Preliminary Assessment of a Human Recombinant Antibody Fragment to hsp90 in Murine Invasive Candidiasis

Matthews, Ruth; Hodgetts, Samantha; Burnie, James

doi:10.1093/infdis/171.6.1668

Cited by 101 publications

(68 citation statements)

References 14 publications

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“…Studies by Cutler and collaborators demonstrated that the protective murine antimannan IgM antibody B6.1 enhances mouse neutrophil candidacidal activity in the presence of normal mouse serum (5) and that protection by B6.1 or its murine IgG3 variant requires an intact complement system (14). However, antibody-mediated protection against systemic candidiasis has also been observed with a recombinant human antibody fragment specific for heat shock protein 90 (HSP90) that is free of the Fc region (27,29). The protective mechanism for the Fcfree anti-HSP90 fragment has not been completely understood (29).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2006

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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.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2006

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“…From our results, Aflmp1p was shown to be closely associated with humoral immunity, and antibodies have been suggested to be important against certain extracellular opportunistic fungi (6,13,14); immunization could be administered through the mucosal route to stimulate the production of secretory immuno- …”

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confidence: 69%

AFLMP1 Encodes an Antigenic Cell Wall Protein in Aspergillus flavus

et al. 2003

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We have previously reported the cloning and characterization of the MP1 gene in Penicillium marneffei and the AFMP1 gene in Aspergillus fumigatus and their use for serodiagnosis of penicilliosis and aspergilloma and invasive aspergillosis, respectively. In this study, we describe the cloning of the AFLMP1 gene, which encodes the homologous antigenic cell wall protein in Aspergillus flavus, the most common Aspergillus species associated with human disease in our locality and in other Asian countries and the second most common Aspergillus species associated with human disease in Western countries. AFLMP1 codes for a protein, Aflmp1p, of 273 amino acid residues, with a few sequence features that are present in Mp1p and Afmp1p, the homologous antigenic cell wall proteins in P. marneffei and A. fumigatus, respectively, as well as several other cell wall proteins of Saccharomyces cerevisiae and Candida albicans. It contains a serine-and threonine-rich region for O glycosylation, a signal peptide, and a putative glycosylphosphatidylinositol attachment signal sequence. Specific anti-Aflmp1p antibody was generated with recombinant Aflmp1p protein purified from Escherichia coli to allow further characterization of Aflmp1p. Indirect immunofluorescence analysis indicated that Aflmp1p is present on the surface of the hyphae of A. flavus. Finally, it was observed that patients with aspergilloma and invasive aspergillosis due to A. flavus develop a specific antibody response against Aflmp1p. This suggested that the recombinant protein and its antibody may be useful for serodiagnosis in patients with aspergilloma or invasive aspergillosis, and the protein may represent a good cell surface target for host humoral immunity.

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“…Mannoproteins have been implicated both in the activation of nonspecific immunity (24,27,33) and in the elicitation of cell-mediated immunity (19,30), and on the basis of our results, they may also be closely associated with humoral immunity. Antibodies have been suggested to be an important defense against certain extracellular opportunistic fungi (7,16,17). It has been shown that antibodies against the mannan of C. albicans protect against intravenously injected C. albicans cells (10).…”

Section: Discussionmentioning

confidence: 99%

Characterization of AFMP1 : a Novel Target for Serodiagnosis of Aspergillosis

Yuen

Chan

et al. 2001

J Clin Microbiol

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We cloned the AFMP1 gene, which encodes the first antigenic cell wall galactomannoprotein in Aspergillus fumigatus. AFMP1 codes for a protein, Afmp1p, of 284 amino acid residues, with a few sequence features that are present in Mp1p, the antigenic cell wall mannoprotein in Penicillium marneffei that we described previously, as well as several other cell wall proteins of Saccharomyces cerevisiae and Candida albicans. It contains a serineand threonine-rich region for O glycosylation, a signal peptide, and a putative glycosylphosphatidyl inositol attachment signal sequence. Specific anti-Afmp1p antibody was generated with recombinant Afmp1p protein purified from Escherichia coli to allow further characterization of Afmp1p. Afmp1p has a high affinity for Galanthus nivalis agglutinin, a characteristic indicative of a mannoprotein. Furthermore, it was recognized by a rat monoclonal antibody against the galactofuran side chain of galactomannan, indicating that it is a galactomannoprotein. Ultrastructural analysis by immunogold staining indicated that Afmp1p is present in the cell walls of the hyphae and conidia of A. fumigatus. Finally, it was observed that patients with aspergilloma and invasive aspergillosis due to A. fumigatus develop a specific antibody response against Afmp1p. This suggested that the recombinant protein and its antibody may be useful for serodiagnosis in patients with aspergilloma or invasive aspergillosis, and the protein may represent a good cell surface target for host humoral immunity.Since the last decade, Aspergillus spp. have been gaining prominence as opportunistic pathogens. In immunocompetent hosts, Aspergillus spp. rarely causes serious illnesses except for aspergilloma in patients with preexisting chronic lung diseases. On the other hand, invasive aspergillosis is one of the most important infectious causes of mortality in patients with hematological malignancies and bone marrow transplant (BMT) recipients, with an incidence of 6% in our recent study with 230 BMT recipients (35). Furthermore, up to 2.5% of solid organ transplant recipients, 12% of patients with AIDS, and 40% of patients with chronic granulomatous disease could be affected by this infection (12). The mortality rate in patients with invasive aspergillosis with pulmonary involvement and persistent neutropenia was 95% (8). Of all the known Aspergillus spp., Aspergillus fumigatus is the most common species associated with human disease.The successful management of invasive aspergillosis is hampered by difficulties in establishing a diagnosis. The "gold standard" for making a diagnosis is to obtain a positive culture of A. fumigatus and to demonstrate histological evidence of mycelial invasion from tissue specimens obtained by biopsy. Due to the very sick nature of these patients and often the presence of bleeding diathesis, tissue biopsy is often not possible or acceptable by patients. Although commercial kits for antigen detection assays with a monoclonal antibody against the galactomannan antigen extract are available for...

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Preliminary Assessment of a Human Recombinant Antibody Fragment to hsp90 in Murine Invasive Candidiasis

Cited by 101 publications

References 14 publications

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

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

AFLMP1 Encodes an Antigenic Cell Wall Protein in Aspergillus flavus

Characterization of AFMP1 : a Novel Target for Serodiagnosis of Aspergillosis

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