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
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Research Support, Non-U.S. Gov't
MeSH terms
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Administration, Intravaginal
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Animals
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Anti-Bacterial Agents
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Anti-Infective Agents / administration & dosage
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Anti-Infective Agents / immunology
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Anti-Infective Agents / therapeutic use
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Antifungal Agents / pharmacology
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Antifungal Agents / therapeutic use
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Candida albicans / drug effects
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Candida albicans / immunology*
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Candida albicans / physiology
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Candidiasis / immunology
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Candidiasis / microbiology
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Candidiasis / therapy*
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Colony Count, Microbial
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Disease Models, Animal
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Female
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Fluconazole / pharmacology
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Fluconazole / therapeutic use
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Humans
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Immunization, Passive
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Immunoglobulin Idiotypes / administration & dosage
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Immunoglobulin Idiotypes / genetics
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Immunoglobulin Idiotypes / immunology*
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Immunoglobulin Idiotypes / therapeutic use*
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Mycotoxins / administration & dosage
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Mycotoxins / chemistry
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Mycotoxins / immunology
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Mycotoxins / therapeutic use
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Protein Engineering
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Rats
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Recombinant Proteins / administration & dosage
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Recombinant Proteins / genetics
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Recombinant Proteins / immunology
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Recombinant Proteins / therapeutic use
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Streptococcus / cytology
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Streptococcus / genetics*
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Streptococcus / physiology
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Vaginitis / immunology
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Vaginitis / microbiology
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Vaginitis / therapy*
Substances
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Anti-Bacterial Agents
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Anti-Infective Agents
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Antifungal Agents
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Immunoglobulin Idiotypes
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Mycotoxins
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Recombinant Proteins
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Fluconazole