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Infection and Immunity, January 2006, p. 362-369, Vol. 74, No. 1
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.1.362-369.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Human Recombinant Antimannan Immunoglobulin G1 Antibody Confers Resistance to Hematogenously Disseminated Candidiasis in Mice

Mason X. Zhang,1* M. Charlotte Bohlman,2 Carol Itatani,1 Dennis R. Burton,3 Paul W. H. I. Parren,3,{dagger} Stephen C. St. Jeor,2 and Thomas R. Kozel2

Department of Biological Sciences, California State University, Long Beach, California 90840,1 Department of Microbiology and Immunology, University of Nevada School of Medicine, Reno, Nevada 89557,2 Departments of Immunology and Molecular Biology, The Scripps Research Institute, La Jolla, California 920373

Received 11 August 2005/ Returned for modification 21 September 2005/ Accepted 8 October 2005

Mannan is a major cell wall component found in Candida species. Natural antimannan antibody is present in sera from most normal adults, but its role in host resistance to hematogenously disseminated candidiasis is unknown. The purpose of this study was to develop recombinant human antimannan antibody and to study its protective function. A phage Fab display combinatorial library containing Fab genes from bone marrow lymphocytes was screened with Candida albicans yeast cells and chemically purified mannan. One antimannan Fab, termed M1, was converted to a full-length immunoglobulin G1 antibody, M1g1, and M1g1 was produced in CHO cells. The M1g1 epitope was found in C. albicans serotypes A and B, Candida tropicalis, Candida guilliermondii, Candida glabrata, and Candida parapsilosis. Its expression was active at both 23°C and 37°C and uniform over the cell surface. BALB/c mice passively immunized with M1g1 were more resistant than control mice to a lethal hematogenous infection by C. albicans, as evidenced by extension of survival in an M1g1 dose-dependent manner (P, 0.08 to <0.001) and by reduction in number of infection foci and their size in the kidney. In vitro studies found that M1g1 promoted phagocytosis and phagocytic killing of C. albicans yeast cells by mouse peritoneal macrophages and was required for activation of the mouse complement cascade. Thus, human antimannan antibody may have a protective role in host resistance to systemic candidiasis.

* Corresponding author. Mailing address: Department of Biological Sciences, California State University—Long Beach, 1250 Bellflower Blvd., Long Beach, CA 90840. Phone: (562) 985-4819. Fax: (562) 985-8878. E-mail: mzhang2{at}csulb.edu.

Editor: A. Casadevall

{dagger} Present address: Genmab B.V., Utrecht, The Netherlands.

Infection and Immunity, January 2006, p. 362-369, Vol. 74, No. 1
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.1.362-369.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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