TY - JOUR
T1 - A human IgM monoclonal antibody prolongs survival of mice with lethal cryptococcosis
AU - Fleuridor, Richardson
AU - Zhong, Zhaojing
AU - Pirofski, Liise Anne
N1 - Funding Information:
Received 21 April 1998; revised 3 June 1998. Presented in part: 97th meeting of the American Society for Microbiology, 5 May 1997, Miami (abstract E51); 98th meeting of the American Society for Microbiology, 18 May 1998, Atlanta (abstract F20). Sera were obtained with informed consent of the donors, according to human experimentation guidelines of the US Department of Health and Human Services. Animal experimentation was carried out in accordance with the guidelines of Animal Institute of the Albert Einstein College of Medicine. Financial support: NIH (AI-35370 to L.P. and NS-070S8 to R.F.). Reprints or correspondence: Dr. Liise-anne Pirofski, Division of Infectious Diseases, Room 402 Forchheimer Bldg., Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461 (pirofski@aecom.yu.edu).
PY - 1998
Y1 - 1998
N2 - 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 V(H)1, V(H)3, and V(H)4 gene segments. Antibodies to GXM were shown to use V(H)3 gene segments, and antibodies with the greatest binding to GXM also bound to protein A. A V(H)3-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.
AB - 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 V(H)1, V(H)3, and V(H)4 gene segments. Antibodies to GXM were shown to use V(H)3 gene segments, and antibodies with the greatest binding to GXM also bound to protein A. A V(H)3-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.
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U2 - 10.1086/515688
DO - 10.1086/515688
M3 - Article
C2 - 9806064
AN - SCOPUS:0031716168
VL - 178
SP - 1213
EP - 1216
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
SN - 0022-1899
IS - 4
ER -