Evidence that Both Normal and Immune Elimination of Schistosoma Mansoni take Place at the Lung Stage of Migration Prior to Parasite Death

Dean, David A.; Mangold, Beverly L.

doi:10.4269/ajtmh.1992.47.238

Cited by 52 publications

(36 citation statements)

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“…By recovery of parasites following mincing and incubation of tissue (Minard et al 1978 b ;Stek et al 1981 a) by quantitative histology (Mastin et al 1983 ;Von Lichtenberg et al 1985) and most accurately by autoradiographic tracking in compressed organs Wilson et al 1986 ;Dean and Mangold, 1992) it was shown that migration of percutaneously applied challenge larvae to the lungs is delayed in vaccinated compared with naïve mice but otherwise comparable. Subsequently, a greater proportion of schistosomula are retained in the lungs of vaccinated mice and these gradually disappear between 2-5+ weeks post-infection Dean and Mangold, 1992). LS introduced by i.v.…”

Section: A)mentioning

confidence: 99%

Radiation-attenuated schistosome vaccination – a brief historical perspective

Bickle

2009

Parasitology

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The high level of protection which can be induced by vaccination of a range of hosts, from rodents to primates, with live radiation-attenuated schistosome larvae offers great promise for development of a human schistosome vaccine. Studies of the irradiated vaccine models benefitted from significant funding during the 1970-90s and much was learned concerning the inducers, targets and mechanisms of immunity. Less progress was made in definition of the protective antigens involved. The application of new techniques for identifying membrane and secreted antigens has recently provided new vaccine candidates and a new impetus for schistosome vaccine development. This article is intended as an overview of some of the main lessons learned from the studies of the irradiated vaccines as a backdrop to renewed interest in schistosome vaccine development.

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Section: A)mentioning

confidence: 99%

Radiation-attenuated schistosome vaccination – a brief historical perspective

Bickle

2009

Parasitology

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“…However, the IgE/IgG4 ratio was indeed correlated inversely with infection levels, supporting the idea that the presence of IgG4 might block a protective role of IgE in the most-infected subjects. In mice, IFN-␥-activated macrophages are important in parasite destruction in the lungs (17,43,(62)(63)(64). The present study supports the role of IFN-␥ production in the protective response in human beings by showing higher levels of this cytokine in partially or completely resistant subjects.…”

Section: Vol 68 2000 Immune Response To S Mansoni Vaccine Candidatmentioning

confidence: 99%

Human Immune Responses toSchistosoma mansoniVaccine Candidate Antigens

et al. 2000

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To determine the naturally occurring immunological responses to the Schistosoma mansoni antigens paramyosin, IrV-5, Sm-23 (MAP-3), and triose phosphate isomerase (MAP-4), a total of 119 subjects from an area of endemicity for schistosomiasis, including "resistant" subjects (n ‫؍‬ 17) were evaluated. Specific immunoglobulin G1 (IgG1), IgG2, IgG3, IgG4, and IgA levels for each of the antigens and the cytokine profile in culture supernatants from antigen-stimulated peripheral blood mononuclear cells (PBMC) were determined. Although all the subjects had a high degree of contaminated water exposure, their infection levels were variable (0 to 1,128 eggs/g of stool). There were direct correlations between infection levels and levels of SWAP-and paramyosin-specific IgG1 and IgG4 (P < 0.05). However, an inverse correlation between infection levels and specific IgG2 to IrV-5 (P < 0.01) was observed. The evaluation of the cytokine profile (interleukin 5 [IL-5], IL-10, gamma interferon [IFN-␥], and tumor necrosis factor alpha) in response to these antigens showed inverse correlations between the degree of infection and IFN-␥ levels in PBMC supernatants stimulated with paramyosin (P < 0.05) and IrV-5 (P < 0.01). Additionally, inverse correlations between the degree of infection and IL-5 levels in MAP-3-and MAP-4-stimulated PBMC supernatants (P < 0.01) were found. Logistic regression analysis was performed to adjust the results of cytokine profile by age. IL-5 production in MAP-3-stimulated PBMC supernatants was associated with lower infection levels (odds ratio ‫؍‬ 11.2 [95% confidence interval, 2.7 to 45.8]).Schistosomiasis is a chronic parasitic infection that affects 200 million people in Africa, South America, and Asia (35). Although treatment of infected people with schistosomicidal drugs has in part controlled the morbidity of the disease, transmission is largely unaltered (3,5,24). The possibility of a schistosomiasis vaccine as an additional measure to control the disease arose from the fact that the parasite does not multiply in human beings and that reduction of infection levels by schistosomicidal drugs reduces the prevalence of severe forms of the disease. Moreover, in experimental models, partial immunity can be induced by vaccination with irradiated cercariae or specific antigens (2,11,14,26,36,37,58,59). Immunological studies of subjects from areas of endemicity have demonstrated a naturally occurring resistance to reinfection (4, 19, 22-25, 27, 28). Both high levels of specific immunoglobulin E (IgE) in sera and gamma interferon (IFN-␥) in antigen-stimulated peripheral blood mononuclear cell (PBMC) cultures were associated with resistance to reinfection (1,22,24,25,27,28,56,57). These data suggest the participation of immunological mechanisms in human resistance to Schistosoma mansoni infection, with mixed cellular and humoral responses.Several S. mansoni antigens have been identified and tested in experimental models, with the induction of variable levels of protection against infection (11,32,49,59,61,(68)...

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“…8 and 9), concomitantly inducing a markedly high level of IgG2a and IgG2b compared with adjuvant alone (Table 2). Th1-type response seems to be key to induce resistance against schistosomiasis in mice as described in several studies, demonstrating that the major mechanism of protective immunity was cell-mediated immunity involving interferon-γ-activated effector cells and schistosomula elimination at lung stage by macrophages or endothelial cells activated via a highly apparently increase of Th1 cytokines (Dean and Mangold 1992;Wynn et al 1994). Therefore, a low IgG1:(IgG2a+IgG2b) ratio, indicative of Th1-type response, is associated with a high protection level using SjCa8 as a vaccine candidate and SjCa8 may present a feasible to rational strategy to minimize the pathogenesis resulting from schistosome infection.…”

Section: Discussionmentioning

confidence: 94%

Expression profile, localization of an 8-kDa calcium-binding protein from Schistosoma japonicum (SjCa8), and vaccine potential of recombinant SjCa8 (rSjCa8) against infections in mice

Yang

et al. 2008

Parasitol Res

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Researches on genes expressed in a cercarial stage-specific manner may help us understand the molecular events and functions during schistosome invasion of skin. A genomic clone encoding 8-kDa calcium-binding protein (SjCa8) specifically expressed in cercariae and skin-stage schistosomulum (transformed within 3 h) was obtained from cercariae. Recombinant protein was expressed in vector pET32a (+) and purified using a Ni-NTA purification system. The target protein SjCa8 was determined by matrix-assisted laser desorption/ionization time-of-flight (TOF)/TOF mass spectrometer after thrombin digestion and dialysis. Reverse transcriptase polymerase chain reaction and Western blot revealed SjCa8 can be detected in cercaria and skin-stage schistosomulum but not lung-stage schistosomulum, adult, or egg and was localized to head gland, penetration gland tubes, and penetration glands where Ca(2+) was abundant, and the cercarial tegument (but not tegument of tail) and body-tail junction. Furthermore, SjCa8 was interestingly detected in cercarial secretions. The characterization of SjCa8 indicated that it may undergo structural and physiological modifications, including repair of the surface membrane, changes in permeability that account for the loss of water tolerance, activities of calcium-depending enzymes, and immune signaling, etc. Furthermore, vaccination with rSjCa8 plus adjuvant induced protective effect with 50.39% worm reduction rate and significantly high hepatic and intestine egg reduction rates (54.16%, 50.63%, respectively), which is possibly mediated through an apparent induction of Th1-type immune response for strikingly high level of IgG2a and IgG2b developed in immunized C57BL/6 mice.

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Evidence that Both Normal and Immune Elimination of Schistosoma Mansoni take Place at the Lung Stage of Migration Prior to Parasite Death

Cited by 52 publications

References 0 publications

Radiation-attenuated schistosome vaccination – a brief historical perspective

Radiation-attenuated schistosome vaccination – a brief historical perspective

Human Immune Responses toSchistosoma mansoniVaccine Candidate Antigens

Expression profile, localization of an 8-kDa calcium-binding protein from Schistosoma japonicum (SjCa8), and vaccine potential of recombinant SjCa8 (rSjCa8) against infections in mice

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