153114 20251017144623.0 doi 10.1016/j.ebiom.2025.105628 sideral 143585 ART-2025-143585 eng Tameris, Michele Safety, reactogenicity, and immunogenicity of MTBVAC in infants: a phase 2a randomised, double-blind, dose-defining trial in a TB endemic setting 2025 Access copy available to the general public Unrestricted Safer and more effective tuberculosis (TB) vaccines than Bacille Calmette Guérin (BCG) are needed. We evaluated the safety, reactogenicity, and immunogenicity of three dose levels of the live-attenuated Mycobacterium tuberculosis (Mtb) vaccine, MTBVAC, compared to BCG, in South African infants. Methods. Healthy, HIV-unexposed, BCG-naïve infants were randomised to receive a single intradermal dose of BCG (2.5 × 105 CFU, n = 24) or MTBVAC (2.5 × 104, 2.5 × 105, or 2.5 × 106 CFU, each n = 25). Safety endpoints were solicited systemic, solicited injection site, and unsolicited adverse events (AE), and serious AE (SAE). Immunogenicity was measured using interferon-γ release assay (IGRA) and whole blood intracellular cytokine staining assay. Follow-up was 12 months post-vaccination. Findings. Ninety-nine infants were enrolled between 18 February 2019 and 08 March 2021. Seventy-eight infants experienced reactogenicity AE (all mild except one grade 2 erythema). Induration, swelling, and erythema were more frequent as MTBVAC dose increased. All reactogenicity events were less frequent in infants receiving MTBVAC 2.5 × 105 CFU compared with BCG. Twelve infants (three BCG and nine MTBVAC recipients) experienced 14 vaccine-unrelated SAE, including one death due to bronchopneumonia (MTBVAC recipient). Eight infants were treated for unconfirmed pulmonary TB (four BCG and four MTBVAC 2.5 × 104 CFU recipients); one BCG recipient was treated for unconfirmed TB meningitis. MTBVAC was immunogenic at all 3 doses, inducing predominantly Th1-cytokine-expressing CD4 T cells, which peaked at Day 56. The 2.5 × 105 and 2.5 × 106 CFU MTBVAC doses induced similar response magnitudes and were more immunogenic than BCG. Day 56 IGRA conversion was observed in 61 (87.4%) infants receiving any MTBVAC dose, but only 28 (42.4%) remained positive by Day 365. Interpretation. MTBVAC appeared safe, well-tolerated, and immunogenic at doses between 2.5 × 104 and 2.5 × 106 CFU in South African infants. The 2.5 × 105 CFU MTBVAC dose, being less reactogenic and more immunogenic than BCG, was selected for a multi-centre, phase 3 trial. info:eu-repo/grantAgreement/EUR/EDCTP/RIA2016V-1637 info:eu-repo/semantics/openAccess by-nc https://creativecommons.org/licenses/by-nc/4.0/deed.es info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Rozot, Virginie Imbratta, Claire Geldenhuys, Hennie Mendelsohn, Simon C. Kany Luabeya, Angelique Kany Shenje, Justin Tredoux, Nicolette Fisher, Michelle Mulenga, Humphrey Bilek, Nicole Young, Carly Veldsman, Ashley Botes, Natasja Thole, Jelle Fritzell, Bernard Mukherjee, Rajat Jelsbak, Ingrid Murillo Rodriguez, Esteban Puentes, Eugenia Doce, Juana Marinova, Dessislava (orcid)0000-0001-8644-120X Gonzalo-Asensio, Jesús Universidad de Zaragoza (orcid)0000-0001-8841-6593 Aguilo, Nacho Universidad de Zaragoza (orcid)0000-0001-7897-9173 Martin, Carlos Universidad de Zaragoza (orcid)0000-0003-2993-5478 Scriba, Thomas J. Hatherill, Mark Abrahams, Charmaine Africa, Hadn Arendsen, Denis Barnard, Liezl Cloete, Yolundi Davids, Ilse Erasmus, Mzwandile Filander, Elizabeth Gregg, Yolande Herling, Roxane Jansen, Ruwiyda Jack, Lungisa Kelepu, Xoliswe Kyepa, Henriette Leopeng, Thelma Mabwe, Simbarahse Mactavie, Lauren Makhete, Lebohang Mangali, Sandisiwe Mouton, Angelique Nkambule, Hlengiwe Noble, Julia Nombida, Onke Nqakala, Nambitha Opperman, Fajwa Raphela, Rodney Rossouw, Susan Schoeman, Elisma Schreuder, Constance Steyn, Marcia Swanepoel, Liticia Toefy, Asma Tromp, Anele Tyambethu, Petrus Valley, Habibullah Van Rooyes, Johanna 1011 630 Universidad de Zaragoza Dpto. Microb.Ped.Radio.Sal.Pú. Área Microbiología 1011 566 Universidad de Zaragoza Dpto. Microb.Ped.Radio.Sal.Pú. Área Inmunología 114 (2025), 105628 [12 pp.] EBioMedicine EBioMedicine 2352-3964 1175535 http://zaguan.unizar.es/record/153114/files/texto_completo.pdf Versión publicada 2388489 http://zaguan.unizar.es/record/153114/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:153114 articulos driver 2025-10-17-14:22:36 ARTICLE