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M72/AS01E疫苗可有效预防成人结核病
作者:小柯机器人 发布时间:2019/11/3 22:54:33

 
葛兰素史克公司的Olivier Van Der Meeren等研究人员,分析了M72/AS01E疫苗预防结核病的试验结果。2019年10月29日,《新英格兰医学杂志》在线发表了这一成果。
 
M72/AS01E结核分枝杆菌候选疫苗试验的早期分析结果显示,该疫苗可为已感染的成人提供54.0%的保护,以预防活动性肺结核病,且没有明显的安全问题。
 
2014年8月至2015年11月,研究组在肯尼亚、南非和赞比亚的各中心招募18-50岁感染了结核分枝杆菌,但未发现活动性肺结核病的成年人。将这些参与者按1:1随机分组,分别接受两剂M72/AS01E疫苗或安慰剂,间隔1个月给药。
 
共有3573名参与者接受了至少一剂M72/AS01E或安慰剂,其中3330名接受了两剂。随访3年后,M72/AS01E组1626名参与者中有13名确诊HIV阴性的肺结核,安慰剂组1663名参与者中有26名,发病率分别为每100人年0.3和0.6。
 
第36个月的疫苗效力为49.7%。M72/AS01E组中,第一次给药后M72特异性抗体的浓度和M72特异性CD4+T细胞的频率均显著增加,并持续至整个随访期。两组中严重不良事件、潜在免疫介导疾病和死亡的发生率相差不大。
 
综上,对于感染结核分枝杆菌的成年人,接种M72/AS01E疫苗可引起免疫应答,并至少在3年内预防肺结核疾病的发展。
 
 
附:英文原文
 
Title:Final Analysis of a Trial of M72/AS01E Vaccine to Prevent Tuberculosis
 
Author:Dereck R. Tait, M.B., Ch.B., Mark Hatherill, M.D., Olivier Van Der Meeren, M.D., Ann M. Ginsberg, M.D., Ph.D., Elana Van Brakel, M.B., Ch.B., Bruno Salaun, Ph.D., Thomas J. Scriba, Ph.D., Elaine J. Akite, M.Sc., Helen M. Ayles, M.B., B.S., Ph.D., Anne Bollaerts, M.Sc., Marie-Ange Demoitié, M.Sc., Andreas Diacon, M.D., Ph.D., Thomas G. Evans, M.D., Paul Gillard, M.D., Elizabeth Hellström, M.B., Ch.B., James C. Innes, M.B., Ch.B., Maria Lempicki, M.Sc., Mookho Malahleha, M.B., Ch.B., M.P.H., Neil Martinson, M.B., Ch.B., M.P.H., Doris Mesia Vela, M.D., Monde Muyoyeta, M.B., Ch.B., Ph.D., Videlis Nduba, M.B., Ch.B., M.P.H., Thierry G. Pascal, Ph.D., Michele Tameris, M.B., Ch.B., Friedrich Thienemann, M.D., Robert J. Wilkinson, F.Med.Sci., and François Roman, M.D., Ph.D.
 
Issue&Volume:October 29, 2019
 
Abstract: 

BACKGROUND
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.

METHODS
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.

RESULTS
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.

CONCLUSIONS
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. 

DOI: 10.1056/NEJMoa1909953

Source:https://www.nejm.org/doi/full/10.1056/NEJMoa1909953

期刊信息

The New England Journal of Medicine:《新英格兰医学杂志》,创刊于1812年。隶属于麻省医学协会,最新IF:70.67
官方网址:http://www.nejm.org/
投稿链接:http://www.nejm.org/page/author-center/home