The nature and prospects for gut membrane proteins as vaccine candidates for Haemonchus contortus and other ruminant trichostrongyloids

Knox, David P.; Redmond, D. L.; Newlands, G. F. J.; Skuce, Philip; Pettit, D.; Smith, William D.

doi:10.1016/s0020-7519(03)00167-x

Cited by 132 publications

(100 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Vaccination and genetic resistance of hosts have been viewed as sustainable methods of parasite control. Substantial progress and results have been obtained by using several H. contortus antigens, such as native H11 and H-gal-GP, to stimulate efficient levels of protective immunity in sheep [20]. Nevertheless, no commercial vaccine is yet available.…”

Section: Introductionmentioning

confidence: 99%

Haemonchus contortus(Nematoda: Trichostrongylidae) infection in lambs elicits an unequivocal Th2 immune response

Nguyen²,

et al. 2006

View full text Add to dashboard Cite

-Selection of resistant animals and host immunization have been proposed as alternative methods for the control of gastrointestinal nematode parasites. However, a better knowledge of the mechanisms involved in protective immunity against these parasites is required for the development of optimal strategies. In this study, 3 month old INRA 401 lambs (n = 81) were allocated into three groups: uninfected control, challenged either once (primary-infected animals) or twice (previouslyinfected animals) with 10 000 Haemonchus contortus L 3 . Uninfected control and challenged animals were sequentially sacrificed at 3, 7, 15 and 28 days post challenge. In both challenged groups, a clear Th 2 -oriented immune response was observed in the abomasal lymph node and mucosa. IL-4 and IL-13 mRNA over-expression, recruitment of eosinophils, mast cells and globule leukocytes and production of specific systemic IgG and mucosal IgA were observed earlier in previously-infected animals than in primary-infected ones. At 28 days post infection, no differences between intensities of these responses were observed between the challenged groups. Worm establishment rates were similar in previously-infected and primary-infected lambs. However, reductions of worm development, female fecundity and fecal egg output were observed in previously-infected sheep. We conclude that H. contortus infection in young INRA 401 lambs induced an unequivocal Th 2 immune response resulting in the regulation of worm egg production without affecting their establishment.Haemonchus contortus / sheep / Th 2 immune response / quantitative PCR / antibody and cellular response

show abstract

Section: Introductionmentioning

confidence: 99%

Haemonchus contortus(Nematoda: Trichostrongylidae) infection in lambs elicits an unequivocal Th2 immune response

Nguyen²,

et al. 2006

View full text Add to dashboard Cite

show abstract

“…Targeting proteins expressed on the gut surface has been a particularly successful approach for vaccine development in blood-feeding nematodes (Knox et al, 2003) and ectoparasites such as ticks (Willadsen et al, 1995). Munn (1977) first described contortin, using electron microscopy, as a helical polymeric extracellular structure present in large amounts in the intestine and the pharynx from the L4 and adult stage of the sheep parasite Haemonchus contortus.…”

Section: Introductionmentioning

confidence: 99%

“…However, it was shown subsequently that CEPs contained a 110 kDa major antigenic contaminant as judged by Western blotting despite only faint staining being evident in protein gels (Smith and Munn, 1990). This protein was purified using lectin-affinity chromatography and was subsequently defined as H11, the most effective immunogen isolated from a parasitic nematode to date (Knox et al, 2003). Subsequent effort focused on H11 and other gut proteins in Haemonchus and the exact nature and function of contortin was not investigated further.…”

Section: Introductionmentioning

confidence: 99%

The intestinal contortin structure in Haemonchus contortus: An immobilised anticoagulant?

Geldhof

Knox

2008

International Journal for Parasitology

View full text Add to dashboard Cite

Contortin was the first intestinal antigen of the sheep parasite Haemonchus contortus which induced significant levels of protection when used to vaccinate lambs. This antigen is present in the intestine of L4 and adult worms as a helical polymeric structure attached to the luminal surface of the intestinal cells. However, the nature of the protein itself and its function have never been reported. In the present study, contortin was isolated and analysed by peptide mass fingerprint and LC/MS-MS. These analyses indicated that contortin comprises two major proteins, Hc-PCP1 and Hc-PCP2, with homology to prolyl-carboxypeptidases. The two proteins show 64% amino acid sequence identity to each other and both are comprised of two prolyl-carboxypeptidase S28 type domains organised in a tandem repeat. The transcripts of both genes are present from the L4 stage onwards, coinciding with the onset of blood-feeding. Addition of contortin to a fibrinogen solution significantly inhibited blood coagulation in a dose-dependent manner. Mass-spectrometry indicated that the contortin-enriched fraction degraded the C-terminal end of the fibrinogen alpha-chain, which was shown previously to be essential for clot formation. The process happens within seconds after addition and can be inhibited by the dipeptidyl-peptidase IV inhibitors Diprotin A and Bt-PEG-Glu-Pro P (OPh) 2 . These data suggest that the prolyl-carboxypeptidases are intestinal anticoagulants used by H. contortus to interfere with blood coagulation. Ó

show abstract

“…Knox). [8]. These intestinal antigens induce high levels of protection in sheep against a H. contortus challenge infection, reducing faecal egg counts by 77-90% and worm burdens by 47-78%.…”

mentioning

confidence: 98%

“…The results indicated that the physical binding of antibody induced a stress response with a significant reduction in growth and fecundity of the adult worms. At the moment, the best working native vaccines against H. contortus are all based on gut expressed proteins [8] and, more importantly, antibody is thought to mediate this protective immunity by blocking or interfering with the digestion within the worm. One possibility is that this "physical" effect acts synergistically with specific enzyme inhibition to impair worm digestion and that RNAi targeting the C. elegans homologues does not induce a phenotype because the physical effect is absent.…”

mentioning

confidence: 99%

Assessment of Caenorhabditis elegans as a model in Haemonchus contortus vaccine research

Geldhof

Clark

Molloy

et al. 2007

Molecular and Biochemical Parasitology

View full text Add to dashboard Cite

The nature and prospects for gut membrane proteins as vaccine candidates for Haemonchus contortus and other ruminant trichostrongyloids

Cited by 132 publications

References 50 publications

Haemonchus contortus(Nematoda: Trichostrongylidae) infection in lambs elicits an unequivocal Th2 immune response

Haemonchus contortus(Nematoda: Trichostrongylidae) infection in lambs elicits an unequivocal Th2 immune response

The intestinal contortin structure in Haemonchus contortus: An immobilised anticoagulant?

Assessment of Caenorhabditis elegans as a model in Haemonchus contortus vaccine research

Contact Info

Product

Resources

About