Schistosoma mansoni egg granuloma size reduction in challenged baboons after vaccination with irradiated cryopreserved schistosomula.

Damian, Raymond T.; Roberts, MA; Powell, Malcolm R.; Clark, Julie D.; Lewis, Fred A.; Stirewált, M. A.

doi:10.1073/pnas.81.11.3552

Cited by 23 publications

(13 citation statements)

References 25 publications

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“…Schistosome eggs and their secreted products provide a continuous antigenic stimulus for the immune response. If these antigens are not sequestered or neutralized effectively, they can damage the affected tissues, with hepatocytes being particularly sensitive to toxins secreted by the eggs 3 . Indeed, T‐cell‐deprived, nude, severe combined immunodeficiency disease or egg‐tolerized mice all die earlier than comparably infected immunologically intact mice because they are unable to mount a protective granulomatous response.…”

Section: ‘The Good and The Bad’ Features Of Granulomasmentioning

confidence: 99%

“…If these antigens are not sequestered or neutralized effectively, they can damage the affected tissues, with hepatocytes being particularly sensitive to toxins secreted by the eggs. 3 Indeed, T-cell-deprived, nude, severe combined immunodeficiency disease or egg-tolerized mice all die earlier than comparably infected immunologically intact mice because they are unable to mount a protective granulomatous response. Widespread hepatic damage induced by toxic egg products contributes to the decreased survival of infected immunocompromised mice.…”

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Immunopathology of schistosomiasis

et al. 2006

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Waterborne parasitic diseases plague tropical regions of the world with the development of water resources often increasing transmission. Skin-penetrating cercariae (infectious stages of schistosome parasites) mature within their mammalian host, form sexual pairs and produce several hundred eggs per day. Many eggs are swept within the circulation and in the case of Schistosoma mansoni and S. japonicum, become lodged within hepatic sinusoids, invoking a fibrotic granulomatous response. Animal studies have identified a moderate type 1 helper (Th1) response to parasite antigens; however, a robust Th2 response to egg-derived antigens dominates and propagates fibrogenesis within the liver. Elegant T helper cell polarization studies have highlighted that critical control of Th1, Th2 and interleukin (IL)-17-secreting lymphocytes is necessary to prevent severe liver pathology. Alternatively activated macrophages develop in the Th2 milieu and upregulate Fizz1, Ym-1 and Arg-1. The possible contribution of macrophages to fibrogenesis and their role in immune regulation are discussed. Within the liver, natural (CD4 + CD25 + Forkhead box protein 3 (Foxp3) + ) and inducible (CD4 + Foxp3 -) Treg's are recruited, providing an essential regulatory arm to stabilize the immune response and limit immunopathology. This review ties together current thinking of how the granulomatous response develops, causing much of the associated immunopathology, with extensive discussions on how regulatory cells and cytokine decoy receptors serve to limit the extent of immune-mediated pathology during schistosomiasis.

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Section: ‘The Good and The Bad’ Features Of Granulomasmentioning

confidence: 99%

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confidence: 99%

Immunopathology of schistosomiasis

et al. 2006

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“…Most previous attempts at protection using irradiated larvae (Taylor, M.G. et al 1976, Damian et al 1984, James, E. et al 1986) have been disappointing. However one trial reported a decrease in both worm burden and faecal egg counts after immunization with gammaattenuated Schistosoma mansonicercariae (Stek et al 198 1).…”

Section: Introductionmentioning

confidence: 99%

Immunization of mice and baboons with the recombinant Sm28GST affects both worm viability and fecundity after experimental infection with Schistosoma mansoni

Boulanger

Reid

Sturrock

et al. 1991

Parasite Immunology

160

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A member of the glutathione S-transferase family, Sm28GST has previously demonstrated a good ability to protect rodents against experimental infection with Schistosoma mansoni. In order to evaluate its efficacy in a model closer to man, two different protocols of immunization with recombinant Sm28GST were tested on baboons in a large-scale trial. Three injections in the presence of aluminium hydroxide as adjuvant resulted in a significant 38% reduction in the adult worm burden together with a trend for a lower percentage of inflammatory tissue in the liver. Individual levels of protection, ranging from 0 to 80%, underlined the heterogeneity of the immune response to this purified molecule in outbred primates. On the other hand, two injections of Sm28GST in the presence of aluminium hydroxide and Bordetella pertussis reduced female schistosome fecundity by 33%, with a more pronounced effect (66%) on faecal egg output; there was also a trend, in this protocol, for decrease of the mean granuloma surface in the liver. Individual anti-Sm28GST IgG antibodies were apparently unrelated to levels of immunity, but there was partial evidence that cytophilic IgE might play a role in the immune mechanisms affecting worm viability, but not fecundity. In the mouse model, Sm28GST vaccination resulted in a lower hatching ability of tissue eggs recovered from immunized mice whereas passive transfer of specific anti-Sm28GST T-lymphocytes, one day before infection, significantly reduced the number of eggs in the liver of mice. We propose that different protocols of immunization with a recombinant molecule can impede Schistosoma mansoni worm viability and fecundity, but can also affect miracidium physiology, with important consequences for disease transmission and granuloma-derived pathology.

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“…Eggs trapped in the hepatic microvasculature induce the formation of granulomas. However, with time, infected individuals can modulate the granulomas and become relatively immune to reinfection by the process of concomitant immunity (Damian et al 1974(Damian et al , 1984. To be voided, Schistosoma mansoni eggs must penetrate the walls of the intestines.…”

Section: Discussionmentioning

confidence: 99%

Acute schistosomiasis mansoni in the baboon Papio anubis gives rise to goblet-cell hyperplasia and villus atrophy that are modulated by an irradiated cercarial vaccine

Farah

Nyindo

1997

Parasitology Research

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A histopathology study of the intestines of four Kenyan baboons (Papio anubis) infected by 800 cercariae of Schistosoma mansoni and euthanized at 10 weeks postinfection was done. The pathology was compared with that of four baboons first vaccinated with 10,000 irradiated cercariae and then challenged 8-10 weeks later with the same number of cercariae. Two baboons that were neither vaccinated nor challenged were used as controls. On postmortem examination, multifocal to coalescing granulomatous inflammatory responses to the eggs in the submucosa of the terminal ileum and colon were seen in all baboons exposed to the parasite. The mean numbers of goblet cells detected per villus at 20 cm from the pylorus were 12.8 +/- 2.6, 30.4 +/- 6.6, and 20.2 +/- 3.7 in the two uninfected baboons, the infected unvaccinated baboons, and the vaccinated and challenged baboons, respectively. Mild to total villus atrophy was present in all eight baboons exposed to the parasite. These lesions, which were less marked in infected but vaccinated baboons, may contribute to the clinical signs seen in acute simian schistosomiasis mansoni.

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Schistosoma mansoni egg granuloma size reduction in challenged baboons after vaccination with irradiated cryopreserved schistosomula.

Abstract: Young male baboons born in captivity were immunized with ad attenuated, cryopreserved schistosomular vaccine derived from V-irradiated (50

Cited by 23 publications

References 25 publications

Immunopathology of schistosomiasis

Immunopathology of schistosomiasis

Immunization of mice and baboons with the recombinant Sm28GST affects both worm viability and fecundity after experimental infection with Schistosoma mansoni

Acute schistosomiasis mansoni in the baboon Papio anubis gives rise to goblet-cell hyperplasia and villus atrophy that are modulated by an irradiated cercarial vaccine

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