PRELIMINARY ASSESSMENT OF A HUMAN RECOMBINANT ANTIBODY FRAGMENT TO HSP90 IN MURINE INVASIVE CANDIDIASIS

Seroconversion to hsp90 is associated with recovery from systemic cand idiasis in humans, and a murine monoclonal antibody to this hsp90 anti gen (LKVIRK epitope) was protective in mice, A human recombinant antib ody to the same epitope was assessed in acute and chronic models of mu rine invasive candidiasis. Lethal intravenous challenge with fluconazo le-susceptible (strain 4) or fluconazole-resistant (strain 019) Candid a albicans, followed 2 h later by a single dose of recombinant antibod y, was associated with a statistically significant drop in mortality o f greater than or equal to 40% (two experiments in BALB/c mice given s train 4; one experiment in CD-1 mice given strain 019) or 23% (BALB/c mice, strain 019). In mice sublethally infected with strain 4, treatme nt with recombinant antibody was associated with improved renal cleara nce of infection. Antibody-mediated protection may involve neutralizat ion of the protein-binding properties of circulating candidal hsp90, s ince LKVIRK strongly bound dexamethasone in vitro.