Stewart Erica L, Counoupas Claudio, Quan Diana H, Wang Trixie, Petrovsky Nikolai, Britton Warwick J, Triccas James A
Sydney Infectious Diseases Institute (Sydney ID), Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2006, Australia.
Centre for Infection and Immunity, Centenary Institute, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia.
Vaccines (Basel). 2024 Jan 26;12(2):128. doi: 10.3390/vaccines12020128.
Tuberculosis (TB), caused by , results in approximately 1.6 million deaths annually. BCG is the only TB vaccine currently in use and offers only variable protection; however, the development of more effective vaccines is hindered by a lack of defined correlates of protection (CoP) against . Pulmonary vaccine delivery is a promising strategy since it may promote lung-resident immune memory that can respond rapidly to respiratory infection. In this study, CysVac2, a subunit protein previously shown to be protective against in mouse models, was combined with either Advax adjuvant or a mixture of alum plus MPLA and administered intratracheally into mice. Peripheral immune responses were tracked longitudinally, and lung-local immune responses were measured after challenge. Both readouts were then correlated with protection after infection. Although considered essential for the control of mycobacteria, induction of IFN-γ-expressing CD4 T cells in the blood or lungs did not correlate with protection. Instead, CD4 T cells in the lungs expressing IL-17A correlated with reduced bacterial burden. This study identified pulmonary IL-17A-expressing CD4 T cells as a CoP against and suggests that mucosal immune profiles should be explored for novel CoP.
由[病原体名称未给出]引起的结核病（TB）每年导致约160万人死亡。卡介苗（BCG）是目前唯一正在使用的结核病疫苗，其提供的保护效果参差不齐；然而，由于缺乏针对[病原体名称未给出]的明确保护相关指标（CoP），更有效疫苗的研发受到阻碍。肺部疫苗接种是一种有前景的策略，因为它可能促进肺部驻留免疫记忆，从而能对呼吸道感染迅速做出反应。在本研究中，将先前在小鼠模型中显示对[病原体名称未给出]有保护作用的亚单位蛋白CysVac2与Advax佐剂或明矾加MPLA的混合物相结合，并经气管内注射到小鼠体内。纵向跟踪外周免疫反应，并在攻击后测量肺部局部免疫反应。然后将这两种检测结果与[病原体名称未给出]感染后的保护情况相关联。虽然血液或肺部中表达IFN-γ的CD4 T细胞的诱导被认为对控制分枝杆菌至关重要，但它与保护作用并无关联。相反，肺部中表达IL-17A的CD4 T细胞与细菌载量的降低相关。本研究确定肺部表达IL-17A的CD4 T细胞为针对[病原体名称未给出]的一种保护相关指标，并表明应探索黏膜免疫谱以寻找新的保护相关指标。
