Development of Drug-Resistant Klebsiella pneumoniae Vaccine via Novel Vesicle Production Technology

ACS Appl Mater Interfaces. 2021 Jul 21;13(28):32703-32715. doi: 10.1021/acsami.1c06701. Epub 2021 Jul 12.

Abstract

Drug resistance of Klebsiella pneumoniae severely threatens human health. Overcoming the mechanisms of K. pneumoniae resistance to develop novel vaccines against drug-resistant K. pneumoniae is highly desired. Here, we report a technology platform that uses high pressure to drive drug-resistant K. pneumoniae to pass through a gap, inducing the formation of stable artificial bacterial biomimetic vesicles (BBVs). These BBVs had little to no bacterial intracellular protein or nucleic acid and had high yields. BBVs were efficiently taken up by dendritic cells to stimulate their maturation. BBVs as K. pneumoniae vaccines had the dual functions of inducing bacteria-specific humoral and cellular immune responses to increase animals' survival rate and reduce pulmonary inflammation and bacterial loads. We believe that BBVs are new-generation technology for bacterial vesicle preparation. Establishment of this BBV vaccine platform can maximally expand preparation technology for vaccines against drug-resistant K. pneumoniae.

Keywords: Klebsiella pneumoniae; biomimetic vesicles; high pressure; homogenization; nanovaccine, drug resistance.

MeSH terms

  • Animals
  • Bacterial Vaccines / chemical synthesis
  • Bacterial Vaccines / immunology
  • Bacterial Vaccines / therapeutic use*
  • Bacterial Vaccines / toxicity
  • Biomimetic Materials / chemical synthesis
  • Biomimetic Materials / therapeutic use*
  • Biomimetic Materials / toxicity
  • Cell Fractionation / methods
  • Drug Resistance, Multiple, Bacterial / drug effects
  • Extracellular Vesicles / immunology*
  • Female
  • Immunity, Cellular / drug effects
  • Immunity, Humoral / drug effects
  • Klebsiella Infections / therapy*
  • Klebsiella pneumoniae / chemistry
  • Klebsiella pneumoniae / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred ICR
  • Pressure

Substances

  • Bacterial Vaccines