethal dose. Mice were examined for clinical score and survival. Draining lymph nodes (DLN) and genital mucosa cells were analyzedby flow cytometry, ELISA, and qPCR. We observed that SVF-vaccinated mice showed 80%survival (control 30%; n=20; p<0.001), and minor disease progression (2.27±0.1 n=20; p<0.001). These mice had increased IFN-γ (n=3, p<0.05), TNF-α (n=3, p<0.001), IL-17 (n=3p<0.05), IL-6 (n=3, p<0.05) and lower IL-10 (n=3, p<0.05) production invaginal mucosa. Also, we found that SVF-vaccinatedmice showed a higher frequency of memory/effectorlike Tcells (CD44highCD62Llow) and central memory Tcells(CD44highCD62Lhigh) in both CD4+ (n=3 p<0,001) andCD8+ (n=3 p<0.05) Tcell compartments. These changes were associated to anincrease in the production of TNF-α and IFN-γ (n=3 p<0,001 andp<0,0005, respectively). Even more, adoptive transfer of CD4+ and CD8+Tcells from HSV-2 SVF immunized mice showed to be sufficient for granting protection of naive mice againstlethal HSV-2 challenge (n=20; p<0,05).In addition, we observed that SVFsignificantly increased the expression of CD86 (MFI 5982 vs 3808, n=3) in vaginalDCs 48 hs post vaccination and the frequency and the total number of DCs in DLN(n= 3, p<0.05).In contrast with the notion that semenacts as an immunosuppressive agent, our results suggest that SVF induces anadjuvant effect on the female immune response against sexually transmittedpathogens. These observations may lead to better comprehension of the immuneresponse against STDs providing a more rational basis for the development ofmucosal vaccines.