为下一代结核病疫苗挖掘CD4抗原库，这一成果由哈佛医学院Dan H. Barouch研究组经过不懈努力而取得。2025年9月15日出版的《细胞》杂志发表了这一最新研究成果。

小组对人类CD4 T细胞的靶标抗原在小鼠中进行了功效筛选。该团队发现在保护效果上存在显著的异质性，并且大多数顶级保护性抗原目前尚未进入临床开发阶段。该团队观察到系统发育聚集抗原之间的免疫交叉反应性，反映了共同的CD4表位。研究团队开发了一种由PPE20 （Rv1387）、EsxG （Rv0287）和PE18 （Rv1788）组成的三价mRNA疫苗，在多主题模型中增强并超过了卡介苗的保护作用。最后，研究组观察到84%暴露于结核分枝杆菌的人对这些抗原的细胞免疫反应。这些数据促进了他们对结核病疫苗免疫学的理解，并为临床开发确定了疫苗概念。

据悉，结核病（TB）是世界范围内传染病死亡的主要死因，卡介苗（BCG）仍然是唯一临床批准的疫苗。结核病疫苗开发的一个长期挑战是从大量潜在候选抗原中系统地选择抗原。

附：英文原文

Title: Mining the CD4 antigen repertoire for next-generation tuberculosis vaccines

Author: Samuel J. Vidal, Ninaad Lasrado, Lisa H. Tostanoski, Jayeshbhai Chaudhari, Esther R. Mbiwan, Ganad D. Neka, Ellis A. Strutton, Alejandro A. Espinosa Perez, Daniel Sellers, Julia Barrett, Michelle Lifton, Shoko Wakabayashi, Behnaz Eshaghi, Erica N. Borducchi, Malika Aid, Wenjun Li, Thomas J. Scriba, Ana Jaklenec, Robert Langer, Dan H. Barouch

Issue&Volume: 2025-09-15

Abstract: Tuberculosis (TB) is the leading cause of death from infectious disease worldwide, and Bacillus Calmette-Guérin (BCG) remains the only clinically approved vaccine. An enduring challenge in TB vaccine development is systematic antigen selection from a large repertoire of potential candidates. We performed an efficacy screen in mice of antigens that are targets of CD4 T cells in humans. We found striking heterogeneity in protective efficacy, and most of the top protective antigens are not currently in clinical development. We observed immunologic cross-reactivity among phylogenetically clustered antigens, reflecting common CD4 epitopes. We developed a trivalent mRNA vaccine consisting of PPE20 (Rv1387), EsxG (Rv0287), and PE18 (Rv1788), which augmented and exceeded BCG protection in multiple mouse models. Finally, we observed cellular immune responses to these antigens in 84% of humans exposed to M. tuberculosis. These data advance our understanding of TB vaccine immunology and define a vaccine concept for clinical development.

DOI: 10.1016/j.cell.2025.08.027

Source: https://www.cell.com/cell/abstract/S0092-8674(25)00982-1