Molecular characterization of a Dirofilaria immitis cDNA encoding a highly immunoreactive antigen

Culpepper, Janice; Grieve, Robert B.; Friedman, Lori S.; Mika-Grieve, Marcia; Frank, Glenn; Dale, Beverly A.

doi:10.1016/0166-6851(92)90094-z

Cited by 47 publications

(39 citation statements)

References 20 publications

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“…This is the case for the genes encoding NPAs of other nematodes, such as Dirofilaria immitis (6), Brugia pahangi (27), Brugia malayi (27), and D. viviparus (1). The nOPA antigen was located in the intestinal cells of Ostertagia L3 and in the cuticle and hypodermis of L4 and adult parasites.…”

Section: Discussionmentioning

confidence: 99%

“…Although NPAs (especially ABA-1 from Ascaris) have been characterized in detail biochemically and molecularly (1,3,6,21,22,32,33), to our knowledge they have never been tested as vaccines in protection trials. Interestingly, allergens (by definition) induce an immunoglobulin E (IgE) antibody response that leads to a type I hypersensitivity reaction similar to the reaction which appears to be associated with protective immune responses to helminth parasites (20).…”

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confidence: 99%

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Vaccination with anOstertagia ostertagiPolyprotein Allergen Protects Calves against Homologous Challenge Infection

Vercauteren¹,

Geldhof²,

Vercruysse³

et al. 2004

Infect Immun

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As an alternative to antihelminthic drugs, we are exploiting vaccination to control infections with the abomasal nematode Ostertagia ostertagi in cattle. Our focus for vaccine targets is excretory-secretory (ES) products of this parasite. One of the most abundant antigens in larval and adult Ostertagia ES products is a protein homologous to nematode polyprotein allergens. We found that the Ostertagia polyprotein allergen (OPA) is encoded by a single-copy gene. OPA comprises three or more repeated units, and only the 15-kDa subunits are found in ES products. The native antigen is localized in the intestinal cells of third-stage larvae and in the hypodermis and cuticle of fourth-stage larvae and adult parasites. Vaccination of cattle with native OPA (nOPA) in combination with QuilA resulted in protection against Ostertagia challenge infections. The geometric mean cumulative fecal egg counts in the nOPA-vaccinated animals were reduced by 60% compared to the counts in the control group during the 2-month course of the experiment. Both male and female adult worms in nOPA-vaccinated animals were significantly shorter than the worms in the control animals. In the abomasal mucus of vaccinated animals the nOPA-specific immunoglobulin G1 (IgG1) and IgG2 levels were significantly elevated compared to the levels in the control animals. Reductions in the Ostertagia egg output and the length of the adult parasites were significantly correlated with IgG1 levels. IgG2 titers were only negatively associated with adult worm length. Protected animals showed no accumulation of effector cells (mast cells, globular leukocytes, and eosinophils) in the mucosa. In contrast to the native antigen, recombinant OPA expressed in Escherichia coli did not stimulate any protection.At present, the control of Ostertagia ostertagi infections in cattle largely depends on the use of chemical antihelminthic drugs. Residues of introduced chemicals in foodstuffs and the environment have become a serious consumer concern. Reports of resistance to antiparasitic drugs for a closely related parasite, Cooperia species, in cattle (5, 31) make the development of alternative control systems even more urgent.Early attempts to protect cattle against the abomasal nematode O. ostertagi with irradiated larval vaccines (2) or with crude somatic (12) and excretory-secretory (ES) products (13) were not successful. Moderate levels of protection were obtained in calves immunized with gut membrane glycoproteins of O. ostertagi (24). Recently, it was shown that vaccination of cattle with ES products of adult Ostertagia worms enriched for cysteine proteinases by thiol-Sepharose chromatography reduced the fecal egg counts by 60% compared to the counts in the control group (11).Generally, ES products are considered to be essential for the development and survival of the parasite within the host and are targets for vaccine development (17). Immunoscreening of cDNA libraries of both larvae (third-stage larvae [L3] and L4)

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Vaccination with anOstertagia ostertagiPolyprotein Allergen Protects Calves against Homologous Challenge Infection

Vercauteren¹,

Geldhof²,

Vercruysse³

et al. 2004

Infect Immun

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“…Neither of these are full-length, both having arisen by internal priming of the mRNA in firststrand cDNA synthesis, presumably due to the high frequency of adenine residues within the coding region. This was, however, fortuitious given that the full-length mRNA encoding the ABA-1 polyprotein, and that from other species, is variously estimated or known to contain between 10 and 20 units [11][12][13]15], which would amount to a transcript of such a size that complete copies are unlikely to be represented in the cDNA library ; similar difficulties have prevented the complete sequencing of any filaggrin cDNA to date [6][7][8][9]. Translation of the open reading Fluorescence spectra were recorded with approx.…”

Section: Results and Discussion Cdna Cloning And Sequence Analysismentioning

confidence: 99%

“…These are the polyprotein allergen proteins of nematodes (NPAs) which bind fatty acids and retinol [11][12][13][14][15][16][17][18]. Some NPAs exhibit dramatic differences in the sequences of the repeated units, although each possesses conserved signature amino acid positions [15,16].…”

Section: Introductionmentioning

confidence: 99%

“…To date, the ligand-binding characteristics of these proteins have been demonstrated only for single units of the polyprotein from a variety of nematode species, but not for two different units from the same polyprotein array. It therefore remains a possibility that the various members of the same array are functionally different in i o, which will be important, given that NPA proteins are secreted into the tissues inhabited by parasitic nematodes in humans and other hosts [11][12][13]15].…”

Section: Introductionmentioning

confidence: 99%

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Sequence-divergent units of the ABA-1 polyprotein array of the nematode Ascaris suum have similar fatty-acid- and retinol-binding properties but different binding-site environments

Moore

McDermott

Price

et al. 1999

Biochemical Journal

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Polyproteins comprise long polypeptides that are posttranslationally cleaved into proteins of different function, or tandemly repetitive polypeptides which are processed into multiple versions of proteins which are presumed to have the same function. In the latter case the individual units of the polyprotein can differ substantially in sequence. Identity of function between the different units therefore cannot be assumed. Here we have examined the ABA-1 polyprotein allergen of the parasitic nematode Ascaris suum and found it to contain units which show a 50 % difference in amino acid sequence. The parasite therefore produces at least two radically different forms of the allergen encoded within the polyprotein array. In fluorescence-based ligand-binding assays, recombinant polypeptides representing the two forms (designated ABA-1A1 and ABA-1B1) showed similar binding affinities for a range of fluorescent active-site probes [retinol, dansylundecanoic acid, dansyl--α-amino-

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Vaccine Research and Development for the Prevention of Filarial Nematode Infections

Grieve¹,

Wisnewski²,

Frank³

et al. 1995

Vaccine Design

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Molecular characterization of a Dirofilaria immitis cDNA encoding a highly immunoreactive antigen

Cited by 47 publications

References 20 publications

Vaccination with anOstertagia ostertagiPolyprotein Allergen Protects Calves against Homologous Challenge Infection

Vaccination with anOstertagia ostertagiPolyprotein Allergen Protects Calves against Homologous Challenge Infection

Sequence-divergent units of the ABA-1 polyprotein array of the nematode Ascaris suum have similar fatty-acid- and retinol-binding properties but different binding-site environments

Vaccine Research and Development for the Prevention of Filarial Nematode Infections

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