A human IgM monoclonal antibody prolongs survival of mice with lethal cryptococcosis.
Antifungal therapy cannot eradicate Cryptococcus neoformans infections in immunosuppressed patient groups. Therefore, adjunctive antibody-based therapy is being considered to enhance host immune responses to C. neoformans. To characterize potentially protective reagents, the idiotypic repertoire of human antibodies to cryptococcal glucuronoxylomannan (GXM) elicited by the investigational conjugate vaccine GXM-tetanus toxoid was examined. The variable genes used by human antibodies to GXM were analyzed with an antigen-based ELISA and mouse monoclonal antibodies (MAbs) that recognize determinants of human VH1, VH3, and VH4 gene segments. Antibodies to GXM were shown to use VH3 gene segments, and antibodies with the greatest binding to GXM also bound to protein A. A VH3-positive human monoclonal IgM prolonged survival of C. neoformans-infected mice. This is the first report that a human antibody is protective against C. neoformans. These results suggest that human MAbs may have promise as therapeutic reagents against cryptococcosis.
Fleuridor
R
R
Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Zhong
Z
Z
Pirofski
L
L
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000627:therapeutic use*; D000908:Antibodies, Fungal / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D003453:Cryptococcosis / Q000188:drug therapy*; D005260:Female; D005657:Fungal Vaccines / Q000276:immunology; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000276:immunology; D007130:Immunoglobulin Idiotypes; D007075:Immunoglobulin M / Q000627:therapeutic use*; D007135:Immunoglobulin Variable Region / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D011134:Polysaccharides / Q000276:immunology*; D018074:Vaccines, Conjugate / Q000276:immunology
D000888:Antibodies, Anti-Idiotypic; D000908:Antibodies, Fungal; D000911:Antibodies, Monoclonal; D005657:Fungal Vaccines; D007143:Immunoglobulin Heavy Chains; D007130:Immunoglobulin Idiotypes; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region; D011134:Polysaccharides; D018074:Vaccines, Conjugate; C027478:glucuronoxylomannan