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

Macromol Biosci. 2023 Sep;23(9):e2300074. doi: 10.1002/mabi.202300074. Epub 2023 May 18.

Abstract

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.

Keywords: P. aeruginosa; multi-epitope; silk fibroin nanoparticles; urinary tract infection; vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic
  • Animals
  • Epitopes
  • Fibroins* / pharmacology
  • Mice
  • Mice, Inbred BALB C
  • Nanoparticles* / therapeutic use
  • Pseudomonas aeruginosa
  • Urinary Tract Infections* / drug therapy
  • Urinary Tract Infections* / prevention & control
  • Vaccines*

Substances

  • Fibroins
  • Epitopes
  • aluminum sulfate
  • Vaccines
  • Adjuvants, Immunologic