Aspartyl proteases from the intestinal brush border of <i>Haemonchus contortus</i> as protective antigens for sheep

Smith, W.D.; Skuce, Philip; Newlands, G. F. J.; Smith, S. K.; Pettit, D.

doi:10.1111/j.0141-9838.2004.00667.x

Cited by 39 publications

(38 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A second aspartyl protease, designated HcPEP2, showed 50% sequence identity with HcPEP1. 33 $ IUDFWLRQ RI +JDO*3 SUHSDUHG E\ JHO ¿OWUDWLRQ LQ 0 XUHD FRQWDLQLQJ ERWK +F3(3 DQG UHGXFHG IDHFDO HJJ RXWSXW E\ DQG ¿QDO ZRUP EXUGHQV E\ 36% compared to controls. The HcPEP1 and 2 fraction did not protect if electro-eluted from SDS-dissociated H-gal-GP, nor did bacterially-expressed recombinant HcPEP1, suggesting that conformational epitopes are important for inducing immunity.…”

Section: H11mentioning

confidence: 99%

Proteases in Blood-Feeding Nematodes and Their Potential as Vaccine Candidates

Knox

2011

Advances in Experimental Medicine and Biology

View full text Add to dashboard Cite

Parasitic nematodes express and secrete a variety of proteases which they use for many purposes including the penetration of host tissues, digestion of host protein for nutrients, evasion of host immune responses and for internal processes such as tissue catabolism and apoptosis. For these broad reasons they have been examined as possible parasite control targets. Blood-feeding nematodes such as the barber-pole worm Haemonchus contortus that infect sheep and goats and the hookworms, Ancylostoma spp. and Necator americanus, affecting man, use an array of endo- and exopeptidases to digest the blood meal. Haemoglobin digestion occurs by an ordered and partly conserved proteolytic cascade. These proteases are accessible to host immune responses which can block enzyme function and lead to parasite expulsion and/or death. Thus they are receiving attention as components of vaccines against several parasitic nematodes of social and economic importance.

show abstract

Section: H11mentioning

confidence: 99%

Proteases in Blood-Feeding Nematodes and Their Potential as Vaccine Candidates

Knox

2011

Advances in Experimental Medicine and Biology

View full text Add to dashboard Cite

show abstract

“…Haemonchus galactose-containing glycoprotein is a protein complex from the intestine of the sheep barber's pole worm, H. contortus. Vaccination of sheep with H-gal-GP confers high levels of protection against parasite challenge; the complex is predominantly made up of aspartic, cysteine, and metalloproteases (57), and recent evidence suggests that the purified enzymes from Haemonchus galactose-containing glycoprotein are responsible for the vaccine efficacy (44,58,59). We recently described the efficacy of Ac-CP-2 as an anti-hookworm vaccine in dogs experimentally challenged with A. caninum (21).…”

Section: Ac-apr-1 Ac-cp-2 and Ac-mep-1 Degrade Hb In A Semiorderedmentioning

confidence: 99%

A Multi-enzyme Cascade of Hemoglobin Proteolysis in the Intestine of Blood-feeding Hookworms

Williamson¹,

Lecchi

Turk

et al. 2004

Journal of Biological Chemistry

157

115

View full text Add to dashboard Cite

Blood-feeding pathogens digest hemoglobin (Hb) as a source of nutrition, but little is known about this process in multicellular parasites. The intestinal brush border membrane of the canine hookworm, Ancylostoma caninum, contains aspartic proteases (APR-1), cysteine proteases (CP-2), and metalloproteases (MEP-1), the first of which is known to digest Hb. We now show that Hb is degraded by a multi-enzyme, synergistic cascade of proteolysis. Recombinant APR-1 and CP-2, but not MEP-1, digested native Hb and denatured globin. MEP-1, however, did cleave globin fragments that had undergone prior digestion by APR-1 and CP-2. Proteolytic cleavage sites within the Hb ␣ and ␤ chains were determined for the three enzymes, identifying a total of 131 cleavage sites. By scanning synthetic combinatorial peptide libraries with each enzyme, we compared the preferred residues cleaved in the libraries with the known cleavage sites within Hb. The semi-ordered pathway of Hb digestion described here is surprisingly similar to that used by Plasmodium to digest Hb and provides a potential mechanism by which these hemoglobinases are efficacious vaccines in animal models of hookworm infection.

show abstract

“…Greatest efficacy has been achieved with vaccines that use irradiated larvae (5), but the logistical problems involved in their production and administration (6) have led to a search for native antigens or recombinant ones (7). The latter are easier to produce and distribute, and many of them are proteases, cysteine proteases, metalloproteases, aspartyl proteases (PEPs), all proteins from the helminth intestine, and some with unknown biological functions (8)(9)(10)(11). Due to the homology in their sequences, some of these antigens have proved to be effective against different nematode species (3,12,13).…”

mentioning

confidence: 99%

Intranasal Immunization of Lambs with Serine/Threonine Phosphatase 2A against Gastrointestinal Nematodes

Fawzi

Cruz‐Bustos

Samblas

et al. 2013

Clin Vaccine Immunol

View full text Add to dashboard Cite

b Seven 3-month-old, female, helminth-free lambs were immunized intranasally with three doses (1 mg total) of a recombinant part of the catalytic region of the serine/threonine phosphatase 2A (PP2Ar) (group 1 [G1]). In addition, four lambs were used as an adjuvant control group (G2), four as unimmunized, infected controls (G3), and four as unimmunized, uninfected controls (G4). Fifteen days after the last immunization, lambs from G1, G2, and G3 were challenged with 10,000 larval stage 3 (L3) organisms in a plurispecific nematode infection composed of ca. 40% Trichostrongylus colubriformis, 40% Haemonchus contortus, and 20% Teladorsagia circumcincta. All the lambs were clinically monitored throughout the experiment. Parasitological (fecal egg output and immunological response), biopathological (packed-cell volume and leukocyte and eosinophil counts), and zootechnical (live-weight gain) analyses were conducted. On day 105 of the experiment, all the animals were slaughtered and the adult worm population in their abomasa examined. Intranasal administration of PP2Ar with bacterial walls as an adjuvant elicited a strong immune response in the immunized lambs, as evidenced by their humoral immune response. Immunized animals and animals receiving the adjuvant shed significantly (P < 0.001) fewer numbers of parasites' eggs in their feces. The immunization significantly reduced the helminth burden in the abomasa by the end of the experiment (>68%), protection being provided against both Haemonchus and Teladorsagia. Live-weight gain in the immunized lambs was similar to that in the uninfected controls versus the infected or adjuvanted animal groups. Our results suggest that heterologous immunization of ruminants by intranasal administration may be efficacious in the struggle to control gastrointestinal helminths in these livestock.

show abstract

Aspartyl proteases from the intestinal brush border of Haemonchus contortus as protective antigens for sheep

Cited by 39 publications

References 17 publications

Proteases in Blood-Feeding Nematodes and Their Potential as Vaccine Candidates

Proteases in Blood-Feeding Nematodes and Their Potential as Vaccine Candidates

A Multi-enzyme Cascade of Hemoglobin Proteolysis in the Intestine of Blood-feeding Hookworms

Intranasal Immunization of Lambs with Serine/Threonine Phosphatase 2A against Gastrointestinal Nematodes

Contact Info

Product

Resources

About