Intranasal co-administration of IL-12 plus CTB in DNA-MVA mucosal schemes enhanced cellular immune responses against the HIV-1 Env antigen, systemically and in mucosal draining lymph nodes

ANA MARÍA RODRIGUEZ; CYNTHIA MAETO; JULIANA FALIVENE; MARÍA FERNANDA PASCUTTI; M.MAGDALENA GHERARDI

Buenos Aires

Congreso; 1 Congreso Fanco Argentino de Inmunologia; 2010

SAI-Francia

The major route of HIV transmission is through the exposure of mucosal surfaces to the virus, therefore designing mucosal immunization regimes aimed to induce mucosal immune responses is highly needed. The aim of this study was to analyze the mucosal activity of IL-12 alone or in combination with the subunit B of cholera toxin (CTB), applied in DNA-prime/MVA-boost intranasal immunization schemes. Balb/c mice were immunized by intranasal route with a heterologous DNA prime-MVA boost regimen, in which both vectors express the HIV-1 Env subtype B protein. Two doses of DNA-IL-12 were applied (50g or 100g) at priming, in the presence or not of 10 g of CTB applied at prime and booster doses. Groups receiving CTB, complete cholera toxin (CT) or non-adjuvants were included. Co-inoculated DNAIL-12 with CTB (IL-12+CTB) produced the highest specific TCD8+ immune response (evaluated as IFN- secreting cells by ELISPOT), detected in the spleen as well as in regional (cervical) and genital (iliac) draining lymph nodes. In general, the co-administration of both adjuvants followed an additive effect in the final response obtained. Both DNA-IL-12 doses generated similar responses, even more the minor IL-12 dose applied plus CTB generated the highest response in the spleen showing a synergistic effect for both adjuvants, indicating that 50 ug is sufficient. Increments in the TCD8+ response detected in IL-12+CTB groups were up to 7 fold in the spleen, and up to four (cervical) and three fold (genital) in mucosal draining lymph nodes. Remarkably, these responses were equivalent or even higher than those detected in the groups with CT. Finally, the highest specific TCD8+ response found in the IL-12+CTB group was accompanied by an increase in the Th1/Th2 specific cytokine secretion against gp120. These results are of importance due to the need to improve mucosal vaccine strategies against HIV.