The Jenner Institute, University of Oxford, Oxford, United Kingdom.
Front Immunol. 2023 Oct 5;14:1263457. doi: 10.3389/fimmu.2023.1263457. eCollection 2023.
The development of tuberculosis (TB) vaccines has been hindered by the complex nature of () and the absence of clearly defined immune markers of protection. While Bacillus Calmette-Guerin (BCG) is currently the only licensed TB vaccine, its effectiveness diminishes in adulthood. In our previous research, we identified that boosting BCG with an intranasally administered chimpanzee adenovirus expressing the PPE15 antigen of (ChAdOx1.PPE15) improved its protection. To enhance the vaccine's efficacy, we combined PPE15 with the other three members of the Esx-5a secretion system and Ag85A into a multi-antigen construct (5Ag). Leveraging the mucosal administration safety of ChAdOx1, we targeted the site of infection to induce localized mucosal responses, while employing modified vaccinia virus (MVA) to boost systemic immune responses. The combination of these antigens resulted in enhanced BCG protection in both the lungs and spleens of vaccinated mice. These findings provide support for advancing ChAdOx1.5Ag and MVA.5Ag to the next stages of vaccine development.
结核分枝杆菌（TB）疫苗的开发受到其复杂性质的阻碍，并且缺乏明确的保护性免疫标志物。卡介苗（BCG）目前是唯一获得许可的结核分枝杆菌疫苗，但它在成年期的效果会减弱。在我们之前的研究中，我们发现用鼻内给予表达结核分枝杆菌 PPE15 抗原的黑猩猩腺病毒（ChAdOx1.PPE15）来增强 BCG 的效果。为了提高疫苗的疗效，我们将 PPE15 与 Esx-5a 分泌系统的另外三个成员和 Ag85A 一起纳入一个多抗原构建体（5Ag）。利用 ChAdOx1 的黏膜给药安全性，我们将感染部位作为目标，以诱导局部黏膜反应，同时使用改良痘苗病毒（MVA）来增强全身免疫反应。这些抗原的组合导致接种疫苗的小鼠肺部和脾脏中的 BCG 保护作用增强。这些发现为推进 ChAdOx1.5Ag 和 MVA.5Ag 进入疫苗开发的下一阶段提供了支持。
