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N Engl J Med. 2019 Dec 19;381(25):2429-2439. doi: 10.1056/NEJMoa1909953. Epub 2019 Oct 29.

Final Analysis of a Trial of M72/AS01E Vaccine to Prevent Tuberculosis.

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From the International AIDS Vaccine Initiative (IAVI) (D.R.T.), the South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology (M.H., T.J.S., M.T.), and the Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine (F.T., R.J.W.), University of Cape Town, TASK Applied Science (E.V.B., A.D.), and Stellenbosch University (A.D.), Cape Town, the Be Part Yoluntu Centre, Paarl (E.H.), the Aurum Institute, Klerksdorp Research Centre, Klerksdorp (J.C.I.), the Aurum Institute, Tembisa Research Centre, Tembisa (J.C.I.), Setshaba Research Centre, Pretoria (M. Malahleha), and the Perinatal HIV Research Unit, Chris Hani Baragwanath Hospital, South African Medical Research Council Collaborating Centre for HIV/AIDS and TB, and National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research, University of the Witwatersrand, Johannesburg (N.M.) - all in South Africa; GlaxoSmithKline, Wavre, and GlaxoSmithKline, Rixensart - both in Belgium (O.V.D.M., B.S., E.J.A., A.B., M.-A.D., P.G., D.M.V., T.G.P., F.R.); the IAVI, New York (A.M.G., T.G.E., M.L.); Zambart, University of Zambia (H.M.A.), and the Centre for Infectious Disease Research in Zambia (M. Muyoyeta) - both in Lusaka; the London School of Hygiene and Tropical Medicine (H.M.A.) and Francis Crick Institute and the Department of Medicine, Imperial College London (R.J.W.) - all in London; Johns Hopkins University Center for Tuberculosis Research, Baltimore (N.M.); the Kenya Medical Research Institute Centre for Respiratory Diseases Research, Nairobi (V.N.); and the Department of Internal Medicine, University Hospital of Zurich, Zurich, Switzerland (F.T.).



Results of an earlier analysis of a trial of the M72/AS01E candidate vaccine against Mycobacterium tuberculosis showed that in infected adults, the vaccine provided 54.0% protection against active pulmonary tuberculosis disease, without evident safety concerns. We now report the results of the 3-year final analysis of efficacy, safety, and immunogenicity.


From August 2014 through November 2015, we enrolled adults 18 to 50 years of age with M. tuberculosis infection (defined by positive results on interferon-γ release assay) without evidence of active tuberculosis disease at centers in Kenya, South Africa, and Zambia. Participants were randomly assigned in a 1:1 ratio to receive two doses of either M72/AS01E or placebo, administered 1 month apart. The primary objective was to evaluate the efficacy of M72/AS01E to prevent active pulmonary tuberculosis disease according to the first case definition (bacteriologically confirmed pulmonary tuberculosis not associated with human immunodeficiency virus infection). Participants were followed for 3 years after the second dose. Participants with clinical suspicion of tuberculosis provided sputum samples for polymerase-chain-reaction assay, mycobacterial culture, or both. Humoral and cell-mediated immune responses were evaluated until month 36 in a subgroup of 300 participants. Safety was assessed in all participants who received at least one dose of M72/AS01E or placebo.


A total of 3575 participants underwent randomization, of whom 3573 received at least one dose of M72/AS01E or placebo, and 3330 received both planned doses. Among the 3289 participants in the according-to-protocol efficacy cohort, 13 of the 1626 participants in the M72/AS01E group, as compared with 26 of the 1663 participants in the placebo group, had cases of tuberculosis that met the first case definition (incidence, 0.3 vs. 0.6 cases per 100 person-years). The vaccine efficacy at month 36 was 49.7% (90% confidence interval [CI], 12.1 to 71.2; 95% CI, 2.1 to 74.2). Among participants in the M72/AS01E group, the concentrations of M72-specific antibodies and the frequencies of M72-specific CD4+ T cells increased after the first dose and were sustained throughout the follow-up period. Serious adverse events, potential immune-mediated diseases, and deaths occurred with similar frequencies in the two groups.


Among adults infected with M. tuberculosis, vaccination with M72/AS01E elicited an immune response and provided protection against progression to pulmonary tuberculosis disease for at least 3 years. (Funded by GlaxoSmithKline Biologicals and Aeras; number, NCT01755598.).

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