000153114 001__ 153114
000153114 005__ 20250410160822.0
000153114 0247_ $$2doi$$a10.1016/j.ebiom.2025.105628
000153114 0248_ $$2sideral$$a143585
000153114 037__ $$aART-2025-143585
000153114 041__ $$aeng
000153114 100__ $$aTameris, Michele
000153114 245__ $$aSafety, reactogenicity, and immunogenicity of MTBVAC in infants: a phase 2a randomised, double-blind, dose-defining trial in a TB endemic setting
000153114 260__ $$c2025
000153114 5060_ $$aAccess copy available to the general public$$fUnrestricted
000153114 5203_ $$aSafer 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.
000153114 536__ $$9info:eu-repo/grantAgreement/EUR/EDCTP/RIA2016V-1637
000153114 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc$$uhttp://creativecommons.org/licenses/by-nc/3.0/es/
000153114 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000153114 700__ $$aRozot, Virginie
000153114 700__ $$aImbratta, Claire
000153114 700__ $$aGeldenhuys, Hennie
000153114 700__ $$aMendelsohn, Simon C.
000153114 700__ $$aKany Luabeya, Angelique Kany
000153114 700__ $$aShenje, Justin
000153114 700__ $$aTredoux, Nicolette
000153114 700__ $$aFisher, Michelle
000153114 700__ $$aMulenga, Humphrey
000153114 700__ $$aBilek, Nicole
000153114 700__ $$aYoung, Carly
000153114 700__ $$aVeldsman, Ashley
000153114 700__ $$aBotes, Natasja
000153114 700__ $$aThole, Jelle
000153114 700__ $$aFritzell, Bernard
000153114 700__ $$aMukherjee, Rajat
000153114 700__ $$aJelsbak, Ingrid Murillo
000153114 700__ $$aRodriguez, Esteban
000153114 700__ $$aPuentes, Eugenia
000153114 700__ $$aDoce, Juana
000153114 700__ $$0(orcid)0000-0001-8644-120X$$aMarinova, Dessislava
000153114 700__ $$0(orcid)0000-0001-8841-6593$$aGonzalo-Asensio, Jesús$$uUniversidad de Zaragoza
000153114 700__ $$0(orcid)0000-0001-7897-9173$$aAguilo, Nacho$$uUniversidad de Zaragoza
000153114 700__ $$0(orcid)0000-0003-2993-5478$$aMartin, Carlos$$uUniversidad de Zaragoza
000153114 700__ $$aScriba, Thomas J.
000153114 700__ $$aHatherill, Mark
000153114 700__ $$aAbrahams, Charmaine
000153114 700__ $$aAfrica, Hadn
000153114 700__ $$aArendsen, Denis
000153114 700__ $$aBarnard, Liezl
000153114 700__ $$aCloete, Yolundi
000153114 700__ $$aDavids, Ilse
000153114 700__ $$aErasmus, Mzwandile
000153114 700__ $$aFilander, Elizabeth
000153114 700__ $$aGregg, Yolande
000153114 700__ $$aHerling, Roxane
000153114 700__ $$aJansen, Ruwiyda
000153114 700__ $$aJack, Lungisa
000153114 700__ $$aKelepu, Xoliswe
000153114 700__ $$aKyepa, Henriette
000153114 700__ $$aLeopeng, Thelma
000153114 700__ $$aMabwe, Simbarahse
000153114 700__ $$aMactavie, Lauren
000153114 700__ $$aMakhete, Lebohang
000153114 700__ $$aMangali, Sandisiwe
000153114 700__ $$aMouton, Angelique
000153114 700__ $$aNkambule, Hlengiwe
000153114 700__ $$aNoble, Julia
000153114 700__ $$aNombida, Onke
000153114 700__ $$aNqakala, Nambitha
000153114 700__ $$aOpperman, Fajwa
000153114 700__ $$aRaphela, Rodney
000153114 700__ $$aRossouw, Susan
000153114 700__ $$aSchoeman, Elisma
000153114 700__ $$aSchreuder, Constance
000153114 700__ $$aSteyn, Marcia
000153114 700__ $$aSwanepoel, Liticia
000153114 700__ $$aToefy, Asma
000153114 700__ $$aTromp, Anele
000153114 700__ $$aTyambethu, Petrus
000153114 700__ $$aValley, Habibullah
000153114 700__ $$aVan Rooyes, Johanna
000153114 7102_ $$11011$$2630$$aUniversidad de Zaragoza$$bDpto. Microb.Ped.Radio.Sal.Pú.$$cÁrea Microbiología
000153114 7102_ $$11011$$2566$$aUniversidad de Zaragoza$$bDpto. Microb.Ped.Radio.Sal.Pú.$$cÁrea Inmunología
000153114 773__ $$g114 (2025), 105628 [12 pp.]$$pEBioMedicine$$tEBioMedicine$$x2352-3964
000153114 8564_ $$s1175535$$uhttps://zaguan.unizar.es/record/153114/files/texto_completo.pdf$$yVersión publicada
000153114 8564_ $$s2388489$$uhttps://zaguan.unizar.es/record/153114/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000153114 909CO $$ooai:zaguan.unizar.es:153114$$particulos$$pdriver
000153114 951__ $$a2025-04-10-14:05:03
000153114 980__ $$aARTICLE