South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease & Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.
Fred Hutchinson Cancer Research Center (FHCRC), Seattle, WA, USA.
Commun Biol. 2020 Oct 9;3(1):563. doi: 10.1038/s42003-020-01288-3.
We characterize the breadth, function and phenotype of innate and adaptive cellular responses in a prevention of Mycobacterium tuberculosis infection trial. Responses are measured by whole blood intracellular cytokine staining at baseline and 70 days after vaccination with H4:IC31 (subunit vaccine containing Ag85B and TB10.4), Bacille Calmette-Guerin (BCG, a live attenuated vaccine) or placebo (n = ~30 per group). H4:IC31 vaccination induces Ag85B and TB10.4-specific CD4 T cells, and an unexpected NKT subset, that expresses IFN-γ, TNF and/or IL-2. BCG revaccination increases frequencies of CD4 T cell subsets that either express Th1 cytokines or IL-22, and modestly increases IFNγ-producing NK cells. In vitro BCG re-stimulation also triggers responses by donor-unrestricted T cells, which may contribute to host responses against mycobacteria. BCG, which demonstrated efficacy against sustained Mycobacterium tuberculosis infection, modulates multiple immune cell subsets, in particular conventional Th1 and Th22 cells, which should be investigated in discovery studies of correlates of protection.
我们描述了在预防结核分枝杆菌感染试验中固有和适应性细胞反应的广度、功能和表型。通过在接种 H4：IC31（含有 Ag85B 和 TB10.4 的亚单位疫苗）、卡介苗（一种减毒活疫苗）或安慰剂后 70 天对全血进行细胞内细胞因子染色来测量反应（每组约 30 人）。H4：IC31 疫苗接种诱导 Ag85B 和 TB10.4 特异性 CD4 T 细胞，以及意想不到的 NKT 亚群，其表达 IFN-γ、TNF 和/或 IL-2。BCG 再接种增加了表达 Th1 细胞因子或 IL-22 的 CD4 T 细胞亚群的频率，并适度增加了 IFNγ 产生的 NK 细胞。体外 BCG 再刺激也触发了供体不受限制的 T 细胞的反应，这可能有助于宿主对分枝杆菌的反应。BCG 对持续的结核分枝杆菌感染显示出疗效，调节多种免疫细胞亚群，特别是传统的 Th1 和 Th22 细胞，这应该在保护相关性的发现研究中进行研究。
