POTENTIAL USE OF IL-12 AS AN ADJUVANT IN TUBERCULOSIS VACCINES

MORELLI, MARIA PAULA; AMIANO, NICOLÁS; MARIA PAULA DEL MEDICO ZAJAC; JOAQUIN M. PELLEGRINI; NANCY TATEOSIAN; CASTELLO, FLORENCIA; GABRIELA CALAMANTE; MARIA MAGDALENA GHERARDI; GARCÍA, VERÓNICA EDITH

Tucuman

Congreso; LVII REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INMUNOLOGÍA; 2019

SOCIEDAD ARGENTINA DE INMUNOLOGÍA

BACKGROUND: Mycobacterium tuberculosis (Mtb) active infection is one of the leading causes of death worldwide. The attenuated modified vaccinia Ankara (MVA) vaccine vector expressing the mycobacterial antigen 85A (MVA85A) was demonstrated to be safe but it did not improve BCG efficacy. We investigated IL-12 role as an adjuvant of MVA85A and the latent Mtb antigen Rv2626c to be used in a potential multistage vaccine.METHODS: BALB/c Immunization schedules: i) three-doses of recombinant Ag85A andRv2626c together with IL-12 expression plasmid (pCI-IL12) intramuscularly; ii) three-doses of pCI-Ag85A/pCI-IL12 intramuscularly plus on MVA85A or MVA∆85A (∆IL-18bp) intraperitoneal boost. After 10 days, splenocytes were obtained and in vitro stimulated (5x106 cell/ml) with rAg85A and/or rRv2626c. Then, plasma IgG (ELISA), CD8+CD107+  lymphocytes (16h, Flow Cytometry) and IFN-γ production (72h, ELISA) were assayed.RESULTS: IgG levels anti- Rv2626c or Ag85A were independent of IL-12. However,administration of pCI-IL12 with rRv2626c+rAg85A increased IFN-γ secretion by splenocytes stimulated with each protein or with both antigens (p<0,05). Besides, MVA85A and pCI-IL12 had a synergistic effect on IFN-γ production and on the expansion of CD8+CD107+ lymphocytes (p<0,05). Furthermore, MVA∆IL-18bp induced higher IFN-γ secretion compared to MVA85A (p<0,05).CONCLUSIONS: Our findings suggest that IL-12 could function as a potential adjuvant in new vaccines against Mtb infection.