中国结核病疫苗研发现状及展望

卡介苗是目前唯一在市场上使用的结核病疫苗，主要可以减少儿童结核性脑膜炎和播散性结核病的发生，但是对青少年和成年人的保护效果有限。为实现“终结结核病流行目标”,研发和推广针对全年龄段、有效的新型结核病疫苗至关重要。鼓励研发新型结核病疫苗、参与国际多中心临床试验，有助于激发内部活力、缩短结核病疫苗研发周期、加快疫苗上市和推广速度。作者梳理了中国进入临床研究阶段的结核病疫苗现状、相关支持性政策和国际多中心临床试验的基本要求等，并对未来结核病疫苗的研发进行了展望。     

结核疫苗研究的历史与现状

由于结核病缺乏有效的疫苗保护，发病率持续增高，成为人类传染病中继艾滋病之后的第二大杀手。减毒牛型结核分枝杆菌——卡介苗是目前许多国家批准应用于人体的惟一结核病疫苗。然而，卡介苗对成人肺结核的保护效率很低，研制新型结核病疫苗迫在眉睫。多种类型的新型疫苗，包括重组卡介苗疫苗、营养缺陷型结核分枝杆菌疫苗、蛋白质多肽疫苗、DNA疫苗、以病毒为载体的结核分枝杆菌亚单位疫苗等被广泛研究。至2005年，已有120种以上的疫苗进行了动物实验研究，至少有5个疫苗已进入Ⅰ期临床试验。     

从卡介苗到核酸疫苗谈结核病的预防

目的讨论结核病的最佳预防手段。方法综述传统卡介苗和多种基因工程疫苗对结核病的保护作用和面临的问题。结果卡介苗作为一种传统的预防结核病的疫苗，在学术界其保护作用有争议，研发新的结核病疫苗已经成为趋势。结论基因工程疫苗将是下一个安全、有效、有可能代替卡介苗的结核病疫苗。     

俄抗艾滋病疫苗已进入临床试验

据好医生网10月9日报道，俄罗斯“向量”国家病毒学与生物技术学科研中心研制出一种新型抗艾滋病疫苗，目前正在对该疫苗进行临床试验。 俄罗斯科学院院士、遗传学家弗拉基米尔舒姆内指出，目前世界上还没有抗艾滋病的疫苗。所有最近研制出的三种抗艾滋病疫苗都没有通过临床试验。现在研制出的疫苗将成为有效的治疗性艾滋病疫苗。[第一段]     

结核分枝杆菌实验室获得性感染事件分析

加强疫苗、结核病新药和诊断方法研究是当前“遏制结核病策略”之一。为此,国家在“十一五”科技重大专项中设立了“艾滋病和病毒性肝炎等重大传染病防治”专项,其中包括结核病防治课题。而在展开结核病防治研究的过程中,如何避免实验室获得性感染则是首先需要解决的问题。本研究收集了20世纪50年代以来国际上文献报道的实验室获得性结核感染事件,并对事件原因进行了分析,以期为我国实验室安全开展Mtb研究提供参考。     

美国“最有希望”艾滋病疫苗临床试验失败

据好医生网10月10日报道，艾滋病（AIDS）疫苗研究遭受了灾难性打击，一个最有希望的艾滋病疫苗的临床试验宣布失败。 美国国家过敏和传染性疾病研究所艾滋病疫苗项目负责人佩吉约翰斯顿指出，美国国家过敏和传染性疾病研究所和一个名为HIV疫苗联盟的学术机构组成团队，开始实施这项名为“步伐”（Step）的V520全球性人体试验。[第一段]     

预防结核病接种卡介苗的临床试验中功效差异的再调查

背景:复阅了主要的卡介苗接种预防结核病对照试验的结果。目的:研究在不同试验中疫苗功效悬殊差异的可能原因,特别在印度南方的Chingleput试验中开始几年的明显相反作用。观察:(1)如果疫苗功效的评定中有一个对疫苗接种发生相反作用的亚群,则可造成全面功效的降低甚至逆转。(2)数次试验在评定中包括许多对结核菌素原始敏感性低的人,其原因为环境中非结核分支杆菌感染,或结核分支杆菌感染。据认为,在前一亚群中,疫苗的功效可能有中度降低,并认定后一亚群在疫苗接种后不久,可能有结核病再度活动的危险,其原因可能为其弱的敏感性得到加强而发生病灶反应。(3)几次试验中功效的低下,和Chingleput出现的早期相反作用,大体上符合这一假说。结论:结核杆菌感染后结核菌素敏感性弱者卡介苗接种引起的临床结核病,可能是临床试验中出现功效差异的重要原因。     

结核分枝杆菌Ag85A/HSP70 DNA疫苗的真核表达与免疫效应研究

目前卡介苗（BCG）作为临床上惟一使用的预防结核病的疫苗,效果并不稳定.同时BCG的接种会使结核菌素试验阳性,对结核病的诊断产生干扰,延误治疗时间,因此研制新疫苗成为当前结核病防治的首要任务.我们将结核分枝杆菌Ag85A和HSP70编码基因，以PCI-neo为载体，连接构建了PCI-Ag85A/HSP70 DAN疫苗，观察其免疫效应，以期用于结核病的防治工作。     

卫生部开展结核病防治规划实验室专项督导

为了解全国结核病控制规划进展情况，加强结核病实验室质量控制，根据卫生部疾病控制司的要求，中国疾病预防控制中心结核病防治临床中心国家结核病参比实验室组织人员于2005年9月至11月期间对八省进行了结核病防治规划实验室专项督导。     

新型结核疫苗的研究进展

结核病(TB)仍然是世界上最致命的传染病之一,其发病率持续增高。如何对结核病进行有效的预防成了现在面临的主要问题。而目前广泛使用的卡介苗(BCG)疫苗仅对结核病提供有限的保护,特别是对成人型结核病起作用与否存有较大争议,因此新型的结核疫苗便成为抗结核的有利举措。本文把15个处于临床实验阶段的新型候选疫苗,按照免疫策略将其分为代替卡介苗的初选疫苗,BCG初免后的增强疫苗和预防感染者发病的治疗性疫苗加以综述,以期为防治结核病提供参考。     

结核病无处不在

2007年"3.24世界结核病日"主题为:结核病无处不在。目的是提供一个紧迫感和共同责任的信息,通过各级政府统一行动,争取实现无结核世界目标。2007年结核病无处不在主题强调,虽然结核病是可预防并可治愈的疾病,但它仍然是全球紧急状态。该主题反映了结核     

Adjunct immune therapy of first-diagnosed TB, relapsed TB, treatment-failed TB, multidrug-resistant TB and TB/HIV

Aim: To evaluate the effect of an adjunct immunotherapy in randomized double-blind, placebo-controlled Phase IIb trial involving 123 TB patients. Methods: Patients were randomly allocated into two arms: one (n = 62) received a once-daily pill of V-5 Immunitor? (V5) and the other (control; n= 61) received placebo for 30 days in addition to first- or second-line TB drugs administered under directly observed therapy. The subjects in V5 and placebo arms had first-diagnosed, relapsed, treatment-failed and multidrug-resistant TB at ratios of 17:21:11:13 and 20:19:14:8, respectively; among them, ten and seven had HIV coinfection, respectively. Results: After 1 month, 55 out of 62 patients (88.7%) became sputum smear-negative in the V5 arm (p < 0.0001), whereas in the placebo group, nine out of 61 (14.8%) had converted. The conversion rate among V5 recipients was similar, regardless of whether TB was drug-sensitive, drug-resistant or with HIV. V5 downregulated TB-associated inflammation, as shown by the normalization of elevated leukocyte counts (8.7 vs 6.3 × 10 (9)/l; p < 0.0001) and decreased erythrocyte sedimentation rate (22.8 vs 12.6 mm/h; p < 0.0001), whereas among placebo recipients, changes were smaller (8.9 vs 8.2 × 10 (9)/l and 25.1 vs 19.9 mm/h). Thirty three (54.1%) placebo patients gained on average 0.8 kg (p = 0.0002); by contrast, 57 (91.9%) out of 62 patients in the V5 group gained a mean weight of 2.9 kg (p < 0.0001). No adverse side effects or reactivation of TB were seen at any time. Conclusion: V5 is safe and effective as an immune adjunct to chemotherapy for TB and can potentially reduce the treatment duration down to 1 month.     

Congenital TB associated with asymptomatic maternal endometrial TB

Congenital TB has varied clinical manifestations, and may mimic septicaemia in neonates. Congenital TB is transmitted through the infected placenta via the umbilical vein or inhalation and ingestion of infected amniotic fluid. Endometrial TB usually manifests as infertility; however, congenital TB can be identified in the presence of asymptomatic maternal endometrial TB. We report a case of congenital TB associated with asymptomatic maternal endometrial TB to highlight the need for endometrial biopsy in such cases.     

Parotid TB

TB of the parotid is rare and only about 100 cases have been reported in the world literature. Often the diagnosis is made only after the surgery performed for a suspected neoplasm. We describe three patients with diffuse form of parotidTB without any evidence of tubercular focus elsewhere. Fine needle aspiration cytology confirmed the diagnosis in two cases, while the third case was diagnosed only after surgery.     

Prospects for new TB vaccines: Stop TB Working Group on TB Vaccine Development.

Research towards the development of improved TB vaccines has reached an important turning point. A large number of vaccine candidates such as modified BCG, attenuated Mycobacterium tuberculosis and protein or DNA subunit vaccines, resulting from over a decade of work in experimental laboratory models, are now getting ready for clinical testing. The transition from laboratory to clinical trials has a wide range of strategic and technical implications. Facilities and funding need to be identified for the production of clinical vaccine lots, an issue that is difficult to tackle due to the live organisms in some of the new vaccine candidates; regulatory hurdles need to be overcome; protocols and trial sites need to be developed, for phase III clinical efficacy trials in particular. The Stop TB Working Group on TB Vaccine Development provides a global forum that brings laboratory and clinical researchers together with experts in tuberculosis control and representatives from commercial and non-profit funding agencies to address these issues and to facilitate progress towards the common goal of improved vaccination strategies for tuberculosis.