Safety and immunogenicity of investigational tuberculosis vaccine M72/AS01E–4 in people living with HIV in South Africa: an observer-blinded, randomised, controlled, phase 2 trial

作者：Alemnew F. Dagnew, Ling Han, Kogieleum Naidoo, Lee Fairlie, James C. Innes, Keren Middelkoop, Michèle Tameris, Robert J. Wilkinson, Jintanat Ananworanich, Daniel Bower, Lisa Schlehuber, Nicole Frahm, Ahu ÇINAR, Michael W. Dunne, Alexander C. Schmidt · 发表于：The Lancet HIV · 年份：2025 · DOI：10.1016/s2352-3018(25)00124-9 · 被引用次数：13 · 研究领域：Tuberculosis Research and Epidemiology、Immune responses and vaccinations、HIV Research and Treatment

Background M72/AS01 E–4 is a recombinant fusion protein vaccine candidate derived from two Mycobacterium tuberculosis antigens ( Mtb 32A and Mtb 39A) and AS01 E–4 adjuvant. We evaluated safety and immunogenicity of M72/AS01 E–4 in people living with HIV in South Africa. Methods In this observer-blinded, randomised, controlled, phase 2 trial, participants aged 16–35 years with well controlled HIV were enrolled from urban, semi-urban, and semi-rural settings in South Africa, including sites with high tuberculosis and HIV prevalence, as well as agricultural and mining communities. Participants were randomly assigned (1:1), stratified by site and interferon-gamma release assay (IGRA) status, to receive two intramuscular doses of M72/AS01 E–4 or placebo. Eligibility criteria included antiretroviral therapy for at least 3 months, HIV viral load of less than 200 copies per mL, CD4 counts of 200 cells per μL or higher, and previous completion of tuberculosis preventive therapy and no tuberculosis history. The sponsor and its delegates, the laboratory team, investigators, site staff, and participants were blinded to randomisation, whereas an unblinded pharmacist who was not involved in trial procedures prepared placebo and reconstituted M72/AS01 E-4 in unit-dose syringes covered with a blinding label. All participants who received at least one dose of either M72/AS01 E–4 or placebo were included in the safety population for safety analyses. Immunogenicity analyses were conducted using...