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Elimination of Schistosoma mansoni Adult Worms by Rhesus Macaques: Basis for a Therapeutic Vaccine?

Wilson RA, Langermans JA, van Dam GJ, Vervenne RA, Hall SL, Borges WC, Dillon GP, Thomas AW, Coulson PS - PLoS Negl Trop Dis (2008)

Bottom Line: Using immunoproteomics, gut digestive enzymes, tegument surface hydrolases and antioxidant enzymes were identified as targets of IgG in the high responder animals.It appears that worms starve to death after cessation of blood feeding, as a result of antibody-mediated processes.We suggest that proteins in the three categories above, formulated to trigger the appropriate mechanisms operating in rhesus macaques, would have both prophylactic and therapeutic potential as a human vaccine.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, University of York, York, United Kingdom. raw3@york.ac.uk

ABSTRACT

Background: Among animal models of schistosomiasis, the rhesus macaque is unique in that an infection establishes but egg excretion rapidly diminishes, potentially due to loss of adult worms from the portal system via shunts or death by immune attack.

Principal findings: To investigate this, six rhesus macaques were exposed to Schistosoma mansoni cercariae and the infection monitored until portal perfusion at 18 weeks. Despite a wide variation in worm numbers recovered, fecal egg output and circulating antigen levels indicated that a substantial population had established in all animals. Half the macaques had portal hypertension but only one had portacaval shunts, ruling out translocation to the lungs as the reason for loss of adult burden. Many worms had a shrunken and pallid appearance, with degenerative changes in intestines and reproductive organs. Tegument, gut epithelia and muscles appeared cytologically intact but the parenchyma was virtually devoid of content. An early and intense IgG production correlated with low worm burden at perfusion, and blood-feeding worms cultured in the presence of serum from these animals had stunted growth. Using immunoproteomics, gut digestive enzymes, tegument surface hydrolases and antioxidant enzymes were identified as targets of IgG in the high responder animals.

Significance: It appears that worms starve to death after cessation of blood feeding, as a result of antibody-mediated processes. We suggest that proteins in the three categories above, formulated to trigger the appropriate mechanisms operating in rhesus macaques, would have both prophylactic and therapeutic potential as a human vaccine.

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Related in: MedlinePlus

Blood feeding and fecal egg output decline from soon after patency.Worm gut function as an indicator of physiological status, determined by the concentration of CAA in the bloodstream of rhesus macaques (•). Fecundity of the worm population, revealed by fecal egg output (□). Values are mean + or − SE. n = 6 animals.
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pntd-0000290-g001: Blood feeding and fecal egg output decline from soon after patency.Worm gut function as an indicator of physiological status, determined by the concentration of CAA in the bloodstream of rhesus macaques (•). Fecundity of the worm population, revealed by fecal egg output (□). Values are mean + or − SE. n = 6 animals.

Mentions: CAA and fecal egg output were monitored, as indirect indicators of the status of the schistosome infection (Figure 1). The production of CAA rose steadily as worms began blood feeding and reached maturity, with mean values peaking at week 8 before declining to a plateau from week 12 onwards. Eggs were first detected in the feces at week 7, with mean numbers peaking at week 9 before declining towards the baseline; in two cases egg excretion reached zero by the end of the study. Although data from individual animals showed a wide variation for the two indirect indicators (Table 1), their peak values revealed that appreciable numbers of parasites established in all rhesus macaques. However, there was a large discrepancy in the number of worms recovered at perfusion (range 12–708; Table 1), signifying that many had been lost from the portal system in some animals.


Elimination of Schistosoma mansoni Adult Worms by Rhesus Macaques: Basis for a Therapeutic Vaccine?

Wilson RA, Langermans JA, van Dam GJ, Vervenne RA, Hall SL, Borges WC, Dillon GP, Thomas AW, Coulson PS - PLoS Negl Trop Dis (2008)

Blood feeding and fecal egg output decline from soon after patency.Worm gut function as an indicator of physiological status, determined by the concentration of CAA in the bloodstream of rhesus macaques (•). Fecundity of the worm population, revealed by fecal egg output (□). Values are mean + or − SE. n = 6 animals.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2553480&req=5

pntd-0000290-g001: Blood feeding and fecal egg output decline from soon after patency.Worm gut function as an indicator of physiological status, determined by the concentration of CAA in the bloodstream of rhesus macaques (•). Fecundity of the worm population, revealed by fecal egg output (□). Values are mean + or − SE. n = 6 animals.
Mentions: CAA and fecal egg output were monitored, as indirect indicators of the status of the schistosome infection (Figure 1). The production of CAA rose steadily as worms began blood feeding and reached maturity, with mean values peaking at week 8 before declining to a plateau from week 12 onwards. Eggs were first detected in the feces at week 7, with mean numbers peaking at week 9 before declining towards the baseline; in two cases egg excretion reached zero by the end of the study. Although data from individual animals showed a wide variation for the two indirect indicators (Table 1), their peak values revealed that appreciable numbers of parasites established in all rhesus macaques. However, there was a large discrepancy in the number of worms recovered at perfusion (range 12–708; Table 1), signifying that many had been lost from the portal system in some animals.

Bottom Line: Using immunoproteomics, gut digestive enzymes, tegument surface hydrolases and antioxidant enzymes were identified as targets of IgG in the high responder animals.It appears that worms starve to death after cessation of blood feeding, as a result of antibody-mediated processes.We suggest that proteins in the three categories above, formulated to trigger the appropriate mechanisms operating in rhesus macaques, would have both prophylactic and therapeutic potential as a human vaccine.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, University of York, York, United Kingdom. raw3@york.ac.uk

ABSTRACT

Background: Among animal models of schistosomiasis, the rhesus macaque is unique in that an infection establishes but egg excretion rapidly diminishes, potentially due to loss of adult worms from the portal system via shunts or death by immune attack.

Principal findings: To investigate this, six rhesus macaques were exposed to Schistosoma mansoni cercariae and the infection monitored until portal perfusion at 18 weeks. Despite a wide variation in worm numbers recovered, fecal egg output and circulating antigen levels indicated that a substantial population had established in all animals. Half the macaques had portal hypertension but only one had portacaval shunts, ruling out translocation to the lungs as the reason for loss of adult burden. Many worms had a shrunken and pallid appearance, with degenerative changes in intestines and reproductive organs. Tegument, gut epithelia and muscles appeared cytologically intact but the parenchyma was virtually devoid of content. An early and intense IgG production correlated with low worm burden at perfusion, and blood-feeding worms cultured in the presence of serum from these animals had stunted growth. Using immunoproteomics, gut digestive enzymes, tegument surface hydrolases and antioxidant enzymes were identified as targets of IgG in the high responder animals.

Significance: It appears that worms starve to death after cessation of blood feeding, as a result of antibody-mediated processes. We suggest that proteins in the three categories above, formulated to trigger the appropriate mechanisms operating in rhesus macaques, would have both prophylactic and therapeutic potential as a human vaccine.

Show MeSH
Related in: MedlinePlus