Rezvanirad Azam, Habibi Mehri, Farokhi Mehdi, Asadi Karam Mohammad Reza
Department of Molecular Biology, Pasteur Institute of Iran, Tehran, 1316943551, Iran.
National Cell Bank of Iran, Pasteur Institute of Iran, Tehran, 1316943551, Iran.
Macromol Biosci. 2023 Sep;23(9):e2300074. doi: 10.1002/mabi.202300074. Epub 2023 May 18.
Pseudomonas aeruginosa (P. aeruginosa) causing urinary tract infections (UTIs) are a major concern among hospital-acquired infections. The need for an effective vaccine that reduces the infections is imperative. This study aims to evaluate the efficacy of a multi-epitope vaccine encapsulated in silk fibroin nanoparticles (SFNPs) against P. aeruginosa-mediated UTIs. A multi-epitope is constructed from nine proteins of P. aeruginosa using immunoinformatic analysis, expressed, and purified in BL21 (DE3) cells. The encapsulation efficiency of the multi-epitope in SFNPs is 85% with a mean particle size of 130 nm and 24% of the encapsulated antigen is released after 35 days. The vaccine formulations adjuvanted with SFNPs or alum significantly improve systemic and mucosal humoral responses and the cytokine profile (IFN-γ, IL-4, and IL-17) in mice. Additionally, the longevity of the IgG response is maintained for at least 110 days in a steady state. In a bladder challenge, mice treated with the multi-epitope admixed with alum or encapsulated in SFNPs demonstrate significant protection of the bladder and kidneys against P. aeruginosa. This study highlights the promising therapeutic potential of a multi-epitope vaccine encapsulated in SFNPs or adjuvanted with alum against P. aeruginosa infections.
引起尿路感染（UTIs）的铜绿假单胞菌是医院获得性感染中的一个主要问题。迫切需要一种能减少感染的有效疫苗。本研究旨在评估包裹在丝素蛋白纳米颗粒（SFNPs）中的多表位疫苗对铜绿假单胞菌介导的尿路感染的疗效。利用免疫信息学分析从铜绿假单胞菌的九种蛋白质构建多表位，在BL21（DE3）细胞中表达并纯化。多表位在SFNPs中的包封效率为85%，平均粒径为130nm，35天后24%的包封抗原释放。用SFNPs或明矾佐剂的疫苗制剂显著改善小鼠的全身和黏膜体液反应以及细胞因子谱（IFN-γ、IL-4和IL-17）。此外，IgG反应的持久性在稳定状态下至少维持110天。在膀胱攻毒实验中，用与明矾混合或包裹在SFNPs中的多表位处理的小鼠对膀胱和肾脏表现出显著的保护作用，使其免受铜绿假单胞菌感染。本研究突出了包裹在SFNPs中或用明矾佐剂的多表位疫苗对铜绿假单胞菌感染具有有前景的治疗潜力。
