Abera Bioscience AB, Uppsala, Sweden; Group of Molecular Microbiology, Amsterdam Institute for Life and Environment (A-LIFE), Vrije Universiteit, Amsterdam, the Netherlands.
Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
Biomed Pharmacother. 2024 Nov;180:117563. doi: 10.1016/j.biopha.2024.117563. Epub 2024 Oct 13.
Chlamydia trachomatis causes the most prevalent bacterial sexually transmitted infection worldwide. Its complex lifecycle and the lack of appropriate antigen delivery vehicles make it difficult to develop an effective C. trachomatis vaccine. Recently, bacterial protein bodies (PBs) have emerged as promising bioparticles for vaccine antigen delivery. By developing a PB-tag for translational fusion, we were able to induce the aggregation of recombinant antigens expressed in Escherichia coli into PBs. Here, we investigated the immunogenicity and efficacy of PBs containing either the C. trachomatis MOMP-derived CTH522-SP or HtrA antigen in mice. Intradermal administration of c-di-AMP-adjuvanted PB-CTH522-SP and PB-HtrA vaccines, produced in an LPS-detoxified E. coli strain, induced antigen-specific cellular immunity, as measured by significant release of IFN-γ and IL17a in draining cervical lymph node and splenic cell cultures. Moreover, significant induction of HtrA-specific IFN-γ expressing CD4 and CD8 T cells was detected in the spleens. While immunization with the two PB vaccines led to prominent levels of specific antibodies in both serum and vaginal compartments, only antiserum against PB-CTH522-SP exhibited C. trachomatis-specific neutralization activity. Importantly, intradermal immunization with PB-CTH522-SP significantly reduced bacterial counts following C. trachomatis genital challenge. These data highlight the potential of the PB-based platform for the development of C. trachomatis vaccines.
沙眼衣原体是全球最常见的细菌性性传播感染病原体。其复杂的生命周期和缺乏适当的抗原递呈载体使得开发有效的沙眼衣原体疫苗变得困难。最近，细菌蛋白体（PBs）已成为有前途的疫苗抗原递呈生物颗粒。通过开发翻译融合的 PB 标签，我们能够诱导在大肠杆菌中表达的重组抗原聚集到 PBs 中。在这里，我们研究了含有沙眼衣原体 MOMP 衍生的 CTH522-SP 或 HtrA 抗原的 PBs 在小鼠中的免疫原性和功效。用 c-di-AMP 佐剂的 PB-CTH522-SP 和 PB-HtrA 疫苗经皮内给药，在 LPS 解毒的大肠杆菌菌株中产生，诱导抗原特异性细胞免疫，如在引流颈淋巴结和脾细胞培养物中 IFN-γ 和 IL17a 的显著释放所测量的。此外，在脾脏中检测到 HtrA 特异性 IFN-γ 表达的 CD4 和 CD8 T 细胞的显著诱导。虽然两种 PB 疫苗的免疫接种导致血清和阴道部位均产生显著水平的特异性抗体，但只有针对 PB-CTH522-SP 的抗血清显示出针对沙眼衣原体的中和活性。重要的是，经皮内免疫接种 PB-CTH522-SP 可显著减少沙眼衣原体生殖道感染后的细菌计数。这些数据突出了基于 PB 的平台在开发沙眼衣原体疫苗方面的潜力。
