Felgueres, María-JoséEsteso, GloriaGarcía-Jiménez, Álvaro FBenguría, AlbertoVázquez, EnriqueAguiló, NachoPuentes, EugeniaDopazo, AnaMurillo, IngridMartín, CarlosRodríguez, EstebanReyburn, Hugh TValés-Gómez, Mar2025-07-162025-07-162025-03-28NPJ Vaccines. 2025 Mar 28;10(1):58.https://hdl.handle.net/20.500.12105/26829Infection with Mycobacterium tuberculosis (Mtb) can produce a wide spectrum of clinical manifestations, ranging from active tuberculosis (TB) to asymptomatic latent infection. Although CD4 T-cells are key immune effectors to control TB, early after infection, the innate immune response must play a role in tackling the disease. Here, we performed in-depth analyses of the acute immune response to MTBVAC, a candidate vaccine engineered from Mtb with the aim of protecting adults from pulmonary TB disease, still a major global challenge. scRNA-seq shows expansion of CD4 and cytotoxic γδ T-cells, data confirmed by flow cytometry. CD4 T-cells exhibited lower HLA-DR and higher L-selectin expression, compared to BCG-stimulation, indicating differential activation or dynamics. Importantly, MTBVAC-activated γδ T-cells had a unique cytotoxic CD16GZMB phenotype, reminiscent of effector cells found in Mtb positive individuals controlling infection. IFN-γ and TNF-α were released in cultures, while IL-17A/F were almost undetectable.The group of MVG belongs to the research network Cancer hub-CSIC and to the EU-COST action IMMUNO-model. M.J.F. and A.F.G.J. were registered PhD students at the Molecular Biosciences doctoral program of the Universidad Autónoma de Madrid (UAM).This study was funded by grants RTC-2017-6379-1, PID2021-123795OB-I00 (MVG) and PID2020- 115506RB-I00 (HTR), by MICIU/AEI/ 10.13039/501100011033 and by “ERDF A way of making Europe”; Grant FPU18/01698 (AFGJ) by MICIU/AEI/10.13039/501100011033 and by “ESF Investing in your future” (ESF+); INPhINIT Doctoral Programme from La Caixa Foundation LCF/BQ/DI19/11730039 (MJF); MVG acknowledges financial support from the Spanish State Research Agency, AEI/10.13039/501100011033, through the “Severo Ochoa” Program for Centres of Excellence in R&D [CEX2023-001386-S]. Funders played no role in study design, data collection, analysis and interpretation of data, or the writing of this manuscript.engVoRhttp://creativecommons.org/licenses/by-nc-nd/4.0/Attribution-NonCommercial-NoDerivatives 4.0 International40155627NPJ Vaccinesopen access