Therapy of mucosal candidiasis by expression of an anti-idiotype in human commensal bacteria

Nat Biotechnol. 2000 Oct;18(10):1060-4. doi: 10.1038/80250.

Abstract

Two recombinant strains of Streptococcus gordonii, secreting or displaying a microbicidal single-chain antibody (H6), and stably colonizing rat vagina, were used to treat an experimental vaginitis caused by Candida albicans. A post-challenge intravaginal delivery of the H6-secreting strain was as efficacious as fluconazole in rapidly abating the fungal burden. Three weeks after challenge, 75% and 37.5% of the rats treated with the H6-secreting or displaying bacteria, respectively, were cured of the infection, which persisted in 100% of the animals treated with a S. gordonii strain expressing an irrelevant single-chain antibody. Thus, a human commensal bacterium can be suitably engineered to locally release a therapeutic antibody fragment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intravaginal
  • Animals
  • Anti-Bacterial Agents
  • Anti-Infective Agents / administration & dosage
  • Anti-Infective Agents / immunology
  • Anti-Infective Agents / therapeutic use
  • Antifungal Agents / pharmacology
  • Antifungal Agents / therapeutic use
  • Candida albicans / drug effects
  • Candida albicans / immunology*
  • Candida albicans / physiology
  • Candidiasis / immunology
  • Candidiasis / microbiology
  • Candidiasis / therapy*
  • Colony Count, Microbial
  • Disease Models, Animal
  • Female
  • Fluconazole / pharmacology
  • Fluconazole / therapeutic use
  • Humans
  • Immunization, Passive
  • Immunoglobulin Idiotypes / administration & dosage
  • Immunoglobulin Idiotypes / genetics
  • Immunoglobulin Idiotypes / immunology*
  • Immunoglobulin Idiotypes / therapeutic use*
  • Mycotoxins / administration & dosage
  • Mycotoxins / chemistry
  • Mycotoxins / immunology
  • Mycotoxins / therapeutic use
  • Protein Engineering
  • Rats
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / genetics
  • Recombinant Proteins / immunology
  • Recombinant Proteins / therapeutic use
  • Streptococcus / cytology
  • Streptococcus / genetics*
  • Streptococcus / physiology
  • Vaginitis / immunology
  • Vaginitis / microbiology
  • Vaginitis / therapy*

Substances

  • Anti-Bacterial Agents
  • Anti-Infective Agents
  • Antifungal Agents
  • Immunoglobulin Idiotypes
  • Mycotoxins
  • Recombinant Proteins
  • Fluconazole