Department of Tropical Diseases, Naval Medical University, Shanghai 200433, China.
Viruses. 2023 Oct 19;15(10):2123. doi: 10.3390/v15102123.
Bacillus Calmette-Guerin (BCG), the only current vaccine against tuberculosis (TB) that is licensed in clinics, successfully protects infants and young children against several TB types, such as TB meningitis and miliary TB, but it is ineffective in protecting adolescents and adults against pulmonary TB. Thus, it is a matter of the utmost urgency to develop an improved and efficient TB vaccine. In this milieu, virus-like particles (VLPs) exhibit excellent characteristics in the field of vaccine development due to their numerous characteristics, including but not limited to their good safety without the risk of infection, their ability to mimic the size and structure of original viruses, and their ability to display foreign antigens on their surface to enhance the immune response. In this study, the HPV16 L1 capsid protein (HPV16L1) acted as a structural vaccine scaffold, and the extracellular domain of Ag85B was selected as the immunogen and inserted into the FG loop of the HPV16 L1 protein to construct chimeric HPV16L1/Ag85B VLPs. The chimeric HPV16L1/Ag85B VLPs were produced via the expression system and purified via discontinuous Optiprep density gradient centrifugation. The humoral and T cell-mediated immune response induced by the chimeric HPV16L1/Ag85B VLP was studied in female C57BL/c mice. We demonstrated that the insertion of the extracellular domain of Ag85B into the FG loop of HPV16L1 did not affect the in vitro stability and self-assembly of the chimeric HPV16L1/Ag85B VLPs. Importantly, it did not interfere with the immunogenicity of Ag85B. We observed that the chimeric HPV16L1/Ag85B VLPs induced higher Ag85B-specific antibody responses and elicited significant Ag85B-specific T cell immune responses in female C57BL/c mice compared with recombinant Ag85B. Our findings provide new insights into the development of novel chimeric HPV16L1/TB VLP-based vaccine platforms for controlling TB infection, which are urgently required in low-income and developing countries.
卡介苗（BCG）是目前唯一获准在临床使用的结核病（TB）疫苗，可成功保护婴儿和幼儿免受几种结核病类型的侵害，如结核性脑膜炎和粟粒性结核病，但对青少年和成年人预防肺结核无效。因此，开发一种改良的、有效的结核病疫苗是当务之急。在这种情况下，病毒样颗粒（VLPs）由于其众多特性，在疫苗开发领域表现出极好的特性，包括但不限于它们具有良好的安全性，没有感染风险，能够模拟原始病毒的大小和结构，并且能够在其表面展示外来抗原以增强免疫反应。在这项研究中，HPV16 L1 衣壳蛋白（HPV16L1）作为结构疫苗支架，选择 Ag85B 的细胞外结构域作为免疫原并插入 HPV16 L1 蛋白的 FG 环中，构建嵌合 HPV16L1/Ag85B VLPs。嵌合 HPV16L1/Ag85B VLPs 通过表达系统产生，并通过不连续 Optiprep 密度梯度离心进行纯化。在雌性 C57BL/c 小鼠中研究了嵌合 HPV16L1/Ag85B VLP 诱导的体液和 T 细胞介导的免疫反应。我们证明，Ag85B 的细胞外结构域插入 HPV16L1 的 FG 环不会影响嵌合 HPV16L1/Ag85B VLPs 的体外稳定性和自组装。重要的是，它不会干扰 Ag85B 的免疫原性。我们观察到，与重组 Ag85B 相比，嵌合 HPV16L1/Ag85B VLPs 在雌性 C57BL/c 小鼠中诱导更高的 Ag85B 特异性抗体反应，并引发显著的 Ag85B 特异性 T 细胞免疫反应。我们的研究结果为开发新型嵌合 HPV16L1/TB VLP 为基础的疫苗平台提供了新的见解，这是低收入和发展中国家迫切需要的。
