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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

Humoral responses are implicated in declining worm fitness.Antibody responses during infection monitored by ELISA using SWAP as coating antigen. A) IgM and B) IgG. Values are mean ±SE, n = 6 animals. C) IgG levels at weeks 8 (□) and 18 (•) for individual animals plotted against the number of worms recovered at week 18.
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pntd-0000290-g004: Humoral responses are implicated in declining worm fitness.Antibody responses during infection monitored by ELISA using SWAP as coating antigen. A) IgM and B) IgG. Values are mean ±SE, n = 6 animals. C) IgG levels at weeks 8 (□) and 18 (•) for individual animals plotted against the number of worms recovered at week 18.

Mentions: We investigated whether the declining physiological status of worms was correlated with the humoral immune response. IgM, probed with SWAP, peaked at week 8 before gradually declining over the period of worm deterioration (Figure 4A) whereas IgG levels rose to a sustained plateau, with considerable variation between individual animals (Figure 4B). The values for IgG level at weeks 8 and 18, plotted against final worm burden, fell into 3 groups (Figure 4C). In the two animals with lowest worm recoveries, levels were already high at week 8 and remained so at week 18. Conversely, in the two with highest burdens, levels were low at week 8 with only small increments apparent by week 18. The animals with intermediate burdens had the largest increments in IgG levels between the two sampling times. Levels of total IgE showed only a small perturbation from normal (4–5 IU) around week 8 but had returned to background by week 12 (data not shown).


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)

Humoral responses are implicated in declining worm fitness.Antibody responses during infection monitored by ELISA using SWAP as coating antigen. A) IgM and B) IgG. Values are mean ±SE, n = 6 animals. C) IgG levels at weeks 8 (□) and 18 (•) for individual animals plotted against the number of worms recovered at week 18.
© Copyright Policy
Related In: Results  -  Collection

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

pntd-0000290-g004: Humoral responses are implicated in declining worm fitness.Antibody responses during infection monitored by ELISA using SWAP as coating antigen. A) IgM and B) IgG. Values are mean ±SE, n = 6 animals. C) IgG levels at weeks 8 (□) and 18 (•) for individual animals plotted against the number of worms recovered at week 18.
Mentions: We investigated whether the declining physiological status of worms was correlated with the humoral immune response. IgM, probed with SWAP, peaked at week 8 before gradually declining over the period of worm deterioration (Figure 4A) whereas IgG levels rose to a sustained plateau, with considerable variation between individual animals (Figure 4B). The values for IgG level at weeks 8 and 18, plotted against final worm burden, fell into 3 groups (Figure 4C). In the two animals with lowest worm recoveries, levels were already high at week 8 and remained so at week 18. Conversely, in the two with highest burdens, levels were low at week 8 with only small increments apparent by week 18. The animals with intermediate burdens had the largest increments in IgG levels between the two sampling times. Levels of total IgE showed only a small perturbation from normal (4–5 IU) around week 8 but had returned to background by week 12 (data not shown).

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