Characterization of an immunodominant Onchocerca volvulus antigen with patient sera and a monoclonal antibody.

Lucius, Richard; Schulz‐Key, H.; Büttner, Dietrich W.; Kern, Andrea; Kaltmann, Brigitte; Prod'hon, Jacques; Seeber, Frank; Walter, Roland; Kc, Saxena; Diesfeld, Hans Jochen

doi:10.1084/jem.167.4.1505

Cited by 31 publications

(11 citation statements)

References 11 publications

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“…Aspartyl protease inhibitors have been employed in the serologic diagnosis of filarial nematode infections. Serum antibody specific for Ov33-3 was detected in patients infected with O. volvulus (25,35). Antibodies against Bm33 have been found in B. malayi-infected patients (12).…”

Section: Discussionmentioning

confidence: 99%

An Aspartyl Protease Inhibitor Orthologue Expressed byParelaphostrongylus tenuisIs Immunogenic in an Atypical Host

Duffy

MacAfee

Burt

et al. 2002

Clin Vaccine Immunol

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Parelaphostrongylus tenuis is a neurotropic nematode common in white-tailed deer (Odocoileus virginianus) of eastern North America. This parasite is the causative agent of a debilitating neurologic disease in atypical hosts, including domestic livestock. In order to identify proteins of potential significance in the host-parasite relationship, a cDNA library was produced from adult P. tenuis mRNA. Screening the library with antisera from infected red deer (Cervus elaphus elaphus) and immunized AO strain rats, we identified clones with sequence similarities to aspartyl protease inhibitors from several parasitic nematodes. Antibody that was generated against this recombinant protein of P. tenuis (Pt-API-1) detected the native protein in E/S products, in muscle and gonad, and on the surface of the cuticle of adult male and female P. tenuis. The native protein was detected in internal structures of first-stage (L1) and third-stage (L3) larvae. Reverse transcription-PCR confirmed expression of Pt-api-1 in L1, L3, and adult male and female worms. Expression of Pt-API-1 throughout the life cycle of P. tenuis suggests an essential function. Antibodies specific for recombinant Pt-API-1 were detected by enzyme-linked immunosorbent assay in sera from 12 red deer experimentally infected with P. tenuis. Antibodies were detected within 28 to 56 days postinfection. Responses were sustained or biphasic in animals with patent infections, consistent with expression of Pt-API-1 by L1. Our results are compatible with findings in other parasitic nematodes showing that aspartyl protease inhibitors are highly immunogenic.

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Section: Discussionmentioning

confidence: 99%

An Aspartyl Protease Inhibitor Orthologue Expressed byParelaphostrongylus tenuisIs Immunogenic in an Atypical Host

Duffy

MacAfee

Burt

et al. 2002

Clin Vaccine Immunol

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“…A minor protein observed by surface labelling adult B. malayi is Bm‐33, a 33 kDa protein with similarity to the aspartyl protease inhibitor gene family (51). The best characterized homologue is in O. volvulus , in which the immunodominant Ov‐33 antigen elicits strong antibody responses in 96% of patients (52); similarly, a high proportion of B. malay i‐infected patients express antibodies to Bm‐ API‐1, particularly of IgG1 and IgG4 isotypes (16). Functionally, Ov‐33 expressed in yeast shows inhibition of the aspartyl protease pepsin (53), and the presence of a 17‐amino acid putative signal peptide at the N ‐terminus of Ov‐33 and Bm‐33 indicates that the product may be secreted by the filariae.…”

Section: Adult Surface‐associated Proteinsmentioning

confidence: 99%

Immunological genomics of Brugia malayi: filarial genes implicated in immune evasion and protective immunity

Maizels

Blaxter

Scott

2001

Parasite Immunology

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Filarial nematodes are metazoan parasites with genome sizes of> 100 million base pairs, probably encoding 15 000-20 000 genes. Within this considerable gene complement, it seems likely that filariae have evolved a spectrum of immune evasion products which underpin their ability to live for many years within the human host. Moreover, no suitable vaccine currently exists for human filarial diseases, and few markers have yet been established for diagnostic use. In this review, we bring together biochemical and immunological data on prominent filarial proteins with the exciting new information provided by the Filarial Genome Project's expressed sequence tag (EST) database. In this discussion, we focus on those genes with the highest immunological profile, such as inhibitors of host enzymes, cytokine homologues and stage-specific surface proteins, as well as products associated with the mosquito-borne infective larva which offer the best opportunity for an anti-filarial vaccine. These gene products provide a fascinating glimpse of the molecular repertoire which helminth parasites have evolved to manipulate and evade the mammalian immune response.

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“…rOv17 was purified under nondenaturing conditions by affinity chromatography using Ni-NTA resin (Qiagen, Hilden, Germany) and dialyzed twice against PBS. The control protein, recombinant 33-kDa onchocystatin (rOv33), an O. volvulus protein with homologies to aspartic protease inhibitors (26), was expressed and purified under identical conditions. Because rOv17 and rOv33 were expressed in E. coli, the endotoxin contamination was evaluated by quantitative, chromogenic Limulus amebocyte lysate assay (BioWhittaker, Walkersville, MD).…”

Section: Cloning and Expression Of Recombinant Proteinsmentioning

confidence: 99%

Modulation of Human T Cell Responses and Macrophage Functions by Onchocystatin, a Secreted Protein of the Filarial NematodeOnchocerca volvulus

Schönemeyer¹,

Lucius²,

Sonnenburg³

et al. 2001

The Journal of Immunology

145

132

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Immune responses of individuals infected with filarial nematodes are characterized by a marked cellular hyporesponsiveness and a shift of the cytokine balance toward a Th2/Th3 response. This modulation of cellular immune responses is considered as an important mechanism to avoid inflammatory immune responses that could eliminate the parasites. We investigated the immunomodulatory potential of a secreted cysteine protease inhibitor (onchocystatin) of the human pathogenic filaria Onchocerca volvulus. Recombinant onchocystatin (rOv17), a biologically active cysteine protease inhibitor that inhibited among others the human cysteine proteases cathepsins L and S, suppressed the polyclonally stimulated and the Ag-driven proliferation of human PBMC. Stimulated as well as unstimulated PBMC in the presence of rOv17 produced significantly more IL-10, which was paralleled in some situations by a decrease of IL-12p40 and preceded by an increase of TNF-α. At the same time, rOv17 reduced the expression of HLA-DR proteins and of the costimulatory molecule CD86 on human monocytes. Neutralization of IL-10 by specific Abs restored the expression of HLA-DR and CD86, whereas the proliferative block remained unaffected. Depletion of monocytes from the PBMC reversed the rOv17-induced cellular hyporeactivity, indicating monocytes to be the target cells of immunomodulation. Therefore, onchocystatin has the potential to contribute to a state of cellular hyporesponsiveness and is a possible pathogenicity factor essential for the persistence of O. volvulus within its human host.

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Characterization of an immunodominant Onchocerca volvulus antigen with patient sera and a monoclonal antibody.

Cited by 31 publications

References 11 publications

An Aspartyl Protease Inhibitor Orthologue Expressed byParelaphostrongylus tenuisIs Immunogenic in an Atypical Host

An Aspartyl Protease Inhibitor Orthologue Expressed byParelaphostrongylus tenuisIs Immunogenic in an Atypical Host

Immunological genomics of Brugia malayi: filarial genes implicated in immune evasion and protective immunity

Modulation of Human T Cell Responses and Macrophage Functions by Onchocystatin, a Secreted Protein of the Filarial NematodeOnchocerca volvulus

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