doi:10.1016/j.xcrm.2020.100187engDijkman, K.Aguilo, N.Boot, C.Hofman, S.O.Sombroek, C.C.Vervenne, R.A.W.Kocken, C.H.M.Marinova, D.Thole, J.Rodríguez, E.Vierboom, M.P.M.Haanstra, K.G.Puentes, E.Martin, C.Verreck, F.A.W.Pulmonary MTBVAC vaccination induces immune signatures previously correlated with prevention of tuberculosis infectionART-2021-123268To fight tuberculosis, better vaccination strategies are needed. Live attenuated Mycobacterium tuberculosis-derived vaccine, MTBVAC, is a promising candidate in the pipeline, proven to be safe and immunogenic in humans so far. Independent studies have shown that pulmonary mucosal delivery of Bacillus Calmette-Guérin (BCG), the only tuberculosis (TB) vaccine available today, confers superior protection over standard intradermal immunization. Here we demonstrate that mucosal MTBVAC is well tolerated, eliciting polyfunctional T helper type 17 cells, interleukin-10, and immunoglobulins in the airway and yielding a broader antigenic profile than BCG in rhesus macaques. Beyond our previous work, we show that local immunoglobulins, induced by MTBVAC and BCG, bind to M. tuberculosis and enhance pathogen uptake. Furthermore, after pulmonary vaccination, but not M. tuberculosis infection, local T cells expressed high levels of mucosal homing and tissue residency markers. Our data show that pulmonary MTBVAC administration has the potential to enhance its efficacy and justifies further exploration of mucosal vaccination strategies in preclinical efficacy studies.2021http://zaguan.unizar.es/record/9974810.1016/j.xcrm.2020.100187http://zaguan.unizar.es/record/99748oai:zaguan.unizar.es:99748info:eu-repo/grantAgreement/EC/H2020/643381/EU/TBVAC2020; Advancing novel and promising TB vaccine candidates from discovery to preclinical and early clinical development/TBVAC2020This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 643381-TBVAC2020info:eu-repo/grantAgreement/EC/H2020/730964/EU/European Vaccine Research and Development Infrastructure/TRANSVAC2This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 730964-TRANSVAC2Cell reports medicine 2, 1 (2021), 100187 [18 pp]by-nc-ndhttp://creativecommons.org/licenses/by-nc-nd/3.0/es/info:eu-repo/semantics/openAccess