Immunogenic Potential and Therapeutic Efficacy of Multi‐Epitope Encapsulated Silk Fibroin Nanoparticles against Pseudomonas aeruginosa‐Mediated Urinary Tract Infections

Abstract

AbstractPseudomonas 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.