a Tuberculosis Research Program Centenary Institute , The University of Sydney , Camperdown , NSW , Australia.
b The University of Sydney , Central Clinical School Faculty of Medicine and Health , Sydney , NSW , Australia.
Expert Rev Vaccines. 2019 Apr;18(4):353-364. doi: 10.1080/14760584.2019.1585246. Epub 2019 Mar 4.
The development of more effective tuberculosis (TB) vaccines is essential for the global control of TB. Recently, there have been major advances in the field, but an important hindrance remains the lack of correlates of protection against TB. This requires each vaccine candidate to undergo clinical efficacy trials based on data from animal protection studies, but the results from animal models do not necessarily predict efficacy in humans.
In this review we summarize our current knowledge of immune mechanisms that may contribute to protective immunity against TB following vaccination and relate these to protective efficacy in animal models and recent clinical trials. Although some initial trials did not reproduce protection against TB in humans, recent trials have demonstrated promising efficacy for three vaccine approaches.
Although CD4 T lymphocytes are essential for protection against TB, there is no clear correlation between conventional CD4 or CD8 T cell responses and protective efficacy of TB vaccines. Recent attention has focused on other immune responses, including donor unrestricted T cells, B lymphocytes, and antibodies. Prospective studies on samples from vaccinated individuals protected in recent trials will allow evaluation of these alternative immune mechanisms as potential correlates of protection.
开发更有效的结核病 (TB) 疫苗对于全球结核病控制至关重要。最近，该领域取得了重大进展，但一个重要的障碍仍然是缺乏针对结核病的保护相关性。这要求每个疫苗候选者都要根据动物保护研究的数据进行临床疗效试验，但是动物模型的结果并不一定能预测对人类的疗效。
在这篇综述中，我们总结了我们目前对免疫机制的了解，这些机制可能有助于接种疫苗后对结核病产生保护性免疫，并将这些机制与动物模型和最近的临床试验中的保护效果联系起来。尽管一些初步试验未能在人体中复制对结核病的保护作用，但最近的试验表明，三种疫苗方法具有有希望的疗效。
虽然 CD4 T 淋巴细胞对于预防结核病至关重要，但 CD4 或 CD8 T 细胞反应的常规指标与结核病疫苗的保护效果之间没有明确的相关性。最近的注意力集中在其他免疫反应上，包括非限定性供体 T 细胞、B 淋巴细胞和抗体。对最近试验中受保护的接种个体样本进行前瞻性研究，将允许评估这些替代免疫机制作为潜在的保护相关性。
