Tangie Emily, Walters Avril, Hsu Nai-Jen, Fisher Michelle, Magez Stefan, Jacobs Muazzam, Keeton Roanne
Division of Immunology, Department of Pathology, Institute of Infectious Disease and Molecular Medicine, Health Sciences Faculty, University of Cape Town, Observatory, South Africa.
South African Tuberculosis Vaccine Initiative, University of Cape Town, Observatory, South Africa.
Immunology. 2022 Feb;165(2):219-233. doi: 10.1111/imm.13431. Epub 2021 Dec 6.
Tuberculosis (TB) and malaria remain serious threats to global health. Bacillus Calmette-Guerin (BCG), the only licensed vaccine against TB protects against severe disseminated forms of TB in infants but shows poor efficacy against pulmonary TB in adults. Co-infections have been reported as one of the factors implicated in vaccine inefficacy. Given the geographical overlap of malaria and TB in areas where BCG vaccination is routinely administered, we hypothesized that virulence-dependent co-infection with Plasmodium species could alter the BCG-specific immune responses thus resulting in failure to protect against Mycobacterium tuberculosis. We compared virulent Plasmodium berghei and non-virulent Plasmodium chabaudi, their effects on B cells, effector and memory T cells, and the outcome on BCG-induced efficacy against M. tuberculosis infection. We demonstrate that malaria co-infection modulates both B- and T-cell immune responses but does not significantly alter the ability of the BCG vaccine to inhibit the growth of M. tuberculosis irrespective of parasite virulence. This malaria-driven immune regulation may have serious consequences in the early clinical trials of novel vaccines, which rely on vaccine-specific T-cell responses to screen novel vaccines for progression to the more costly vaccine efficacy trials.
结核病（TB）和疟疾仍然是对全球健康的严重威胁。卡介苗（BCG）是唯一获得许可的抗结核疫苗，可预防婴儿严重播散型结核病，但对成人肺结核的疗效不佳。据报道，合并感染是疫苗无效的因素之一。鉴于在常规接种卡介苗的地区，疟疾和结核病在地理上存在重叠，我们推测，疟原虫属的毒力依赖性合并感染可能会改变卡介苗特异性免疫反应，从而导致无法预防结核分枝杆菌感染。我们比较了毒力强的伯氏疟原虫和无毒力的查巴迪疟原虫，它们对B细胞、效应T细胞和记忆T细胞的影响，以及对卡介苗诱导的抗结核分枝杆菌感染效力的影响。我们证明，无论寄生虫毒力如何，疟疾合并感染都会调节B细胞和T细胞免疫反应，但不会显著改变卡介苗抑制结核分枝杆菌生长的能力。这种由疟疾驱动的免疫调节可能会对新型疫苗的早期临床试验产生严重影响，这些试验依靠疫苗特异性T细胞反应来筛选新型疫苗，以便推进到成本更高的疫苗效力试验。
