000160923 001__ 160923 000160923 005__ 20251017144624.0 000160923 0247_ $$2doi$$a10.1016/S2214-109X(25)00046-4 000160923 0248_ $$2sideral$$a144125 000160923 037__ $$aART-2025-144125 000160923 041__ $$aeng 000160923 100__ $$aLuabeya, Angelique Kany Kany 000160923 245__ $$aLive-attenuated Mycobacterium tuberculosis vaccine, MTBVAC, in adults with or without M tuberculosis sensitisation: a single-centre, phase 1b–2a, double-blind, dose-escalation, randomised controlled trial 000160923 260__ $$c2025 000160923 5060_ $$aAccess copy available to the general public$$fUnrestricted 000160923 5203_ $$aBackground: An effective adult vaccine is needed to control tuberculosis. We evaluated the safety and immunogenicity of a live-attenuated Mycobacterium tuberculosis vaccine (MTBVAC). Methods: This single-centre, phase 1b–2a, double-blind, dose-escalation, randomised controlled trial (NCT02933281 ) enrolled South African adults previously vaccinated with BCG, who were HIV negative and aged 18–50 years, with or without M tuberculosis sensitisation assessed by QuantiFERON-tuberculosis Gold-Plus assay (QFT). Participants were recruited from the local community and randomly allocated (2:1) to receive MTBVAC (5 × 103, 5 × 104, 5 × 105, or 5 × 106 colony-forming unit [CFU] doses) or BCG revaccination (5 × 105 CFU dose). The primary outcomes were the occurrence of systemic solicited adverse events within 7 days and unsolicited adverse events within 28 days after vaccination, the occurrence of solicited and unsolicited injection-site reactions within 84 days after vaccination, and the occurrence of serious adverse events (SAEs) until the end of study, 365 days after vaccination. Data were analysed per modified intention to treat. The trial is now complete and closed. Findings: Between Jan 15, 2019, and Sept 7, 2020, 485 participants provided consent and were screened. 144 participants were enrolled and 143 (99%) were vaccinated. BCG was administrated to 47 (33%) of 143 and MTBVAC to 96 (67%) of 143. 12 participants with QFT-negative results and 12 with QFT-positive results were randomly allocated to receive each dose of MTBVAC and 24 participants with QFT-negative results and 24 with QFT-positive results were randomly allocated to receive BCG revaccination. Injection-site pain, discharge, erythema, and swelling increased with MTBVAC dose level. MTBVAC 5 × 105 CFU recipients reported a similar proportion of related adverse events (23 [96%] of 24) as BCG recipients (45 [96%] of 47). MTBVAC recipients who were QFT positive reported more injection-site reactions (46 [96%] of 48; 95% CI 85·7–99·5) than MTBVAC recipients who were QFT negative (32 [67%] of 48; 51·6–79·6). No vaccine-related SAEs were reported. All doses of MTBVAC were immunogenic; vaccine-induced antigen-specific CD4 T-cell responses peaked 28 days after vaccination. The MTBVAC 5 × 105 and 5 × 106 CFU doses induced T-helper-cell-1 cytokine-expressing CD4 T-cell responses that exceeded BCG-induced responses in participants who were QFT negative and QFT positive. Interpretation: MTBVAC at the 5 × 105 dose showed similar safety and reactogenicity and greater immunogenicity when compared to BCG. These results suggest that the 5 × 105 dose of MTBVAC could be selected for a subsequent efficacy evaluation. 000160923 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc-nd$$uhttps://creativecommons.org/licenses/by-nc-nd/4.0/deed.es 000160923 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion 000160923 700__ $$aRozot, Virginie 000160923 700__ $$aImbratta, Claire 000160923 700__ $$aRatangee, Frances 000160923 700__ $$aShenje, Justin 000160923 700__ $$aTameris, Michele 000160923 700__ $$aMendelsohn, Simon C 000160923 700__ $$aGeldenhuys, Hennie 000160923 700__ $$aFisher, Michelle 000160923 700__ $$aMusvosvi, Munyaradzi 000160923 700__ $$aYoung, Carly 000160923 700__ $$aMulenga, Humphrey 000160923 700__ $$aBilek, Nicole 000160923 700__ $$aMabwe, Simbarashe 000160923 700__ $$aJelsbak, Ingrid Murillo 000160923 700__ $$aRodríguez, Esteban 000160923 700__ $$aPuentes, Eugenia 000160923 700__ $$aDoce, Juana 000160923 700__ $$0(orcid)0000-0001-7897-9173$$aAguilo, Nacho$$uUniversidad de Zaragoza 000160923 700__ $$0(orcid)0000-0003-2993-5478$$aMartin, Carlos$$uUniversidad de Zaragoza 000160923 700__ $$aPillay, Cadwill 000160923 700__ $$aTait, Dereck 000160923 700__ $$aRussell, Marisa 000160923 700__ $$aVan Der Merve, Arrie 000160923 700__ $$aRutkowski, Kathryn 000160923 700__ $$aHunt, Devin 000160923 700__ $$aGinsberg, Ann 000160923 700__ $$aScriba, Thomas J 000160923 700__ $$aHatherill, Mark 000160923 700__ $$aSwanepoel, Liticia 000160923 700__ $$aDavids, Ilse 000160923 700__ $$aDe Kock, Marwou 000160923 700__ $$aBotes, Natasja 000160923 700__ $$aRossouw, Susan 000160923 700__ $$aBarnard, Liezl 000160923 700__ $$aVerster, Elmien 000160923 700__ $$aVeldsman, Ashley 000160923 700__ $$aMeyer, Faheemah 000160923 700__ $$aKaskar, Masooda 000160923 700__ $$aLeopeng, Thelma 000160923 700__ $$aNoble, Julia 000160923 700__ $$aAfrica, Hadn 000160923 700__ $$aValley, Habibullah 000160923 700__ $$aSteyn, Marcia 000160923 700__ $$aMakhete, Lebohgang 000160923 700__ $$aMangali, Sandisiwe 000160923 700__ $$aNkambule, Hlengiwe 000160923 700__ $$aErasmus, Mzwandile 000160923 700__ $$aJaxa, Lungisa 000160923 700__ $$aRaphela, Rodney 000160923 700__ $$aSchreuder, Constance 000160923 700__ $$aCloete, Yolundi 000160923 700__ $$aNambida, Onke 000160923 700__ $$aCompanie, Alessandro 000160923 700__ $$aKhomba, Gloria 000160923 700__ $$aAbrahams, Charmaine 000160923 700__ $$aMagawu, Patricia 000160923 700__ $$aMactavie, Lauren 000160923 700__ $$aErasmus, Margareth 000160923 700__ $$aVan Rooyen, Johanna 000160923 700__ $$aMouton, Angelique 000160923 700__ $$aOpperman, Fajwa 000160923 700__ $$aSegelaar, Carmen 000160923 700__ $$aTyambetyu, Petrus 000160923 700__ $$aDiamond, Bongani 000160923 700__ $$aVeldtsman, Helen 000160923 700__ $$aReid, Tim 000160923 7102_ $$11011$$2630$$aUniversidad de Zaragoza$$bDpto. Microb.Ped.Radio.Sal.Pú.$$cÁrea Microbiología 000160923 7102_ $$11011$$2566$$aUniversidad de Zaragoza$$bDpto. Microb.Ped.Radio.Sal.Pú.$$cÁrea Inmunología 000160923 773__ $$g13, 6 (2025), e1030-e1042$$pThe Lancet. Glob. health$$tThe Lancet. Global health$$x2214-109X 000160923 8564_ $$s985534$$uhttps://zaguan.unizar.es/record/160923/files/texto_completo.pdf$$yVersión publicada 000160923 8564_ $$s3175380$$uhttps://zaguan.unizar.es/record/160923/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada 000160923 909CO $$ooai:zaguan.unizar.es:160923$$particulos$$pdriver 000160923 951__ $$a2025-10-17-14:23:21 000160923 980__ $$aARTICLE