Coppola Mariateresa, Jurion Fabienne, van den Eeden Susan J F, Tima Hermann Giresse, Franken Kees L M C, Geluk Annemieke, Romano Marta, Ottenhoff Tom H M
Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
In vivo models unit, Immune Response Service, Infectious Diseases in Humans Scientific Directorate, Sciensano, Belgium.
NPJ Vaccines. 2021 Jun 3;6(1):81. doi: 10.1038/s41541-021-00343-2.
Novel tuberculosis (TB)-vaccines preferably should (i) boost host immune responses induced by previous BCG vaccination and (ii) be directed against Mycobacterium tuberculosis (Mtb) proteins expressed throughout the Mtb infection-cycle. Human Mtb antigen-discovery screens identified antigens encoded by Mtb-genes highly expressed during in vivo murine infection (IVE-TB antigens). To translate these findings towards animal models, we determined which IVE-TB-antigens are recognised by T-cells following Mtb challenge or BCG vaccination in three different mouse strains. Eleven Mtb-antigens were recognised across TB-resistant and susceptible mice. Confirming previous human data, several Mtb-antigens induced cytokines other than IFN-γ. Pulmonary cells from susceptible C3HeB/FeJ mice produced less TNF-α, agreeing with the TB-susceptibility phenotype. In addition, responses to several antigens were induced by BCG in C3HeB/FeJ mice, offering potential for boosting. Thus, recognition of promising Mtb-antigens identified in humans validates across multiple mouse TB-infection models with widely differing TB-susceptibilities. This offers translational tools to evaluate IVE-TB-antigens as diagnostic and vaccine antigens.
新型结核病（TB）疫苗最好应具备以下两点：（i）增强先前卡介苗接种所诱导的宿主免疫反应；（ii）针对结核分枝杆菌（Mtb）在整个感染周期中表达的蛋白质。人类Mtb抗原发现筛选确定了由在体内小鼠感染期间高表达的Mtb基因编码的抗原（体内感染结核分枝杆菌抗原）。为了将这些发现转化到动物模型中，我们确定了在三种不同小鼠品系中，结核分枝杆菌攻击或卡介苗接种后哪些体内感染结核分枝杆菌抗原能被T细胞识别。在抗结核和易感小鼠中识别出了11种Mtb抗原。证实了先前的人类数据，几种Mtb抗原除了诱导γ干扰素外还诱导了其他细胞因子。易感的C3HeB/FeJ小鼠的肺细胞产生的肿瘤坏死因子-α较少，这与结核易感性表型一致。此外，卡介苗在C3HeB/FeJ小鼠中诱导了对几种抗原的反应，具有增强的潜力。因此，在人类中鉴定出的有前景的Mtb抗原在多种结核易感性差异很大的小鼠结核感染模型中得到了验证。这为评估体内感染结核分枝杆菌抗原作为诊断和疫苗抗原提供了转化工具。
