Safety and immunogenicity of the M72/AS01E candidate tuberculosis vaccine in adults with tuberculosis: A phase II randomised study
Safety and immunogenicity of the M72/AS01E candidate tuberculosis vaccine in adults with tuberculosis: A phase II randomised study
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DOI：
10.1016/j.tube.2016.07.005
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发表时间：
2016-09-01
期刊：
影响因子：
3.2
通讯作者：
Castro, Marcela
中科院分区：
文献类型：
--
作者：
Gillard, Paul;Yang, Pan-Chyr;Castro, Marcela
先前的研究表明，M72/AS01(E)候选结核疫苗具有免疫原性，在健康和结核分枝杆菌感染的成年人中具有临床可接受的安全性。这项II期、观察者盲、随机化研究比较了M72/AS01(E)在3个队列中的安全性、反应原性和免疫原性：初患结核病的成年人（n = 80）、以前接受过结核病治疗的成年人（n = 49）和已经完成结核病强化治疗阶段的成年人（n = 13）。在每个队列中，18-59岁的成年人被随机分配（1:1）接受两剂M72/AS01(E) （n = 71）或安慰剂（n = 71），并随访至剂量2后6个月。安全性和反应原性评估是主要目标。由于在接受结核病治疗的M72/AS01(E)疫苗接种的成人中，大注射部位红肿反应的发生率很高，因此该研究的招募工作过早结束。除了一例可能与疫苗相关的严重不良事件（M72/AS01(E)结核治疗参与者的过敏反应）外，未观察到其他临床相关的不良事件。在每个队列中，接种m72 /AS01(E)疫苗后，观察到稳健和持续的m72特异性体液和多功能CD4(+) t细胞介导的免疫应答。总之，M72/AS01(E)疫苗在曾经或正在接受结核病治疗的成人中具有免疫原性，但需要进一步分析来解释在正在接受结核病治疗的成人中较高的局部反应原性。(C) 2016葛兰素史克生物制品有限公司Elsevier Ltd.出版。
Previous studies have shown that the M72/AS01(E) candidate tuberculosis vaccine is immunogenic with a clinically acceptable safety profile in healthy and Mycobacterium tuberculosis-infected adults. This phase II, observer-blind, randomised study compared the safety, reactogenicity, and immunogenicity of M72/AS01(E) in 3 cohorts: tuberculosis-naive adults (n = 80), adults previously treated for tuberculosis (n = 49), and adults who have completed the intensive phase of tuberculosis treatment (n = 13). In each cohort, 18-59-year-old adults were randomised (1: 1) to receive two doses of M72/AS01(E) (n = 71) or placebo (n = 71) and followed-up until six months post-dose 2. Safety and reactogenicity were assessed as primary objective.Recruitment in the study ended prematurely because of a high incidence of large injection site redness/swelling reactions in M72/AS01(E)-vaccinated adults undergoing tuberculosis treatment. No additional clinically relevant adverse events were observed, except one possibly vaccine-related serious adverse event (hypersensitivity in a tuberculosis-treated- M72/AS01(E) participant). Robust and persistent M72-specific humoral and polyfunctional CD4(+) T-cell-mediated immune responses were observed postM72/AS01(E) vaccination in each cohort. In conclusion, the M72/AS01(E) vaccine was immunogenic in adults previously or currently treated for tuberculosis, but further analyses are needed to explain the high local reactogenicity in adults undergoing tuberculosis treatment. (C) 2016 GlaxoSmithKline Biologicals SA. Published by Elsevier Ltd.