Schistosome vaccines

Taylor, David W.

doi:10.1007/bf01945416

Cited by 18 publications

(11 citation statements)

References 54 publications

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“…Subsequently, as the child ages, the balance may switch from a predominantly blocking to a predominantly protective type of response, and the child may then express his capacity to resist reinfection.' This hypothesis elaborated an earlier suggestion by Iskander et al (1981), and has since been refined as specific IgE, IgG1, IgG3 and possibly IgA have been shown to effect killing of schistosomulae, and both specific IgM and IgG4 (and possibly others) have been shown to exhibit blocking activity (see reviews by Taylor 1991, Hagan 1992, Butterworth et af. 1992.…”

Section: Introductionsupporting

confidence: 60%

“…This is clearly important for understanding epidemiological patterns of human schistosome infection, with possible relevance to other helminth infections. The analysis may also be relevant to predicting the potential impact of vaccines, as blocking responses may interfere with the development of vaccine-induced protection (Bergquist 1990, Taylor 1991).…”

Section: Introductionmentioning

confidence: 99%

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A theoretical framework for the immunoepidemiology of blocking antibodies to helminth infection

Woolhouse

1994

Parasite Immunology

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Epidemiological evidence is widely cited in support of the hypothesis that certain antibody responses to human helminth, especially schistosome, infection exhibit blocking activity. This evidence includes positive correlations between antibody levels and the rate of re-establishment of infection following chemotherapy, antibody levels which peak in younger and more susceptible age classes, lower ratios of blocking antibodies to others in older and less susceptible age classes. In this paper simple mathematical models are used to explore expected age-specific relationships between antibody levels, parasite burdens and re-establishment rates for different combinations of protective, neutral and blocking immune responses. In general, all the above cited patterns may be generated without invoking blocking activity, especially if the abilities to produce different antibody responses have different immunological memories, i.e. persist for different lengths of time in the absence of continued exposure to antigen. None of these patterns, including a positive correlation between antibody levels and rates of re-establishment following chemotherapy, offers unambiguous evidence for blocking activity. Blocking activity is also predicted to affect the shape of the age-intensity curve and the relationship between susceptibility to infection and age in ways which are not necessarily consistent with the epidemiological evidence. The importance of the blocking activity, which has been convincingly demonstrated in vitro, to population level immunoepidemiological patterns in the field therefore remains uncertain.

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Section: Introductionsupporting

confidence: 60%

Section: Introductionmentioning

confidence: 99%

A theoretical framework for the immunoepidemiology of blocking antibodies to helminth infection

Woolhouse

1994

Parasite Immunology

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“…Once drug treatment ceases, with time infection rates reach pretreatment levels (26). This, coupled with the risk of drug resistance, supports the need for the development of a vaccination program that would result in control of transmission and permanent reduction of morbidity (63). The ultimate goal of our research is the development of an efficacious vaccine against schistosomiasis that contains parasite-specific epitopes.…”

Section: Discussionmentioning

confidence: 81%

Cross-Reactivity ofSchistosoma mansoniCytosolic Superoxide Dismutase, a Protective Vaccine Candidate, with Host Superoxide Dismutase and Identification of Parasite-Specific B Epitopes

Carvalho-Queiroz¹,

Cook²,

Wang

et al. 2004

Infect Immun

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Schistosoma mansoni, an intravascular parasite, has evolved a number of immune evasion mechanisms to establish itself in the host, such as antioxidant enzymes. Our laboratory has demonstrated that the highest levels of certain antioxidant enzymes are found in adult worms, which are the least susceptible to immune killing. Vaccination of mice with naked DNA constructs containing the gene encoding Cu/Zn cytosolic superoxide dismutase (SmCT-SOD) showed significant levels of protection compared to a control group, and our data demonstrate that the adult worms are a target of the immune response that confers resistance in SmCT-SOD DNA-vaccinated mice. Because SmCT-SOD shows significant identity with the human homologue, we evaluated the reactivity of anti-SmCT-SOD antibodies derived from SmCT-SOD-immunized mice and rabbits and from S. mansoni-infected individuals to human superoxide dismutase (hSOD) and SmCT-SOD parasite-specific peptides to assess the potential for autoimmune responses from immunization with the recombinant molecule. In addition, we evaluated the ability of various SmCT-SOD adjuvant-delivered immunizations to induce cross-reactive antibodies. Both mouse and rabbit antibodies generated against SmCT-SOD recognized the denatured form of hSOD. The same antibodies did not recognize nondenatured hSOD. Sera from infected individuals with different clinical forms of schistosomiasis recognized SmCT-SOD but not hSOD. Antibodies from mice immunized with different SmCT-SOD-containing formulations of both DNA and protein were able to recognize SmCT-SOD-derived peptides but not soluble hSOD. All together, these findings serve as a basis for developing a subunit vaccine against schistosomiasis.Schistosomiasis remains an endemic problem in over 76 countries, although approaches to reduce transmission and morbidity as well as to improve sanitation, mollusciciding and mass chemotherapy, have been attempted (3, 13). Vaccine development to control schistosomiasis is a high priority, as it would offer the potential of cost-efficient, long-lasting prophylaxis (2, 65). Schistosoma mansoni, an intravascular parasite, lives in a hostile environment in close contact with host humoral and cellular cytotoxic factors. Larval parasite killing mechanisms include the release of oxidants by eosinophils, neutrophils, and macrophages potentiated by antibodies and/or cytokines (8,12,16,31,32). However, to establish itself in the host, the parasite has evolved a number of immune evasion mechanisms (17,39,51,60), such as antioxidant enzymes (7,11,30,37). These are essential enzymes involved in the prevention of reactive oxygen species-derived damage. Evidence for the involvement of schistosome antioxidant enzymes, such as cytosolic superoxide dismutase (SmCT-SOD) and glutathione peroxidase (SmGPX), in immune evasion has been presented elsewhere (39). SmCT-SOD and GPX localize to the host-parasite interface (worm tegument and gut epithelium of the adult but not the larval schistosome) (41) and show developmental regulation (29,41,42) wit...

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“…[1][2][3][4] Abbreviations used in this paper: BPV, Bordetella pertussis vaccine; CsA, cyclosporin A; c/m, cercariae per mouse; FCA, Freund's complete adjuvant; GSH, glutathione; GST, glutathione-S-transferase; IgE immunoglobulin E; i.n., intranasally; i.p., intraperitoneally; KLH, keyhole limpet haemocyanin; PBS, phosphate buffered saline pH 7 3; PZQ, praziquantel; s.c, subcutaneously; SPF, specific pathogen free. part of a larger programme of vaccine development against schistosomiasis japonica (Philippines) and schistosomiasis mansoni, attempts have been made to induce resistance to first infection, or to reinfection, in mice by a variety of manipulations.…”

Section: Introductionmentioning

confidence: 99%

Attempts to induce resistance in mice to Schistosoma japonicum and Schistosoma mansoni by exposure to crude schistosome antigens plus cloned glutathione‐S‐transferases

Mitchell¹,

Davern²,

Wood³

et al. 1990

Immunology & Cell Biology

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Summary Several attempts have been made to induce resistance in mice to Schistosoma japonicum (Philippines) or Schistosoma mansoni by exposure to living male and/or female adult worms, their antigens or irradiated cercariae. No resistance was demonstrated in the following cases: re-exposure of mice to cercariae following praziquantel (PZQ) treatment of existing infection; re-exposure of mice following cyclosporin A (CsA) treatment at the time of first cerearial exposure; subcutaneous or intraperitoneal deposition of living male or female worms; repeated intranasal administration of crude worm homogenates plus Bordetella pertussis vaccine (BPV) as adjuvant. Homologous ^^Co-irradiated cercariae were very effective at inducing resistance to infection with 5. mansoni but not to infection with S. japonicum (Philippines) in a limited series of experiments. A regime of infection, immunization with homologous Escherichia co//-derived glutathione-S-transferases (GST), then PZQ treatment followed by homologous re-exposure did not result in significant resistance in either the 5. mansoni or the S. japonicum (Philippines) systems. Mice given irradiated cercariae plus GST were not more resistant to subsequent 5. mansoni infection than mice given irradiated cercariae alone. The results generally confirm and extend those reported by others with the conclusion that resistance to schistosomes in mice is difficult to achieve by exposure to adult worm antigens alone. Moreover, additional immunization with the GST available to date as cloned gene products, and injected in Freund's complete adjuvant, does not influence the outcome of exposure to crude worm antigens including any additive effects of protective irradiated cercariae.

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Schistosome vaccines

Cited by 18 publications

References 54 publications

A theoretical framework for the immunoepidemiology of blocking antibodies to helminth infection

A theoretical framework for the immunoepidemiology of blocking antibodies to helminth infection

Cross-Reactivity ofSchistosoma mansoniCytosolic Superoxide Dismutase, a Protective Vaccine Candidate, with Host Superoxide Dismutase and Identification of Parasite-Specific B Epitopes

Attempts to induce resistance in mice to Schistosoma japonicum and Schistosoma mansoni by exposure to crude schistosome antigens plus cloned glutathione‐S‐transferases

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