Department of Veterinary Microbiology and Preventive Medicine, Iowa State University, Ames, IA, USA.
Sci Rep. 2019 Nov 5;9(1):15996. doi: 10.1038/s41598-019-52565-z.
The Mycobacterium bovis Bacillus Calmette-Guerin (BCG) vaccine is administered parenterally to infants and young children to prevent tuberculosis (TB) infection. However, the protection induced by BCG is highly variable and the vaccine does not prevent pulmonary TB, the most common form of the illness. Until improved TB vaccines are available, it is crucial to use BCG in a manner which ensures optimal vaccine performance. Immunization directly to the respiratory mucosa has been shown to promote greater protection from TB in animal models. γδ T cells play a major role in host defense at mucosal sites and are known to respond robustly to mycobacterial infection. Their positioning in the respiratory mucosa ensures their engagement in the response to aerosolized TB vaccination. However, our understanding of the effect of respiratory BCG vaccination on γδ T cell responses in the lung is unknown. In this study, we used a calf model to investigate the immunogenicity of aerosol BCG vaccination, and the phenotypic profile of peripheral and mucosal γδ T cells responding to vaccination. We observed robust local and systemic M. bovis-specific IFN-γ and IL-17 production by both γδ and CD4 T cells. Importantly, BCG vaccination induced effector and memory cell differentiation of γδ T cells in both the lower airways and peripheral blood, with accumulation of a large proportion of effector memory γδ T cells in both compartments. Our results demonstrate the potential of the neonatal calf model to evaluate TB vaccine candidates that are to be administered via the respiratory tract, and suggest that aerosol immunization is a promising strategy for engaging γδ T cells in vaccine-induced immunity against TB.
牛型分枝杆菌卡介苗(BCG)疫苗通过注射方式接种给婴幼儿,以预防结核病(TB)感染。然而,BCG 诱导的保护作用具有高度可变性,并且该疫苗并不能预防最常见的疾病形式——肺结核。在更好的 TB 疫苗问世之前,以确保疫苗最佳性能的方式使用 BCG 至关重要。研究表明,直接对呼吸道黏膜进行免疫接种可促进动物模型中对 TB 的更大保护作用。γδ T 细胞在黏膜部位的宿主防御中起主要作用,已知其对分枝杆菌感染有强烈反应。它们在呼吸道黏膜中的定位确保了它们对雾化 TB 疫苗接种的反应。然而,我们对呼吸道 BCG 接种对肺部 γδ T 细胞反应的影响知之甚少。在这项研究中,我们使用小牛模型来研究雾化 BCG 接种的免疫原性,以及对疫苗接种产生反应的外周和黏膜 γδ T 细胞的表型特征。我们观察到γδ 和 CD4 T 细胞均产生了强烈的局部和全身牛分枝杆菌特异性 IFN-γ 和 IL-17 产生。重要的是,BCG 接种诱导了呼吸道和外周血中 γδ T 细胞的效应器和记忆细胞分化,并且在两个部位都积累了大量的效应记忆 γδ T 细胞。我们的研究结果表明,新生小牛模型具有评估通过呼吸道给药的 TB 疫苗候选物的潜力,并表明雾化免疫接种是一种有前途的策略,可以使 γδ T 细胞参与疫苗诱导的针对 TB 的免疫反应。