Vilaplana C, Ruiz-Manzano J, Gil O, Cuchillo F, Montané E, Singh M, Spallek R, Ausina V, Cardona P J
Unitat de Tuberculosi Experimental, Fundacio Institut per a la Investigació en Ciències de la Salut Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Catalonia, Spain.
Scand J Immunol. 2008 Jun;67(6):610-7. doi: 10.1111/j.1365-3083.2008.02103.x. Epub 2008 Apr 4.
RUTI is a vaccine consisting of Mycobacterium tuberculosis bacilli grown in stress conditions that is fragmented, detoxified and liposomed. RUTI was designed to shorten the treatment of latent tuberculosis infection (LTBI) with isoniazid from 9 months to just 1 month, by additional treatment with two inoculations of RUTI 4 weeks apart. During the validation process for monitoring the immunogenicity of administration of RUTI in a Phase I clinical trial, the question arose whether to introduce the tuberculin skin test (TST) in the screening of non-LTBI volunteers. This study was designed to evaluate the effect of TST on subsequent different T-cell interferon-gamma release assay (TIGRA) responses, using a spectrum of M. tuberculosis-related antigens (ESAT-6, CFP-10, 16 kDa, 19 kDa, MPT64, Ag 85B, 38 kDa, hsp65, PPD and BCG). The results showed an increase in post-TST response even in non-LTBI subjects for most antigens tested, as measured both by whole blood assay (WBA) and ELISPOT. Increased ELISPOT response decreased toward pre-TST levels within 1 month whereas the WBA response did not. Taking into account that there is no definitive correlation between TST and TIGRA tests to diagnose LTBI and the feasibility that TST might alter the immune monitoring included in clinical trials, these data suggest that TST determination should be carefully planned to avoid any interference with TIGRA.
RUTI是一种疫苗,由在应激条件下生长的结核分枝杆菌制成,经过破碎、解毒和脂质体化处理。RUTI旨在通过每隔4周接种两次RUTI进行额外治疗,将异烟肼治疗潜伏性结核感染(LTBI)的时间从9个月缩短至仅1个月。在一项I期临床试验中监测RUTI给药免疫原性的验证过程中,出现了是否在非LTBI志愿者筛查中引入结核菌素皮肤试验(TST)的问题。本研究旨在使用一系列结核分枝杆菌相关抗原(ESAT-6、CFP-10、16 kDa、19 kDa、MPT64、Ag 85B、38 kDa、hsp65、PPD和卡介苗)评估TST对随后不同T细胞干扰素-γ释放试验(TIGRA)反应的影响。结果显示,即使在非LTBI受试者中,对于大多数测试抗原,通过全血检测(WBA)和ELISPOT测量,TST后反应均有所增加。ELISPOT反应增加在1个月内降至TST前水平,而WBA反应则没有。考虑到TST与TIGRA检测在诊断LTBI方面没有明确的相关性,以及TST可能改变临床试验中免疫监测的可行性,这些数据表明,应谨慎规划TST检测,以避免对TIGRA产生任何干扰。