Preliminary assessment of a human recombinant antibody fragment to hsp90 in murine invasive candidiasis.
Seroconversion to hsp90 is associated with recovery from systemic candidiasis in humans, and a murine monoclonal antibody to this hsp90 antigen (LKVIRK epitope) was protective in mice. A human recombinant antibody to the same epitope was assessed in acute and chronic models of murine invasive candidiasis. Lethal intravenous challenge with fluconazole-susceptible (strain 4) or fluconazole-resistant (strain 019) Candida albicans, followed 2 h later by a single dose of recombinant antibody, was associated with a statistically significant drop in mortality of > or = 40% (two experiments in BALB/c mice given strain 4; one experiment in CD-1 mice given strain 019) or 23% (BALB/c mice, strain 019). In mice sublethally infected with strain 4, treatment with recombinant antibody was associated with improved renal clearance of infection. Antibody-mediated protection may involve neutralization of the protein-binding properties of circulating candidal hsp90, since LKVIRK strongly bound dexamethasone in vitro.
Matthews
R
R
Department of Medical Microbiology, University of Manchester Medical School, United Kingdom.
Hodgetts
S
S
Burnie
J
J
D000595:Amino Acid Sequence; D000818:Animals; D002176:Candida albicans; D002177:Candidiasis / Q000628:therapy*; D000939:Epitopes; D005260:Female; D018841:HSP90 Heat-Shock Proteins / Q000276:immunology*; D006801:Humans; D007116:Immunization, Passive; D007167:Immunotherapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology
D000939:Epitopes; D018841:HSP90 Heat-Shock Proteins; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic