Potential use of Rv2626c antigen for developing therapeutic vaccines for latent tuberculosis

MARÍA PAULA MORELLI; AMIANO, NICOLÁS; PELLEGRINI, JOAQUÍN; NANCY TATEOSIAN; AGUSTÍN ROLANDELLI; FLORENCIA CASTELLO; DOMINGO J. PALMERO; MARIA MAGDALENA GHERARDI; VERÓNICA E. GARCIA

San Pablo

Workshop; IUIS Brazil ? Advanced Course in Vaccines; 2017

Tuberculosis (TB) is one of the most prevalent infectious diseases worldwide an estimated 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 is to study the potential of Rv2626c,a protein secreted by Mtb during LTBI,todevelop therapeutic vaccines for the treatment of LTBI.Accordingly, several studies have demonstrated that poly-functional T cellular responses are the most efficient in generating protection against intracellular pathogens. Indeed, we previously demonstrated that stimulation with Rv2626c induced IFN responses in peripheral blood mononuclear cells (PBMCs) from LTBI. Thus, to study whether poly-functional responses might be generated, PBMCs from LTBI were stimulatedwith Rv2626c and the expression of IFNγ, IL2 and TNFα 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 detected 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 started to investigate the production of IgG against Rv2626c in plasma from our individual population. We found that the plasma levels of IgG against Rv2626c secreted both by LTBI (DO:0.730.11) and TB patients(0.850.15) were significantly higher as compared to HD (0.480.07). Besides the described preliminary studies in humans, we also initiated in vivo experiments in BALB/c mice using Rv2626c as immunogen. Splenocyteswere then stimulated ex vivowith Rv2626c.We observed anincreased production of IFNand MHC class I protein H-2Kd (48%) expression only in cells cultured with Rv2626c. Overall, these preliminary results suggest that Rv2626c could be a candidate to be used in the development of new therapeutic vaccines for treatment of LTBI.