已知分枝杆菌对免疫系统产生一系列异源作用。基于分枝杆菌的弗氏完全佐剂是一种有效的非特异性免疫反应刺激剂，用于促进抗体产生的免疫方案中，而牛分枝杆菌卡介苗 (BCG) 疫苗接种除了提供特定保护外，还与降低发病率和死亡率有关在某些人群和年龄组中预防结核病 (TB)。异源抗体在这种现象中的作用（如果有的话）仍不清楚且尚未得到充分研究。我们着手评估感染结核分枝杆菌 (M.tb) 并接种卡介苗或候选结核病疫苗后对一系列不相关病原体的抗体反应疫苗，MTBVAC，在非人类灵长类动物中。我们证明，在低剂量气溶胶感染 MTB 后，针对 SARS-CoV-2、巨细胞病毒、EB 病毒、破伤风类毒素和呼吸道合胞病毒抗原的抗体滴度显着增加.tb。其中一些反应的强度与结核病的严重程度相关。然而，通过皮内、静脉内或气雾剂途径接种 BCG，或皮内递送 MTBVAC，并没有增加针对无关病原体的抗体反应。我们的研究结果表明，异源抗体不太可能导致这些疫苗的非特异性作用。与结核病相关的 B 细胞反应明显失调值得进一步研究，这对 B 细胞癌的风险和新的治疗策略具有潜在影响。版权所有 © 2024 Peralta Alvarez, Jones, Redondo Azema, Davis, White, Sarfas, Dennis, Li,赖特、普恩特斯、基姆达、贝利-拉默斯托弗、阿吉洛、马丁、夏普、麦克肖恩和坦纳。

Mycobacteria are known to exert a range of heterologous effects on the immune system. The mycobacteria-based Freund's Complete Adjuvant is a potent non-specific stimulator of the immune response used in immunization protocols promoting antibody production, and Mycobacterium bovis Bacille Calmette Guérin (BCG) vaccination has been linked with decreased morbidity and mortality beyond the specific protection it provides against tuberculosis (TB) in some populations and age groups. The role of heterologous antibodies in this phenomenon, if any, remains unclear and under-studied.We set out to evaluate antibody responses to a range of unrelated pathogens following infection with Mycobacterium tuberculosis (M.tb) and vaccination with BCG or a candidate TB vaccine, MTBVAC, in non-human primates.We demonstrate a significant increase in the titer of antibodies against SARS-CoV-2, cytomegalovirus, Epstein-Barr virus, tetanus toxoid, and respiratory syncytial virus antigens following low-dose aerosol infection with M.tb. The magnitude of some of these responses correlated with TB disease severity. However, vaccination with BCG administered by the intradermal, intravenous or aerosol routes, or intradermal delivery of MTBVAC, did not increase antibody responses against unrelated pathogens.Our findings suggest that it is unlikely that heterologous antibodies contribute to the non-specific effects of these vaccines. The apparent dysregulation of B cell responses associated with TB disease warrants further investigation, with potential implications for risk of B cell cancers and novel therapeutic strategies.Copyright © 2024 Peralta Alvarez, Jones, Redondo Azema, Davis, White, Sarfas, Dennis, Li, Wright, Puentes, Kimuda, Belij-Rammerstorfer, Aguilo, Martin, Sharpe, McShane and Tanner.