Safety and immunogenicity of candidate vaccine M72/AS01E in adolescents in a TB endemic setting.
Safety and immunogenicity of candidate vaccine M72/AS01E in adolescents in a TB endemic setting.
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DOI：
10.1016/j.vaccine.2015.05.088
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发表时间：
2015-07-31
期刊：
影响因子：
5.5
通讯作者：
Scriba TJ
中科院分区：
文献类型：
--
作者：
Penn-Nicholson A;Geldenhuys H;Burny W;van der Most R;Day CL;Jongert E;Moris P;Hatherill M;Ofori-Anyinam O;Hanekom W;Vaccine Study Team;Bollaerts A;Demoitie MA;Kany Luabeya AK;De Ruymaeker E;Tameris M;Lapierre D;Scriba TJ
预防结核病（TB）的疫苗接种，尤其是在青少年中进行接种，将对全球结核病疫情产生最大影响。在一个结核病流行地区，对健康的、HIV阴性的青少年评估了候选疫苗M72/AS01E的安全性、反应原性和免疫原性，无论其结核分枝杆菌（M.tb）感染状况如何。
在一项II期双盲随机对照研究（NCT00950612）中，参与者肌肉注射两剂M72/AS01E或安慰剂，间隔一个月。在接种疫苗后对参与者进行了6个月的随访。通过流式细胞术对T细胞和NK细胞进行细胞内细胞因子染色分析来评估M72特异性免疫原性。
未记录到严重不良事件。M72/AS01E诱导了强烈的T细胞和抗体反应，包括抗原依赖性NK细胞产生干扰素 - γ。接种疫苗6个月后，CD4和CD8 T细胞反应持续存在。无论M.tb感染状况如何，接种疫苗诱导了高频率的表达多种Th1细胞因子组合的M72特异性CD4 T细胞以及低水平的IL - 17。我们观察到在M.tb感染的参与者中免疫反应迅速增强，这表明自然感染对疫苗接种起到了启动作用。
M72/AS01E在结核病高负担地区的青少年中具有临床可接受的安全性和免疫原性特征，这支持开展有效性试验。
Vaccination that prevents tuberculosis (TB) disease, particularly in adolescents, would have the greatest impact on the global TB epidemic. Safety, reactogenicity and immunogenicity of the vaccine candidate M72/AS01E was evaluated in healthy, HIV-negative adolescents in a TB endemic region, regardless of Mycobacterium tuberculosis (M.tb) infection status. In a phase II, double-blind randomized, controlled study (NCT00950612), two doses of M72/AS01E or placebo were administered intramuscularly, one month apart. Participants were followed-up post-vaccination, for 6 months. M72-specific immunogenicity was evaluated by intracellular cytokine staining analysis of T cells and NK cells by flow cytometry. No serious adverse events were recorded. M72/AS01E induced robust T cell and antibody responses, including antigen-dependent NK cell IFN-γ production. CD4 and CD8 T cell responses were sustained at 6 months post vaccination. Irrespective of M.tb infection status, vaccination induced a high frequency of M72-specific CD4 T cells expressing multiple combinations of Th1 cytokines, and low level IL-17. We observed rapid boosting of immune responses in M.tb-infected participants, suggesting natural infection acts as a prime to vaccination. The clinically acceptable safety and immunogenicity profile of M72/AS01E in adolescents living in an area with high TB burden support the move to efficacy trials.
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DOI：
10.4049/jimmunol.1102710
发表时间：
2012-05-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Horowitz A;Hafalla JC;King E;Lusingu J;Dekker D;Leach A;Moris P;Cohen J;Vekemans J;Villafana T;Corran PH;Bejon P;Drakeley CJ;von Seidlein L;Riley EM
通讯作者：
Riley EM
DOI：
10.1164/rccm.201003-0334oc
发表时间：
2010-10-15
影响因子：
24.7
作者：
Kagina, Benjamin M. N.;Abel, Brian;Hanekom, Willem A.
通讯作者：
Hanekom, Willem A.
影响因子：
158.5
作者：
Keane, J;Gershon, S;Braun, MM
通讯作者：
Braun, MM
DOI：
10.1084/jem.20100090
发表时间：
2010-12-20
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Geldmacher C;Ngwenyama N;Schuetz A;Petrovas C;Reither K;Heeregrave EJ;Casazza JP;Ambrozak DR;Louder M;Ampofo W;Pollakis G;Hill B;Sanga E;Saathoff E;Maboko L;Roederer M;Paxton WA;Hoelscher M;Koup RA
通讯作者：
Koup RA
影响因子：
4.4
作者：
Horowitz, Amir;Behrens, Ron H.;Riley, Eleanor M.
通讯作者：
Riley, Eleanor M.