A cloned gene of Cryptosporidium parvum encodes neutralization-sensitive epitopes

Perryman, Lance E.; Jasmer, Douglas P.; Riggs, Michael W.; Bohnet, Stewart; McGuire, Travis C.; Arrowood, Michael J.

doi:10.1016/0166-6851(96)02681-3

Cited by 88 publications

(61 citation statements)

References 47 publications

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“…The neutralizing monoclonal antibodies 7D10 and C6B6, which were first used to identify p23, are directed at linear (QDKPAD) and conformational epitopes, respectively, in the C-terminal region of p23. 11 Sturbaum and others reported that 9 of 10 monoclonal antibodies generated against C. parvum p23 were reactive with the p23 antigen from three C. hominis isolates, confirming that for the most part p23 is antigenically conserved among isolates from both species. 17,45 However, the epitopes recognized by human serum antibodies to p23 remain to be determined.…”

Section: P23 Antibodies and Polymorphisms In Children With Cryptospormentioning

confidence: 78%

“…[11][12][13][14] Monoclonal and bovine colostral antibodies to p23 protect against Cryptosporidium parvum challenge in mice and calves, respectively. 11,12,[15][16][17][18] The p23 antigen induces serum, mucosal, humoral, and cell-mediated immune responses in experimentally infected or immunized animals, [19][20][21][22][23][24][25][26] and active immunization with DNA or peptide vaccines targeting p23 has been shown to confer varying degrees of protection in animal models. [27][28][29] The p23 antigen is one of the most immunodominant Cryptosporidium antigens and is consistently recognized by serum from actively infected or previously exposed humans.…”

Section: Introductionmentioning

confidence: 99%

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Systemic Antibody Responses to the Immunodominant p23 Antigen and p23 Polymorphisms in Children with Cryptosporidiosis in Bangladesh

Borad¹,

Allison²,

Wang³

et al. 2012

The American Society of Tropical Medicine and Hygiene

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Abstract. Cryptosporidium is a major cause of diarrhea in children in developing countries. However, there is no vaccine available and little is known about immune responses to protective antigens. We investigated antibody responses to p23, a putative vaccine candidate, in children in Bangladesh with cryptosporidiosis and diarrhea (cases) and uninfected children with diarrhea (controls), and p23 gene polymorphisms in infecting species. Serum IgM, IgG, and IgA responses to p23 were significantly greater in cases than controls after three weeks of follow-up. Cases with acute diarrhea had significantly greater serum IgA and IgM responses than those with persistent diarrhea, which suggested an association with protection from prolonged disease. The p23 sequences were relatively conserved among infecting species and subtype families. Although most children were infected with Cryptosporidium hominis, there was a cross-reactive antibody response to C. parvum antigen. These results support further development of p23 as a vaccine candidate.

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Section: P23 Antibodies and Polymorphisms In Children With Cryptospormentioning

confidence: 78%

Section: Introductionmentioning

confidence: 99%

Systemic Antibody Responses to the Immunodominant p23 Antigen and p23 Polymorphisms in Children with Cryptosporidiosis in Bangladesh

Borad¹,

Allison²,

Wang³

et al. 2012

The American Society of Tropical Medicine and Hygiene

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“…Of the multiple antigens recognized by 3E2, CSL was shown to be the critical surface-exposed species mechanistically bound by MAb to elicit the CSP-like reaction (39). The neutralizing activity of MAb 3E2 in vitro and its ability to passively protect against infection in vivo (19, 39) are profoundly greater than those of other MAbs we have produced against C. parvum (31,33,37,38,42). Therefore, MAb 3E2 was deemed an essential formulation candidate in the present study.…”

mentioning

confidence: 91%

“…The C. parvum antigens GP25-200 (1,39), CSL (39,40), and P23 (1,23) were selected as targets for the present study. Each antigen is involved in the pathogenesis of infection, expressed on the surface of both infective zoite stages, and conserved on diverse C. parvum isolates (1,23,31,39,40). GP25-200 was originally defined by MAb C4A1 as a sporozoite apical and surface pellicle glycoprotein complex comprised of multiple 25-to 200-kDa species identified in reducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) (1).…”

mentioning

confidence: 99%

Characterization and Formulation of Multiple Epitope-Specific Neutralizing Monoclonal Antibodies for Passive Immunization against Cryptosporidiosis

2000

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The coccidian parasite Cryptosporidium parvum causes diarrhea in humans, calves, and other mammals. Neither immunization nor parasite-specific pharmaceuticals that are consistently effective against this organism are available. While polyclonal antibodies against whole C. parvum reduce infection, their efficacy and predictability are suboptimal. We hypothesized that passive immunization against cryptosporidiosis could be improved by using neutralizing monoclonal antibodies (MAbs) targeting functionally defined antigens on the infective stages. We previously reported that the apical complex and surface-exposed zoite antigens CSL, GP25-200, and P23 are critical in the infection process and are therefore rational targets. In the present study, a panel of 126 MAbs generated against affinity-purified CSL, GP25-200, and P23 was characterized to identify the most efficacious neutralizing MAb formulation targeting each antigen. To identify neutralizing MAbs, sporozoite infectivity following exposure to individual MAbs was assessed by enzyme-linked immunosorbent assay. Of 126 MAbs evaluated, 47 had neutralizing activity. These were then evaluated individually in oocystchallenged neonatal mice, and 14 MAbs having highly significant efficacy were identified for further testing in formulations. Epitope specificity assays were performed to determine if candidate MAbs recognized the same or different epitopes.

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“…These proteins, as well as proteins on the surface of the zoite, facilitate attachment to the cell surface, gliding motility, and subsequent invasion and intracellular development of the parasite. However, unlike those of other apicomplexans, most of the Cryptosporidium surface and apical complex antigens that have been characterized are glycoproteins [9][10][11][12][13][14]. Two of these, gp900 [10] and gp40/15 [11,13,14], are mucin-like glycoproteins, proteins with high percentages of serine and threonine residues that are sites for O-linked glycosylation.…”

Section: Introductionmentioning

confidence: 99%

Stable expression of Cryptosporidium parvum glycoprotein gp40/15 in Toxoplasma gondii

O’Connor

Wanyiri

Wójczyk

et al. 2007

Molecular and Biochemical Parasitology

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Cryptosporidium is a cause of diarrheal disease worldwide. Parasite glycoproteins involved in invasion of Cryptosporidium into host cells have been investigated as possible targets for effective interventions against this parasite. One of these, Cpgp40/15, is expressed as a precursor protein that is cleaved by a parasite-derived furin-like protease activity into gp15, a glycophosphatidyl inositol anchored surface protein, and gp40, that associates with gp15 and binds to host cells. Investigation of the functions of these glycoproteins requires an expression system that can produce similar glycosylation patterns to the native antigens. Previous work demonstrated that Cpgp40/15 transiently expressed in T. gondii was appropriately localized and glycosylated. In this study, T. gondii stable transfectants expressing gp40/15, gp15, gp40 and hemagglutinin (HA) tagged gp40 were generated. T. gondii recombinant gp40HA and gp40/15 (recTggp40HA and recTggp40/15) were isolated from infected cells by HA affinity chromatography and Helix pomatia lectin affinity chromatography, respectively. Mass spectrometry confirmed that recTggp40-HA and native Cpgp40 were similarly glycosylated. Like native Cpgp40/15, recTggp40/15 could be cleaved into the gp40 and gp15 products by human furin or by a furin-like protease activity in T. gondii tachyzoite lysates. However, processing was inefficient in intact tachyzoites. Unlike the N-terminus of native Cpgp40/15, which appears to be processed following signal peptide cleavage, the N-terminus of recTggp40/15 began at the predicted signal sequence cleavage site, 11 amino acids upstream of the N-terminus of native Cpgp40. The ability to express and isolate appropriately glycosylated Cryptosporidium glycoproteins will enable further investigations into host-parasite interactions of this important pathogen.

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A cloned gene of Cryptosporidium parvum encodes neutralization-sensitive epitopes

Cited by 88 publications

References 47 publications

Systemic Antibody Responses to the Immunodominant p23 Antigen and p23 Polymorphisms in Children with Cryptosporidiosis in Bangladesh

Systemic Antibody Responses to the Immunodominant p23 Antigen and p23 Polymorphisms in Children with Cryptosporidiosis in Bangladesh

Characterization and Formulation of Multiple Epitope-Specific Neutralizing Monoclonal Antibodies for Passive Immunization against Cryptosporidiosis

Stable expression of Cryptosporidium parvum glycoprotein gp40/15 in Toxoplasma gondii

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