Intranasal co-administration of IL-12 plus CTB in DNA-MVA mucosal schemes enhanced systemic and mucosal cellular immune responses against HIV-1 Env

CYNTHIA MAETO; ANA MARÍA RODRIGUEZ; JULIANA FALIVENE; MARÍA FERNANDA PASCUTTI; GHERARDI MM

Bangkok

Conferencia; AIDS Vaccine Conference 2011; 2011

BACKGROUND: The major route of HIV transmission is through mucosal tissues. Therefore, designing immunization regimes aimed to induce mucosal immune responses is needed. The aim of this study was to analyze the activity of IL-12 alone or in combination with the cholera toxin B subunit (CTB), applied in DNA-prime/MVA-boost intranasal immunizations. METHODS: Balb/c mice were intranasally immunized with both vectors expressing HIV-1 EnvB.  Two doses of DNA-IL-12 were applied (50ug or 100ug) in the presence or not of 10ug of CTB applied at prime and booster doses. Groups receiving CTB, complete cholera toxin (CT) or non-adjuvants (control) were included. Immune responses were evaluated 14 or 30 days after immunization. RESULTS: Both DNA-IL-12 doses generated similar responses, even more the minor one plus CTB generated the highest response, showing a synergistic effect for both adjuvants. Co-inoculated IL-12+CTB (G4) produced the highest specific TCD8+ immune response (by IFN-g ELISPOT), detected in the spleen (up to a seven-fold increment), as well as in regional (cervical) and genital (iliac) lymph nodes (GLNs), and more importantly in genital tract mucosa (GT). IL-2 secreting cells were two-fold superior in G4 compared to control group in spleen (p=0.0321), GLNs (p=0.005) and GT. A higher proportion of cytotoxic and polyfunctionality cells were detected in spleen and GT. At memory phase, we found that in the G4 IFN-g and IL-2 secreting cells were two to three-fold superior in both systemic (spleen, p=0.001) as well as in mucosal compartments (GLNs). Finally, IL-12 and CTB also enhanced gp120 Abs levels (serum IgGs and IgA in vaginal washings). CONCLUSIONS: Here we demonstrated that IL-12 cytokine in combination with CTB generated a cooperative adjuvant effect on the cellular and humoral IR against Env antigen applied in DNA-MVA intranasal immunizations. These results are important due to the need to improve mucosal vaccine strategies against HIV.