Faculty of Infectious and Tropical Diseases, Department of Immunology and Infection, London School of Hygiene & Tropical Medicine, London, UK.
Eur J Immunol. 2012 Sep;42(9):2511-22. doi: 10.1002/eji.201142297. Epub 2012 Aug 1.
Heparin-binding haemagglutinin (HBHA)-specific immune responses have been linked to protection against tuberculosis (TB). We investigated the hypothesis that BCG vaccination of human infants primes an HBHA-specific response, using multiplex to measure secreted cytokines and chemokines following HBHA and Mycobacterium tuberculosis purified protein derivative (PPD) stimulation of diluted whole blood samples from BCG-vaccinated or -unvaccinated infants. Of 42 analytes measured, 24 and 32 significant, BCG-associated increases were detected in response to HBHA and PPD, respectively. Both response profiles included Th-1, Th-2, Th-17 and inflammatory cytokines and chemokines (e.g. IFN-γ, TNF-α, IL-5, IL-10, IL-13, IL-17, MIP-1α and MIP-1β). We also found that six of the seven responses most closely correlated with IFN-γ were common to both HBHA and PPD. Notably, all HBHA-specific secretion of cytokines and chemokines from infant samples was dependent on previous BCG vaccination. Also, long-term persistence of HBHA-specific responses was found in adolescents with evidence of infant BCG vaccination. This study demonstrates for the first time BCG priming of an HBHA-specific immune response in infants that is characterised by a broad cytokine and chemokine signature. It also suggests a number of BCG vaccination associated, HBHA-induced responses that should be useful for future studies of biomarkers of protection against TB.
肝素结合血凝素 (HBHA) 特异性免疫反应与结核病 (TB) 的保护有关。我们通过使用多重分析方法测量经 HBHA 和结核分枝杆菌纯蛋白衍生物 (PPD) 刺激稀释的全血样本后分泌的细胞因子和趋化因子,来研究卡介苗 (BCG) 疫苗接种是否会引发 HBHA 特异性反应的假设。在测量的 42 种分析物中,有 24 种和 32 种在 HBHA 和 PPD 刺激下与 BCG 相关的显著增加。两种反应谱均包括 Th1、Th2、Th17 和炎症细胞因子和趋化因子(例如 IFN-γ、TNF-α、IL-5、IL-10、IL-13、IL-17、MIP-1α 和 MIP-1β)。我们还发现,与 IFN-γ 最密切相关的七种反应中的六种与 HBHA 和 PPD 都密切相关。值得注意的是,婴儿样本中所有 HBHA 特异性细胞因子和趋化因子的分泌都依赖于先前的 BCG 接种。此外,在有婴儿 BCG 接种证据的青少年中,也发现了 HBHA 特异性反应的长期持续存在。这项研究首次证明了 BCG 疫苗接种在婴儿中引发 HBHA 特异性免疫反应,其特征是广泛的细胞因子和趋化因子特征。它还提示了一些与 BCG 接种相关的、由 HBHA 诱导的反应,这些反应可能对未来研究结核病保护的生物标志物有用。