POTENTIAL USE OF RV2626C ANTIGEN FOR DEVELOPINGVACCINES AGAINST LATENT TUBERCULOSIS.

CASTELLO FLORENCIA; CUSMANO LILIANA; DEL MEDICO PAULA; GARCÍA V; AMIANO NICOLAS; NANCY L. TATEOSIÁN; MARIA PAULA MORELLI; DOMINGO J. PALMERO; JOAQUIN PELLEGRINI; MARIA MAGDALENA GHERARDI; GALLEGO CLAUDIO; CALAMANTE GABRIELA

Congreso; Reunión conjunta SAIC-SAI-SAFIS 2018; 2018

Potential use of Rv2626c antigen for developing vaccines against latent tuberculosis.Tuberculosis (TB) is one of the most prevalent infectious diseases worldwide. Moreover, nearly 1/3 of the world population is latently infected (LTBI) with Mycobacterium tuberculosis (Mtb) and at risk of disease reactivation. The aim of this work was to study the potential of Rv2626c, a protein antigen secreted by Mtb during LTBI, to develop therapeutic vaccines. Previously, we demonstrated that Rv2626c induced IFN responses by peripheral blood mononuclear cells (PBMCs) from LTBI. Besides, several studies have demonstrated that poly-functional T cellular responses are the most efficient in generating protection against intracellular pathogens. Thus, we investigated the generation of poly-functional responses against Rv2626c. To do this, PBMCs were stimulated and the expression of IFN-γ, IL-2 and TNF-α were analyzed by flow cytometry. The results showed that 31% of responder CD4+ LT produced more than one cytokine after treatment with Rv2626c. However, only 19% of CD4+ LT poly-functional cells were identified in TB patients and Healthy Donors (HD). On the other hand, recent works have proposed that humoral immunity against Mtb might have a role in the defense against the pathogen. Then, we analyzed the levels of IgG against Rv2626c in plasma from LTBI, TB and HD. We found that the levels of IgG secreted by LTBI (42.29  12.39 ng/ml) and TB patients (84.36  28.86 ng/ml) were higher as compared to HD (13.71  2.96 ng/ml). Nevertheless, we detected significant differences in the amounts of IgG only between TB and HD. Moreover, in the LTBI group, two population of subjects producing marked different amounts of IgG against Rv2626c were found: healthy workers (HW) (76,7322,64 ng/ml) and close contacts (CC) (13,584,77 ng/ml). We hypothesized that CC are individuals recently infected with Mtb who have not been exposed to Rv262c yet. Considering our results in humans, we initiated in vivo experiments in BALB/c mice using rRv2626c and rAg85A (another deeply studied protein from Mtb) as immunogens and IL-12 as an adjuvant. At different times after immunization, splenocytes were obtained and stimulated ex vivo with Rv2626c. We observed an increased production of IFN in cells cultured either with rRv2626c or rAg85A. Overall, our findings suggest that Rv2626c is a potential candidate for the development of new therapeutic vaccines for the treatment of LTBI.