Novel nanoscale bacteriophage-based single-domain antibodies for the therapy of systemic infection caused by Candida albicans

Sci Rep. 2016 Aug 25:6:32256. doi: 10.1038/srep32256.

Abstract

Candida albicans (C. albicans) is an important human commensal and opportunistic fungal pathogen. Secreted aspartyl proteinases (Saps) are a major virulence trait of C. albicans, and among these proteases Sap2 has the highest expression levels. It is possible that antibodies against Sap2 could provide an antifungal effect. In this study, two phages displaying anti-rSap2 single chain variable fragments (scFvs) were screened from human single fold scFv libraries, and their potential therapeutic roles were evaluated using a murine model infected by C. albicans. The in vivo efficacies were assessed by mortality rates, fungal burden and histological examination. Overall survival rates were significantly increased while the colony counts and infectious foci were significantly decreased after treatment with the scFv-phages relative to the control groups. In order to investigate the immune response provoked by scFv-phages, three kinds of cytokines (Th1, Th2 and Th17 types) were measured and a clear immune response was observed. These findings suggest that anti-rSap2 scFv-phages have potential in the therapy of systemic infection caused by C. albicans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Fungal / chemistry
  • Antibodies, Fungal / genetics
  • Antibodies, Fungal / immunology
  • Antibodies, Fungal / pharmacology*
  • Aspartic Acid Endopeptidases / antagonists & inhibitors*
  • Aspartic Acid Endopeptidases / immunology
  • Bacteriophage M13
  • Candida albicans / immunology*
  • Candidiasis / drug therapy*
  • Candidiasis / genetics
  • Candidiasis / immunology
  • Candidiasis / pathology
  • Disease Models, Animal
  • Female
  • Fungal Proteins / antagonists & inhibitors*
  • Fungal Proteins / immunology
  • Humans
  • Mice, Inbred BALB C
  • Single-Domain Antibodies / chemistry
  • Single-Domain Antibodies / genetics
  • Single-Domain Antibodies / immunology
  • Single-Domain Antibodies / pharmacology*
  • omega-Chloroacetophenone

Substances

  • Antibodies, Fungal
  • Fungal Proteins
  • Single-Domain Antibodies
  • omega-Chloroacetophenone
  • Aspartic Acid Endopeptidases
  • SAP2 protein, Candida