Nematode gut peptidases, proteins and vaccination.

Knox, David P.; Skuce, Philip; Newlands, G. F. J.; Redmond, D. L.; Kennedy, Malcolm W.; Harnett, William

doi:10.1079/9780851994239.0247

Cited by 6 publications

(4 citation statements)

References 42 publications

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“…Immunization of sheep with the intestinal brush border complex, H-gal-GP, confers high levels of protection (both antiparasite and antifecundity) against H. contortus and at least three different protease activities, including aspartic proteases, have been detected in this extract [16,41]. Immunization of sheep with aspartic protease-enriched fractions of H. contortus membranes resulted in 36% reduction in adult worms and 48% reduction in fecal egg output [17].…”

Section: Discussionmentioning

confidence: 99%

Vaccination with Recombinant Aspartic Hemoglobinase Reduces Parasite Load and Blood Loss after Hookworm Infection in Dogs

et al. 2005

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BackgroundHookworms infect 730 million people in developing countries where they are a leading cause of intestinal blood loss and iron-deficiency anemia. At the site of attachment to the host, adult hookworms ingest blood and lyse the erythrocytes to release hemoglobin. The parasites subsequently digest hemoglobin in their intestines using a cascade of proteolysis that begins with the Ancylostoma caninum aspartic protease 1, APR-1.Methods and FindingsWe show that vaccination of dogs with recombinant Ac-APR-1 induced antibody and cellular responses and resulted in significantly reduced hookworm burdens (p = 0.056) and fecal egg counts (p = 0.018) in vaccinated dogs compared to control dogs after challenge with infective larvae of A. caninum. Most importantly, vaccinated dogs were protected against blood loss (p = 0.049) and most did not develop anemia, the major pathologic sequela of hookworm disease. IgG from vaccinated animals decreased the catalytic activity of the recombinant enzyme in vitro and the antibody bound in situ to the intestines of worms recovered from vaccinated dogs, implying that the vaccine interferes with the parasite's ability to digest blood.ConclusionTo the best of our knowledge, this is the first report of a recombinant vaccine from a hematophagous parasite that significantly reduces both parasite load and blood loss, and it supports the development of APR-1 as a human hookworm vaccine.

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Section: Discussionmentioning

confidence: 99%

Vaccination with Recombinant Aspartic Hemoglobinase Reduces Parasite Load and Blood Loss after Hookworm Infection in Dogs

et al. 2005

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“…The enzymatic systems linked to haematophagy are likely to be conserved (Williamson et al 2003) and antibodies targeting the digestive enzymes of haemoglobin might lead to a reduction of filarial worm burden and pathology. Studies on haematophagous intestinal nematodes of veterinarian importance are providing a number of vaccine candidates (Knox et al 2001 ;Smith et al 2003), and some of which implicated in haematophagy might point to homologues in human filariasis as novel targets of vaccination.…”

Section: Discussionmentioning

confidence: 99%

Blood-feeding in the young adult filarial wormsLitomosoides sigmodontis

Attout

Babayan

Hoerauf³

et al. 2004

Parasitology

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In this study with the filarial model Litomosoides sigmodontis, we demonstrate that the worms ingest host red blood cells at a precise moment of their life-cycle, immediately after the fourth moult. The red blood cells (RBC) were identified microscopically in live worms immobilized in PBS at 4 xC, and their density assessed. Two hosts were used : Mongolian gerbils, where microfilaraemia is high, and susceptible BALB/c mice with lower microfilaraemia. Gerbils were studied at 12 time-points, between day 9 post-inoculation (the worms were young 4th stage larvae) and day 330 p.i. (worms were old adults). Only the very young adult filarial worms had red blood cells in their gut. Haematophagy was observed between days 25 and 56 p.i. and peaked between day 28 and day 30 p.i. in female worms. In males, haematophagy was less frequent and intense. Similar kinetics of haematophagy were found in BALB/c mice, but frequency and intensity tended to be lower. Haematophagy seems useful to optimize adult maturation. These observations suggest that haematophagy is an important step in the life-cycle of L. sigmodontis. This hitherto undescribed phenomenon might be characteristic of other filarial species including human parasites.

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“…The second class of hookworm antigens that are offering promise as vaccines are the haemoglobindegrading proteases of the hookworm gut, or haemoglobinases. Gut-derived molecules have been effectively employed as vaccine antigens against ectoparasites of domestic animals [43] and protection of sheep against the barberÕs pole worm, Haemonchus contortus [44]. Much effort has been directed towards the development of a vaccine against Haemonchus, and the most promising candidates are parasite extracts enriched for gut membrane proteases that are thought to be responsible for haemoglobin digestion.…”

Section: Vaccinesmentioning

confidence: 99%

Immunobiology of hookworm infection

Loukas

Constant

Bethony

2005

FEMS Immunology &Amp; Medical Microbiology

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Hookworms infect almost one billion people and are a major cause of iron-deficiency anaemia in developing countries of the tropics. Despite their prevalence and the morbidity they cause, little is known about the immune response to this complex eukaryotic parasite. Recent publications have shed light on the human cellular immune responses to hookworms, as well as mechanisms that hookworms utilize to skew the immune response in its favour. Unlike most other human helminth infections, neither age- nor exposure-related immunity develops in the majority of infected people. A vaccine is therefore a highly desirable goal. To this end, gene sequencing efforts have resulted in the deposition of more than 10,000 hookworm cDNA sequences in the public domain, providing a molecular snapshot of this intriguing parasite and providing novel tools for the development of new control strategies. Significant progress has been made in the development of anti-hookworm recombinant vaccines, and clinical trials are expected to begin in the near future.

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Nematode gut peptidases, proteins and vaccination.

Cited by 6 publications

References 42 publications

Vaccination with Recombinant Aspartic Hemoglobinase Reduces Parasite Load and Blood Loss after Hookworm Infection in Dogs

Vaccination with Recombinant Aspartic Hemoglobinase Reduces Parasite Load and Blood Loss after Hookworm Infection in Dogs

Blood-feeding in the young adult filarial wormsLitomosoides sigmodontis

Immunobiology of hookworm infection

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