Schepers K, Dirix V, Mouchet F, Verscheure V, Lecher S, Locht C, Mascart F
Laboratory of Vaccinology and Mucosal Immunity, Université Libre de Bruxelles (U.L.B.), Brussels, Belgium; Immunodeficiency Unit, Hôpital Erasme, Université libre de Bruxelles (U.L.B.), Brussels, Belgium.
Laboratory of Vaccinology and Mucosal Immunity, Université Libre de Bruxelles (U.L.B.), Brussels, Belgium.
Vaccine. 2015 Feb 18;33(8):1077-83. doi: 10.1016/j.vaccine.2014.12.011. Epub 2015 Jan 9.
The search for novel vaccines against tuberculosis (TB) would benefit from in-depths knowledge of the human immune responses to Mycobacterium tuberculosis (Mtb) infection. Here, we characterised in a low TB incidence country, the immune responses to a new candidate vaccine antigen against TB, the heparin-binding haemagglutinin (HBHA), in young children in contact with an active TB case (aTB). Children with no history of BCG vaccination were compared to those vaccinated at birth to compare the initial immune responses to HBHA with secondary immune responses. Fifty-eight children with aTB and 76 with latent TB infection (LTBI) were included and they were compared to 90 non-infected children. Whereas Mtb-infected children globally secreted more interferon-gamma (IFN-γ) in response to HBHA compared to the non-infected children, these IFN-γ concentrations were higher in previously BCG-vaccinated compared to non-vaccinated children. The IFN-γ concentrations were similar in LTBI and aTB children, but appeared to differ qualitatively. Whereas the IFN-γ secretion induced by native methylated and recombinant non-methylated HBHA were well correlated for aTB, this was not the case for LTBI children. Thus, Mtb-infected young children develop IFN-γ responses to HBHA that are enhanced by prior BCG vaccination, indicating BCG-induced priming, thereby supporting a prime-boost strategy for HBHA-based vaccines. The qualitative differences between aTB and LTBI in their HBHA-induced IFN-γ responses may perhaps be exploited for diagnostic purposes.
寻找新型抗结核疫苗需要深入了解人类对结核分枝杆菌（Mtb）感染的免疫反应。在此，我们在一个结核病发病率较低的国家，对接触活动性结核病病例（aTB）的幼儿针对一种新型结核候选疫苗抗原——肝素结合血凝素（HBHA）的免疫反应进行了特征分析。将未接种卡介苗的儿童与出生时接种过卡介苗的儿童进行比较，以比较对HBHA的初始免疫反应和二次免疫反应。纳入了58例aTB儿童和76例潜伏性结核感染（LTBI）儿童，并将他们与90例未感染儿童进行比较。与未感染儿童相比，Mtb感染儿童总体上对HBHA分泌更多的干扰素-γ（IFN-γ），但与未接种疫苗的儿童相比，先前接种过卡介苗的儿童这些IFN-γ浓度更高。LTBI儿童和aTB儿童的IFN-γ浓度相似，但在性质上似乎有所不同。对于aTB儿童，天然甲基化和重组非甲基化HBHA诱导的IFN-γ分泌具有良好的相关性，但LTBI儿童并非如此。因此，Mtb感染的幼儿对HBHA产生IFN-γ反应，且先前的卡介苗接种可增强这种反应，表明卡介苗诱导了免疫启动，从而支持基于HBHA的疫苗的初免-加强策略。aTB和LTBI在HBHA诱导的IFN-γ反应中的定性差异或许可用于诊断目的。
