Monoclonal antibodies to Cryptococcus neoformans glucuronoxylomannan enhance fluconazole efficacy

J. Mukherjee, M. Feldmesser, M. D. Scharff, Arturo Casadevall

Research output: Contribution to journalArticle

Abstract

Monoclonal antibody (MAb) 2H1, which binds to the capsular glucuronoxylomannan (GXM) of the fungus Cryptococcus neoformans, prolonged survival and decreased fungal burden in an experimental routine infection. Fluconazole (FLU) is a triazole antibiotic which is effective against C. neoformans. The efficacy of MAb 2H1 in combination with FLU was studied in vitro with the murine macrophage-like cell line J7741.16 and in vivo in mice infected intravenously. In vitro, the combination of MAb 2H1 and FLU was more effective than either agent alone in reducing the number of CFU of C. neoformans cocultured with J774.16 cells. In combination with FLU, GXM- binding MAbs of the immunoglobulin M (IgM), IgG1, IgG2a, IgG2b, IgG3, and IgA isotypes were effective in reducing the numbers of CFU in C. neoformans- J774.16 cocultures. For the in vivo experiments, A/JCr mice were infected intravenously with 5 x 105 organisms treated with MAb and FLU. The therapeutic effect of MAb 2H1 was primarily to reduce the number of CFU in the lung and the serum GXM level, whereas FLU was most effective in reducing the number of CFU in the brain. Mice receiving combination therapy had lower numbers of CFU in the lung and serum GXM levels than mice treated with FLU alone. Administration of MAb 2H1 with or without FLU had little or no effect on the number of CFU in the brain. The results provide support for combined therapy.

Original languageEnglish (US)
Pages (from-to)1398-1405
Number of pages8
JournalAntimicrobial Agents and Chemotherapy
Volume39
Issue number7
StatePublished - 1995
Externally publishedYes

Fingerprint

Cryptococcus neoformans
Fluconazole
Monoclonal Antibodies
Immunoglobulin G
Lung
Triazoles
glucuronoxylomannan
Brain
Therapeutic Uses
Coculture Techniques
Serum
Immunoglobulin A
Immunoglobulin M
Fungi
Macrophages
Anti-Bacterial Agents
Cell Line
Therapeutics
Infection

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

Monoclonal antibodies to Cryptococcus neoformans glucuronoxylomannan enhance fluconazole efficacy. / Mukherjee, J.; Feldmesser, M.; Scharff, M. D.; Casadevall, Arturo.

In: Antimicrobial Agents and Chemotherapy, Vol. 39, No. 7, 1995, p. 1398-1405.

Research output: Contribution to journalArticle

@article{def6ebfca37641b3b2a80aa3dafe973a,
title = "Monoclonal antibodies to Cryptococcus neoformans glucuronoxylomannan enhance fluconazole efficacy",
abstract = "Monoclonal antibody (MAb) 2H1, which binds to the capsular glucuronoxylomannan (GXM) of the fungus Cryptococcus neoformans, prolonged survival and decreased fungal burden in an experimental routine infection. Fluconazole (FLU) is a triazole antibiotic which is effective against C. neoformans. The efficacy of MAb 2H1 in combination with FLU was studied in vitro with the murine macrophage-like cell line J7741.16 and in vivo in mice infected intravenously. In vitro, the combination of MAb 2H1 and FLU was more effective than either agent alone in reducing the number of CFU of C. neoformans cocultured with J774.16 cells. In combination with FLU, GXM- binding MAbs of the immunoglobulin M (IgM), IgG1, IgG2a, IgG2b, IgG3, and IgA isotypes were effective in reducing the numbers of CFU in C. neoformans- J774.16 cocultures. For the in vivo experiments, A/JCr mice were infected intravenously with 5 x 105 organisms treated with MAb and FLU. The therapeutic effect of MAb 2H1 was primarily to reduce the number of CFU in the lung and the serum GXM level, whereas FLU was most effective in reducing the number of CFU in the brain. Mice receiving combination therapy had lower numbers of CFU in the lung and serum GXM levels than mice treated with FLU alone. Administration of MAb 2H1 with or without FLU had little or no effect on the number of CFU in the brain. The results provide support for combined therapy.",
author = "J. Mukherjee and M. Feldmesser and Scharff, {M. D.} and Arturo Casadevall",
year = "1995",
language = "English (US)",
volume = "39",
pages = "1398--1405",
journal = "Antimicrobial Agents and Chemotherapy",
issn = "0066-4804",
publisher = "American Society for Microbiology",
number = "7",

}

TY - JOUR

T1 - Monoclonal antibodies to Cryptococcus neoformans glucuronoxylomannan enhance fluconazole efficacy

AU - Mukherjee, J.

AU - Feldmesser, M.

AU - Scharff, M. D.

AU - Casadevall, Arturo

PY - 1995

Y1 - 1995

N2 - Monoclonal antibody (MAb) 2H1, which binds to the capsular glucuronoxylomannan (GXM) of the fungus Cryptococcus neoformans, prolonged survival and decreased fungal burden in an experimental routine infection. Fluconazole (FLU) is a triazole antibiotic which is effective against C. neoformans. The efficacy of MAb 2H1 in combination with FLU was studied in vitro with the murine macrophage-like cell line J7741.16 and in vivo in mice infected intravenously. In vitro, the combination of MAb 2H1 and FLU was more effective than either agent alone in reducing the number of CFU of C. neoformans cocultured with J774.16 cells. In combination with FLU, GXM- binding MAbs of the immunoglobulin M (IgM), IgG1, IgG2a, IgG2b, IgG3, and IgA isotypes were effective in reducing the numbers of CFU in C. neoformans- J774.16 cocultures. For the in vivo experiments, A/JCr mice were infected intravenously with 5 x 105 organisms treated with MAb and FLU. The therapeutic effect of MAb 2H1 was primarily to reduce the number of CFU in the lung and the serum GXM level, whereas FLU was most effective in reducing the number of CFU in the brain. Mice receiving combination therapy had lower numbers of CFU in the lung and serum GXM levels than mice treated with FLU alone. Administration of MAb 2H1 with or without FLU had little or no effect on the number of CFU in the brain. The results provide support for combined therapy.

AB - Monoclonal antibody (MAb) 2H1, which binds to the capsular glucuronoxylomannan (GXM) of the fungus Cryptococcus neoformans, prolonged survival and decreased fungal burden in an experimental routine infection. Fluconazole (FLU) is a triazole antibiotic which is effective against C. neoformans. The efficacy of MAb 2H1 in combination with FLU was studied in vitro with the murine macrophage-like cell line J7741.16 and in vivo in mice infected intravenously. In vitro, the combination of MAb 2H1 and FLU was more effective than either agent alone in reducing the number of CFU of C. neoformans cocultured with J774.16 cells. In combination with FLU, GXM- binding MAbs of the immunoglobulin M (IgM), IgG1, IgG2a, IgG2b, IgG3, and IgA isotypes were effective in reducing the numbers of CFU in C. neoformans- J774.16 cocultures. For the in vivo experiments, A/JCr mice were infected intravenously with 5 x 105 organisms treated with MAb and FLU. The therapeutic effect of MAb 2H1 was primarily to reduce the number of CFU in the lung and the serum GXM level, whereas FLU was most effective in reducing the number of CFU in the brain. Mice receiving combination therapy had lower numbers of CFU in the lung and serum GXM levels than mice treated with FLU alone. Administration of MAb 2H1 with or without FLU had little or no effect on the number of CFU in the brain. The results provide support for combined therapy.

UR - http://www.scopus.com/inward/record.url?scp=0029077577&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029077577&partnerID=8YFLogxK

M3 - Article

C2 - 7492075

AN - SCOPUS:0029077577

VL - 39

SP - 1398

EP - 1405

JO - Antimicrobial Agents and Chemotherapy

JF - Antimicrobial Agents and Chemotherapy

SN - 0066-4804

IS - 7

ER -