Locht C, Rouanet C
Inserm 1019, centre d'infection et immunité de Lille, CNRS UMR9204, université Lille Nord de France, institut Pasteur de Lille, 1, rue du Professeur-Calmette, 59019 Lille cedex, France.
Arch Pediatr. 2011 Sep;18(9):1023-7. doi: 10.1016/j.arcped.2011.05.003. Epub 2011 Jun 14.
Today, only one type of vaccine is available to protect against tuberculosis. This vaccine, called Bacille Calmette-Guérin (BCG) was developed approximately 100 years ago and has been administered at least 3 billion times. Initial multicenter studies have indicated an up to 93% efficacy against childhood tuberculosis mortality. Subsequently, many studies on BCG efficacy have been carried out, with highly variable results, ranging from 0 to 90% efficacy. The reasons for this heterogeneity are not well understood. Large clinical studies have shown that booster vaccinations with BCG do not improve the BCG efficacy. Therefore, new vaccines are urgently needed. Today, there are essentially two lines of efforts being pursued in several laboratories. One of them aims at replacing BCG with superior vaccines. This strategy focuses either on improving existing BCG by constructing strains that overproduce certain protective antigens and/or by improving its immunogenicity, or on starting anew by genetically attenuating virulent Mycobacterium tuberculosis. The second line of research aims at adding onto BCG vaccination, such as a heterologous prime-boost strategy. For this strategy BCG is used as a first vaccine, followed by individual antigens as a booster. These antigens can be presented in several different ways, and preference is currently given to the so-called latency antigens. Both approaches have yielded encouraging results in animal models, and some of them have now entered clinical trials. Although still far from human applications, it is hoped that these strategies will ultimately help to reduce the enormous burden that is caused by tuberculosis.
如今,仅有一类疫苗可用于预防结核病。这种疫苗名为卡介苗(BCG),约在100年前研发出来,至今已接种至少30亿次。最初的多中心研究表明,其对儿童结核死亡率的预防效果高达93%。随后,针对卡介苗效果开展了许多研究,结果差异极大,预防效果从0%到90%不等。造成这种异质性的原因尚不清楚。大型临床研究表明,卡介苗加强接种并不能提高其预防效果。因此,迫切需要新型疫苗。如今,多个实验室主要在两条路线上开展研究。其中一条旨在用更优的疫苗取代卡介苗。该策略要么通过构建能过量产生某些保护性抗原的菌株和/或提高其免疫原性来改进现有的卡介苗,要么通过对强毒结核分枝杆菌进行基因减毒来重新研发。第二条研究路线旨在在卡介苗接种基础上进行补充,比如采用异源初免 - 加强策略。对于该策略,卡介苗用作首种疫苗,随后接种单个抗原作为加强剂。这些抗原可以通过几种不同方式呈现,目前更倾向于所谓的潜伏抗原。这两种方法在动物模型中均取得了令人鼓舞的结果,其中一些现已进入临床试验阶段。尽管距离应用于人类仍很遥远,但希望这些策略最终能有助于减轻结核病造成的巨大负担。