Targeting Latent Tuberculosis: Immunogenic Evaluation of a Mycobacterium tuberculosis Dormancy Antigen as a Vaccine...

An estimated 2.1 billion people are infected with Mycobacterium tuberculosis (Mtb) and at risk of developing active tuberculosis (TB). Because Mtb exists in replicating and dormant states, effective vaccines should target antigens from both stages. Here, we evaluated the immunogenicity and vaccine potential of Mtb dormancy antigen Rv2626c. Cellular and humoral immune responses were studied in individuals with latent TB infection (LTBI), active TB, and healthy donors (HD) using flow cytometry and ELISA. Overlapping peptides spanning Rv2626c sequence and structural mapping were employed to characterize Rv2626c immunogenic regions. Additionally, the protective efficacy of a Modified Vaccinia Ankara (MVA) vector expressing Rv2626c was evaluated in a murine challenge model. Rv2626c induced cellular immunity selectively in LTBI, characterized by increased frequencies of CD4⁺IFN-γ⁺, SLAMF1⁺, and poly-functional T lymphocytes. Immunodominant peptide regions were identified across the protein sequence. Moreover, mice immunized with MVA-Rv2626c showed a significant reduction in splenic bacterial burden following a challenge with Mtb H37Rv. Altogether, our findings indicate that the latency-associated antigen Rv2626c elicits immune responses in LTBI subjects and limits bacterial dissemination in our mice model of infection. Therefore, Rv2626c arises as a promising candidate to be combined with active phase antigens in multistage vaccines against Mtb infection.