Inhibition of β-1,3-Glucan Synthase and Cell Growth of Cryptococcus species by Recombinant Single-chain Anti-idiotypic Antibodies

Abstract

Recombinant single-chain fragment variable (scFv) anti-idiotypic antibodies were produced to represent the internal image of a HM-1 killer toxin, which is characterized by a wide spectrum of anti-fungal activity through inhibiting beta-1,3-glucan synthase (GS). We examined if scFv antibodies are active against Cryptococcus species, a human pathogen of increasing medical importance. The anti-cryptococcal activity of scFv antibodies and HM-1 were assessed by MIC analysis for C. neoformans IFM 40215 and C. albidus NBRC 0612 cells. The scFv antibodies had strong anti-cryptococcal activity in vitro with IC50 at 1.07 x 10(-7) to 2.60 x 10(-7) M for C. neoformans and C. albidus. Furthermore, the scFv antibodies potentially inhibited GS of C. neoformans with IC50 at 1.27 x 10(-7) to 2.27 x 10(-7) M. Both the anti-fungal and anti-GS activities of the scFv antibodies were markedly neutralized by the monoclonal antibody that neutralizes HM-1 killer toxin.