@article{VanDerMeeren2018,
abstract = {BACKGROUND A vaccine to interrupt the transmission of tuberculosis is needed. METHODS We conducted a randomized, double-blind, placebo-controlled, phase 2b trial of the M72/AS01E tuberculosis vaccine in Kenya, South Africa, and Zambia. Human immunodeficiency virus (HIV)-negative adults 18 to 50 years of age with latent M. tuberculosis infection (by interferon-$\gamma$ release assay) were randomly assigned (in a 1:1 ratio) to receive two doses of either M72/AS01E or placebo intramuscularly 1 month apart. Most participants had previously received the bacille Calmette-Gu{\'{e}}rin vaccine. We assessed the safety of M72/AS01E and its efficacy against progression to bacteriologically confirmed active pulmonary tuberculosis disease. Clinical suspicion of tuberculosis was confirmed with sputum by means of a polymerase-chain-reaction test, mycobacterial culture, or both. RESULTS We report the primary analysis (conducted after a mean of 2.3 years of follow-up) of the ongoing trial. A total of 1786 participants received M72/AS01E and 1787 received placebo, and 1623 and 1660 participants in the respective groups were included in the according-to-protocol efficacy cohort. A total of 10 participants in the M72/AS01E group met the primary case definition (bacteriologically confirmed active pulmonary tuberculosis, with confirmation before treatment), as compared with 22 participants in the placebo group (incidence, 0.3 cases vs. 0.6 cases per 100 person-years). The vaccine efficacy was 54.0{\%} (90{\%} confidence interval [CI], 13.9 to 75.4; 95{\%} CI, 2.9 to 78.2; P=0.04). Results for the total vaccinated efficacy cohort were similar (vaccine efficacy, 57.0{\%}; 90{\%} CI, 19.9 to 76.9; 95{\%} CI, 9.7 to 79.5; P=0.03). There were more unsolicited reports of adverse events in the M72/AS01E group (67.4{\%}) than in the placebo group (45.4{\%}) within 30 days after injection, with the difference attributed mainly to injection-site reactions and influenza-like symptoms. Serious adverse events, potential immune-mediated diseases, and deaths occurred with similar frequencies in the two groups. CONCLUSIONS M72/AS01E provided 54.0{\%} protection for M. tuberculosis-infected adults against active pulmonary tuberculosis disease, without evident safety concerns. (Funded by GlaxoSmithKline Biologicals and Aeras; ClinicalTrials.gov number, NCT01755598 .).},
author = {{Van Der Meeren}, Olivier and Hatherill, Mark and Nduba, Videlis and Wilkinson, Robert J and Muyoyeta, Monde and {Van Brakel}, Elana and Ayles, Helen M and Henostroza, German and Thienemann, Friedrich and Scriba, Thomas J and Diacon, Andreas H and Blatner, Gretta L and Demoiti{\'{e}}, Marie-Ange and Tameris, Michele and Malahleha, Mookho and Innes, James C and Hellstr{\"{o}}m, Elizabeth and Martinson, Neil and Singh, Tina and Akite, Elaine J and {Khatoon Azam}, Aisha and Bollaerts, Anne and Ginsberg, Ann M and Evans, Thomas G and Gillard, Paul and Tait, Dereck R},
doi = {10.1056/NEJMoa1803484},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Van Der Meeren et al. - 2018 - Phase 2b controlled trial of M72AS01E vaccine to prevent tuberculosis.pdf:pdf},
isbn = {1533-4406 0028-4793},
issn = {0028-4793},
journal = {New England Journal of Medicine},
keywords = {OA,fund{\_}ack,original},
mendeley-tags = {OA,fund{\_}ack,original},
month = {sep},
pages = {1621--1634},
pmid = {30280651},
publisher = {Massachusetts Medical Society},
title = {{Phase 2b controlled trial of M72/AS01[E] vaccine to prevent tuberculosis}},
url = {http://www.nejm.org/doi/10.1056/NEJMoa1803484},
volume = {379},
year = {2018}
}

{"_id":"5XPwCnCWGSR35w9fL","bibbaseid":"vandermeeren-hatherill-nduba-wilkinson-muyoyeta-vanbrakel-ayles-henostroza-etal-phase2bcontrolledtrialofm72as01evaccinetopreventtuberculosis-2018","author_short":["Van Der Meeren, O.","Hatherill, M.","Nduba, V.","Wilkinson, R. J","Muyoyeta, M.","Van Brakel, E.","Ayles, H. M","Henostroza, G.","Thienemann, F.","Scriba, T. J","Diacon, A. H","Blatner, G. L","Demoitié, M.","Tameris, M.","Malahleha, M.","Innes, J. C","Hellström, E.","Martinson, N.","Singh, T.","Akite, E. J","Khatoon Azam, A.","Bollaerts, A.","Ginsberg, A. M","Evans, T. G","Gillard, P.","Tait, D. R"],"bibdata":{"bibtype":"article","type":"article","abstract":"BACKGROUND A vaccine to interrupt the transmission of tuberculosis is needed. METHODS We conducted a randomized, double-blind, placebo-controlled, phase 2b trial of the M72/AS01E tuberculosis vaccine in Kenya, South Africa, and Zambia. Human immunodeficiency virus (HIV)-negative adults 18 to 50 years of age with latent M. tuberculosis infection (by interferon-$γ$ release assay) were randomly assigned (in a 1:1 ratio) to receive two doses of either M72/AS01E or placebo intramuscularly 1 month apart. Most participants had previously received the bacille Calmette-Guérin vaccine. We assessed the safety of M72/AS01E and its efficacy against progression to bacteriologically confirmed active pulmonary tuberculosis disease. Clinical suspicion of tuberculosis was confirmed with sputum by means of a polymerase-chain-reaction test, mycobacterial culture, or both. RESULTS We report the primary analysis (conducted after a mean of 2.3 years of follow-up) of the ongoing trial. A total of 1786 participants received M72/AS01E and 1787 received placebo, and 1623 and 1660 participants in the respective groups were included in the according-to-protocol efficacy cohort. A total of 10 participants in the M72/AS01E group met the primary case definition (bacteriologically confirmed active pulmonary tuberculosis, with confirmation before treatment), as compared with 22 participants in the placebo group (incidence, 0.3 cases vs. 0.6 cases per 100 person-years). The vaccine efficacy was 54.0% (90% confidence interval [CI], 13.9 to 75.4; 95% CI, 2.9 to 78.2; P=0.04). Results for the total vaccinated efficacy cohort were similar (vaccine efficacy, 57.0%; 90% CI, 19.9 to 76.9; 95% CI, 9.7 to 79.5; P=0.03). There were more unsolicited reports of adverse events in the M72/AS01E group (67.4%) than in the placebo group (45.4%) within 30 days after injection, with the difference attributed mainly to injection-site reactions and influenza-like symptoms. Serious adverse events, potential immune-mediated diseases, and deaths occurred with similar frequencies in the two groups. CONCLUSIONS M72/AS01E provided 54.0% protection for M. tuberculosis-infected adults against active pulmonary tuberculosis disease, without evident safety concerns. (Funded by GlaxoSmithKline Biologicals and Aeras; ClinicalTrials.gov number, NCT01755598 .).","author":[{"propositions":[],"lastnames":["Van Der Meeren"],"firstnames":["Olivier"],"suffixes":[]},{"propositions":[],"lastnames":["Hatherill"],"firstnames":["Mark"],"suffixes":[]},{"propositions":[],"lastnames":["Nduba"],"firstnames":["Videlis"],"suffixes":[]},{"propositions":[],"lastnames":["Wilkinson"],"firstnames":["Robert","J"],"suffixes":[]},{"propositions":[],"lastnames":["Muyoyeta"],"firstnames":["Monde"],"suffixes":[]},{"propositions":[],"lastnames":["Van Brakel"],"firstnames":["Elana"],"suffixes":[]},{"propositions":[],"lastnames":["Ayles"],"firstnames":["Helen","M"],"suffixes":[]},{"propositions":[],"lastnames":["Henostroza"],"firstnames":["German"],"suffixes":[]},{"propositions":[],"lastnames":["Thienemann"],"firstnames":["Friedrich"],"suffixes":[]},{"propositions":[],"lastnames":["Scriba"],"firstnames":["Thomas","J"],"suffixes":[]},{"propositions":[],"lastnames":["Diacon"],"firstnames":["Andreas","H"],"suffixes":[]},{"propositions":[],"lastnames":["Blatner"],"firstnames":["Gretta","L"],"suffixes":[]},{"propositions":[],"lastnames":["Demoitié"],"firstnames":["Marie-Ange"],"suffixes":[]},{"propositions":[],"lastnames":["Tameris"],"firstnames":["Michele"],"suffixes":[]},{"propositions":[],"lastnames":["Malahleha"],"firstnames":["Mookho"],"suffixes":[]},{"propositions":[],"lastnames":["Innes"],"firstnames":["James","C"],"suffixes":[]},{"propositions":[],"lastnames":["Hellström"],"firstnames":["Elizabeth"],"suffixes":[]},{"propositions":[],"lastnames":["Martinson"],"firstnames":["Neil"],"suffixes":[]},{"propositions":[],"lastnames":["Singh"],"firstnames":["Tina"],"suffixes":[]},{"propositions":[],"lastnames":["Akite"],"firstnames":["Elaine","J"],"suffixes":[]},{"propositions":[],"lastnames":["Khatoon Azam"],"firstnames":["Aisha"],"suffixes":[]},{"propositions":[],"lastnames":["Bollaerts"],"firstnames":["Anne"],"suffixes":[]},{"propositions":[],"lastnames":["Ginsberg"],"firstnames":["Ann","M"],"suffixes":[]},{"propositions":[],"lastnames":["Evans"],"firstnames":["Thomas","G"],"suffixes":[]},{"propositions":[],"lastnames":["Gillard"],"firstnames":["Paul"],"suffixes":[]},{"propositions":[],"lastnames":["Tait"],"firstnames":["Dereck","R"],"suffixes":[]}],"doi":"10.1056/NEJMoa1803484","file":":C$\\$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Van Der Meeren et al. - 2018 - Phase 2b controlled trial of M72AS01E vaccine to prevent tuberculosis.pdf:pdf","isbn":"1533-4406 0028-4793","issn":"0028-4793","journal":"New England Journal of Medicine","keywords":"OA,fund_ack,original","mendeley-tags":"OA,fund_ack,original","month":"sep","pages":"1621–1634","pmid":"30280651","publisher":"Massachusetts Medical Society","title":"Phase 2b controlled trial of M72/AS01[E] vaccine to prevent tuberculosis","url":"http://www.nejm.org/doi/10.1056/NEJMoa1803484","volume":"379","year":"2018","bibtex":"@article{VanDerMeeren2018,\r\nabstract = {BACKGROUND A vaccine to interrupt the transmission of tuberculosis is needed. METHODS We conducted a randomized, double-blind, placebo-controlled, phase 2b trial of the M72/AS01E tuberculosis vaccine in Kenya, South Africa, and Zambia. Human immunodeficiency virus (HIV)-negative adults 18 to 50 years of age with latent M. tuberculosis infection (by interferon-$\\gamma$ release assay) were randomly assigned (in a 1:1 ratio) to receive two doses of either M72/AS01E or placebo intramuscularly 1 month apart. Most participants had previously received the bacille Calmette-Gu{\\'{e}}rin vaccine. We assessed the safety of M72/AS01E and its efficacy against progression to bacteriologically confirmed active pulmonary tuberculosis disease. Clinical suspicion of tuberculosis was confirmed with sputum by means of a polymerase-chain-reaction test, mycobacterial culture, or both. RESULTS We report the primary analysis (conducted after a mean of 2.3 years of follow-up) of the ongoing trial. A total of 1786 participants received M72/AS01E and 1787 received placebo, and 1623 and 1660 participants in the respective groups were included in the according-to-protocol efficacy cohort. A total of 10 participants in the M72/AS01E group met the primary case definition (bacteriologically confirmed active pulmonary tuberculosis, with confirmation before treatment), as compared with 22 participants in the placebo group (incidence, 0.3 cases vs. 0.6 cases per 100 person-years). The vaccine efficacy was 54.0{\\%} (90{\\%} confidence interval [CI], 13.9 to 75.4; 95{\\%} CI, 2.9 to 78.2; P=0.04). Results for the total vaccinated efficacy cohort were similar (vaccine efficacy, 57.0{\\%}; 90{\\%} CI, 19.9 to 76.9; 95{\\%} CI, 9.7 to 79.5; P=0.03). There were more unsolicited reports of adverse events in the M72/AS01E group (67.4{\\%}) than in the placebo group (45.4{\\%}) within 30 days after injection, with the difference attributed mainly to injection-site reactions and influenza-like symptoms. Serious adverse events, potential immune-mediated diseases, and deaths occurred with similar frequencies in the two groups. CONCLUSIONS M72/AS01E provided 54.0{\\%} protection for M. tuberculosis-infected adults against active pulmonary tuberculosis disease, without evident safety concerns. (Funded by GlaxoSmithKline Biologicals and Aeras; ClinicalTrials.gov number, NCT01755598 .).},\r\nauthor = {{Van Der Meeren}, Olivier and Hatherill, Mark and Nduba, Videlis and Wilkinson, Robert J and Muyoyeta, Monde and {Van Brakel}, Elana and Ayles, Helen M and Henostroza, German and Thienemann, Friedrich and Scriba, Thomas J and Diacon, Andreas H and Blatner, Gretta L and Demoiti{\\'{e}}, Marie-Ange and Tameris, Michele and Malahleha, Mookho and Innes, James C and Hellstr{\\\"{o}}m, Elizabeth and Martinson, Neil and Singh, Tina and Akite, Elaine J and {Khatoon Azam}, Aisha and Bollaerts, Anne and Ginsberg, Ann M and Evans, Thomas G and Gillard, Paul and Tait, Dereck R},\r\ndoi = {10.1056/NEJMoa1803484},\r\nfile = {:C$\\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Van Der Meeren et al. - 2018 - Phase 2b controlled trial of M72AS01E vaccine to prevent tuberculosis.pdf:pdf},\r\nisbn = {1533-4406 0028-4793},\r\nissn = {0028-4793},\r\njournal = {New England Journal of Medicine},\r\nkeywords = {OA,fund{\\_}ack,original},\r\nmendeley-tags = {OA,fund{\\_}ack,original},\r\nmonth = {sep},\r\npages = {1621--1634},\r\npmid = {30280651},\r\npublisher = {Massachusetts Medical Society},\r\ntitle = {{Phase 2b controlled trial of M72/AS01[E] vaccine to prevent tuberculosis}},\r\nurl = {http://www.nejm.org/doi/10.1056/NEJMoa1803484},\r\nvolume = {379},\r\nyear = {2018}\r\n}\r\n","author_short":["Van Der Meeren, O.","Hatherill, M.","Nduba, V.","Wilkinson, R. 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