Therapy of mucosal candidiasis by expression of an anti-idiotype in human commensal bacteria.
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.
Beninati
C
C
Dipartimento di Biologia Molecolare/Microbiologia, Università degli Studi di Siena, Siena, Italy.
Oggioni
M R
MR
Boccanera
M
M
Spinosa
M R
MR
Maggi
T
T
Conti
S
S
Magliani
W
W
De Bernardis
F
F
Teti
G
G
Cassone
A
A
Pozzi
G
G
Polonelli
L
L
D000282:Administration, Intravaginal; D000818:Animals; D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D000935:Antifungal Agents / Q000494:pharmacology / Q000627:therapeutic use; D002176:Candida albicans / Q000187:drug effects / Q000276:immunology* / Q000502:physiology; D002177:Candidiasis / Q000276:immunology / Q000382:microbiology / Q000628:therapy*; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D005260:Female; D015725:Fluconazole / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007116:Immunization, Passive; D007130:Immunoglobulin Idiotypes / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use*; D009183:Mycotoxins / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use; D015202:Protein Engineering; D051381:Rats; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D013291:Streptococcus / Q000166:cytology / Q000235:genetics* / Q000502:physiology; D014627:Vaginitis / Q000276:immunology / Q000382:microbiology / Q000628:therapy*
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D000935:Antifungal Agents; D007130:Immunoglobulin Idiotypes; D009183:Mycotoxins; D011994:Recombinant Proteins; D015725:Fluconazole