doi:10.1038/s41541-025-01110-3engFelgueres, María-JoséEsteso, GloriaGarcía-Jiménez, Álvaro F.Benguría, AlbertoVázquez, EnriqueAguiló, NachoPuentes, EugeniaDopazo, AnaMurillo, IngridMartín, CarlosRodríguez, EstebanReyburn, Hugh T.Valés-Gómez, MarCytolytic γδ T-cells and IFNγ-producing CD4-lymphocytes characterise the early response to MTBVAC tuberculosis vaccineART-2025-143557Infection 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 CD16+GZMB+ 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.2025http://zaguan.unizar.es/record/15309610.1038/s41541-025-01110-3http://zaguan.unizar.es/record/153096oai:zaguan.unizar.es:153096info:eu-repo/grantAgreement/ES/MICINN/RTC-2017-6379-1npj Vaccines 10, 1 (2025), 58 [12 pp.]by-nc-ndhttps://creativecommons.org/licenses/by-nc-nd/4.0/deed.esinfo:eu-repo/semantics/openAccess