IMMUNOGLOBULIN G3 BLOCKING ANTIBODIES TO THE FUNGAL PATHOGEN CRYPTOCOCCUS-NEOFORMANS

Vaccination and infection can elicit protective and nonprotective anti bodies to the: fungus Cryptococcus neoformans in mice. The effect of n onprotective antibodies on host defense is unknown. In this study we u sed mixtures of protective and nonprotective monoclonal antibodies (mA bs) to determine if nonprotective mAbs blocked the activity of the pro tective mAbs. Antibody isotype and epitope specificity are important i n determining the ability to prolong survival in mice given a lethal C . neoformans infection. Three different nonprotective immunoglobulin ( Ig) G3 mAbs to cryptococcal capsular polysaccharide were used to study the interaction between the IgG3 isotype and protective IgG1 and IgG2 a mAbs in murine cryptococcal infection. One IgG3 mAb reduced the prot ective efficacy of an IgG1 with identical epitope specificity. A secon d IgG3 mAb with different epitope specificity also reduced the protect ion provided by the IgG1 mAb. The protective efficacy of an IgG2a mAb was also dramatically decreased by still another IgG3 mAb. To our know ledge this is the first report of blocking antibodies to a fungal path ogen. The results have important implications for the development of v accines and passive antibody therapy against C. neoformans.