Humoral correlates of protection against <em>Mycobacterium tuberculosis</em> following intravenous BCG vaccination in rhesus macaques

Altering Bacille Calmette-Guérin (BCG) immunization from low-dose intradermal (i.d.) to high-dose intravenous (i.v.) vaccination provides a high level of protection against (). In addition to strong T cell immunity, i.v. BCG drives robust humoral immune responses that track with bacterial control. However, given the near-complete protection afforded by high-dose i.v. BCG immunization, a precise correlate of protection was difficult to define. Here we leveraged plasma and bronchoalveolar lavage fluid (BAL) from a cohort of rhesus macaques that received decreasing doses of i.v. BCG and aimed to define correlates of immunity following challenge. We show an i.v. BCG dose-dependent induction of mycobacterial-specific humoral immune responses. Antibody responses at peak immunogenicity predicted bacterial control post-challenge. Multivariate analyses revealed antibody-mediated complement and natural killer (NK) cell-activating humoral networks as key signatures of protective immunity. This work extends our understanding of humoral biomarkers and potential mechanisms of i.v. BCG-mediated protection against .Health sciences; Immunology; Pathophysiology

将卡介苗（BCG）免疫从低剂量皮内（i.d.）接种改为高剂量静脉（i.v.）接种可对（某种疾病，原文此处缺失相关内容）提供高水平的保护。除了强大的T细胞免疫外，静脉接种卡介苗还能激发强烈的体液免疫反应，从而控制细菌。然而，鉴于高剂量静脉接种卡介苗提供了近乎完全的保护，很难确定一种精确的保护相关性。在此，我们利用了一组接受不同剂量静脉接种卡介苗的恒河猴的血浆和支气管肺泡灌洗液（BAL），旨在确定（某种疾病，原文此处缺失相关内容）感染后的免疫相关性。我们发现静脉接种卡介苗可诱导结核分枝杆菌特异性体液免疫反应，且呈剂量依赖性。免疫原性达到峰值时的抗体反应可预测感染后的细菌控制情况。多变量分析显示，抗体介导的补体和自然杀伤（NK）细胞激活的体液网络是保护性免疫的关键特征。这项工作加深了我们对体液生物标志物以及静脉接种卡介苗介导的针对（某种疾病，原文此处缺失相关内容）的保护潜在机制的理解。健康科学；免疫学；病理生理学