The Recombinant Bacille Calmette-Guérin Vaccine VPM1002: Ready for Clinical Efficacy Testing.
The Recombinant Bacille Calmette-Guérin Vaccine VPM1002: Ready for Clinical Efficacy Testing.
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重组卡介苗疫苗 VPM1002：准备进行临床功效测试。
DOI：
10.3389/fimmu.2017.01147
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发表时间：
2017
影响因子：
7.3
通讯作者：
Kaufmann SHE
中科院分区：
文献类型：
--
作者：
Nieuwenhuizen NE;Kulkarni PS;Shaligram U;Cotton MF;Rentsch CA;Eisele B;Grode L;Kaufmann SHE
唯一获得许可的结核病（TB）疫苗，卡介苗（BCG），可预防严重的肺外形式的TB，但对最流行的疾病形式肺结核几乎无效。BCG在Max Planck感染生物学研究所进行了遗传修饰，通过用来自单核细胞增生李斯特菌的溶血素编码基因替换尿素酶C编码基因来改善其免疫原性。李斯特菌溶血素在酸性pH下扰乱吞噬体膜。尿素酶C参与中和携带BCG的吞噬体。其消耗允许快速吞噬体酸化并促进吞噬溶酶体融合。因此，BCGΔureC：：hly（VPM 1002）促进细胞凋亡和自噬，并促进分枝杆菌抗原释放到胞质溶胶中。在临床前研究中，VPM 1002比BCG更有效和安全。该疫苗被许可给Vakzine Projekt Management，后来又被许可给印度血清研究所，世界上最大的疫苗生产商该疫苗已在德国和南非通过I期临床试验，证明了其在年轻成人中的安全性和免疫原性。它还在南非健康新生儿的IIa期随机临床试验中成功进行了测试，目前正在对艾滋病毒暴露和未暴露的新生儿进行IIb期研究。2017年将在印度开始一项II/III期临床试验，以评估对结核病复发的疗效。VPM 1002的目标适应症是新生儿免疫接种以预防结核病，以及成人暴露后免疫接种以预防结核病复发。此外，在非肌肉浸润性膀胱癌患者中进行的I期试验已经完成，II期试验正在进行中。本文介绍了VPM 1002从绘图板到临床评估的发展过程。
The only licensed vaccine against tuberculosis (TB), bacille Calmette–Guérin (BCG), protects against severe extrapulmonary forms of TB but is virtually ineffective against the most prevalent form of the disease, pulmonary TB. BCG was genetically modified at the Max Planck Institute for Infection Biology to improve its immunogenicity by replacing the urease C encoding gene with the listeriolysin encoding gene from Listeria monocytogenes. Listeriolysin perturbates the phagosomal membrane at acidic pH. Urease C is involved in neutralization of the phagosome harboring BCG. Its depletion allows for rapid phagosome acidification and promotes phagolysosome fusion. As a result, BCGΔureC::hly (VPM1002) promotes apoptosis and autophagy and facilitates release of mycobacterial antigens into the cytosol. In preclinical studies, VPM1002 has been far more efficacious and safer than BCG. The vaccine was licensed to Vakzine Projekt Management and later sublicensed to the Serum Institute of India Pvt. Ltd., the largest vaccine producer in the world. The vaccine has passed phase I clinical trials in Germany and South Africa, demonstrating its safety and immunogenicity in young adults. It was also successfully tested in a phase IIa randomized clinical trial in healthy South African newborns and is currently undergoing a phase IIb study in HIV exposed and unexposed newborns. A phase II/III clinical trial will commence in India in 2017 to assess efficacy against recurrence of TB. The target indications for VPM1002 are newborn immunization to prevent TB as well as post-exposure immunization in adults to prevent TB recurrence. In addition, a Phase I trial in non-muscle invasive bladder cancer patients has been completed, and phase II trials are ongoing. This review describes the development of VPM1002 from the drawing board to its clinical assessment.
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影响因子：
17.1
作者：
Biot, Claire;Rentsch, Cyrill A.;Albert, Matthew L.
通讯作者：
Albert, Matthew L.
影响因子：
5.5
作者：
Farinacci, Maura;Weber, Stephan;Kaufmann, Stefan H. E.
通讯作者：
Kaufmann, Stefan H. E.
影响因子：
--
作者：
Bekkering, Siroon;Blok, Bastiaan A.;Netea, Mihai G.
通讯作者：
Netea, Mihai G.
影响因子：
3.1
作者：
Fulton, SA;Reba, SM;Boom, WH
通讯作者：
Boom, WH
影响因子：
5.4
作者：
Dorhoi, Anca;Nouailles, Geraldine;Kaufmann, Stefan H. E.
通讯作者：
Kaufmann, Stefan H. E.