一项在动物中所做的新的研究报告说，一种新的结核病疫苗可提高一种孩提时接种的结核病疫苗的有效性，并能保护机体不受抗药结核菌的侵害。抗药结核菌是一个全世界范围内的日益严重的问题。

人们正在研发这种疫苗以期在人类中进行临床测试；如果成功的话，它将保护人们免受日益增多的抗药结核菌的感染，该抗药菌所致的疾病被许多人所认为一种全球性公共卫生所面临的危机。 孩提时接种的结核菌疫苗（即：卡介苗）的功效会随着时间而减弱，因此，人们不能指望该疫苗来预防成年人所罹患的结核病。 现在，Sylvie Bertholet及其同事介绍了一种由结核分枝杆菌的组合蛋白所制备的疫苗；他们证明，这种新的疫苗可显著地加强孩提时结核疫苗所产生的保护机体的能力，此外，该新疫苗还可保护机体免受抗药结核菌的侵害。

该疫苗是由4个蛋白所融合成的一个单一分子所组成的。 这里所选的每一种蛋白都是因为其具有保护实验动物模型免于罹患结核病的能力。 将不同的蛋白组合在一起对疫苗是重要的，因为结核菌有许多不同的类型，而没有一种单一的蛋白可有效地抵御所有的结核菌株。 另外，没有2个人 情况是完全相同的；每个人对每个蛋白的反应都不一样。 将与存在于天然结核菌中的类似蛋白组合起来可能会增加疫苗的功效。 研究人员在小鼠、豚鼠和猴子中测试了这种新的疫苗；他们发现，该4种蛋白所组成的疫苗可激发动物体内的关键性的免役细胞反应。 例如，在吸入被结核菌污染的空气的小鼠中，该疫苗可保护小鼠随后发生的结核菌感染，甚至还可保护其免受一种已知对数个常用抗结核菌药物有抵抗力的结核菌株的感染。 为了模拟在人体中所见到的卡介苗的微弱的保护能力，文章的作者还在豚鼠体内注射了短期的卡介苗疫苗。 在接受该治疗的几个月之后，这种由4种蛋白所组成的疫苗可保护豚鼠免受结核菌的感染，从而有效地提高了卡介苗所赋予的免役能力。

英文摘要：

Sci Transl Med  DOI:10.1126/scitranslmed.3001094

A Defined Tuberculosis Vaccine Candidate Boosts BCG and Protects Against Multidrug-Resistant Mycobacterium tuberculosis
Sylvie Bertholet1,*, Gregory C. Ireton1, Diane J. Ordway2, Hillarie Plessner Windish1, Samuel O. Pine1, Maria Kahn1, Tony Phan1, Ian M. Orme2, Thomas S. Vedvick1, Susan L. Baldwin1, Rhea N. Coler1,?? and Steven G. Reed1,?

Despite the widespread use of the childhood vaccine against tuberculosis (TB), Mycobacterium bovis bacillus Calmette-Guérin (BCG), the disease remains a serious global health problem. A successful vaccine against TB that replaces or boosts BCG would include antigens that induce or recall the appropriate T cell responses. Four Mycobacterium tuberculosis (Mtb) antigens—including members of the virulence factor families PE/PPE and EsX or antigens associated with latency—were produced as a single recombinant fusion protein (ID93). When administered together with the adjuvant GLA-SE, a stable oil-in-water nanoemulsion, the fusion protein was immunogenic in mice, guinea pigs, and cynomolgus monkeys. In mice, this fusion protein–adjuvant combination induced polyfunctional CD4 T helper 1 cell responses characterized by antigen-specific interferon-γ, tumor necrosis factor, and interleukin-2, as well as a reduction in the number of bacteria in the lungs of animals after they were subsequently infected with virulent or multidrug-resistant Mtb strains. Furthermore, boosting BCG-vaccinated guinea pigs with fusion peptide–adjuvant resulted in reduced pathology and fewer bacilli, and prevented the death of animals challenged with virulent Mtb. Finally, the fusion protein elicited polyfunctional effector CD4 and CD8 T cell responses in BCG-vaccinated or Mtb-exposed human peripheral blood mononuclear cells. This study establishes that the protein subunit vaccine consisting of the fusion protein and adjuvant protects against TB and drug-resistant TB in animals and is a candidate for boosting the protective efficacy of the childhood BCG vaccine in humans.