Practical and ethical issues in the development of a vaccine against schistosomiasis mansoni.

Todd, Charles W.; Colley, Daniel G.

doi:10.4269/ajtmh.2002.66.348

Cited by 33 publications

(24 citation statements)

References 101 publications

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“…A better understanding of the immunologic components involved in the development of protection against infection is needed to lay the foundation for the advancement of efficacious vaccines (49). A common finding in many studies is that a high concentration of serum parasite-specific immunoglobulin E (IgE) is related to resistance against schistosomes (6,12,13,27,39).…”

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Correlation between Eosinophils and Protection against Reinfection withSchistosoma mansoniand the Effect of Human Immunodeficiency Virus Type 1 Coinfection in Humans

et al. 2006

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Longitudinal investigations of an adult male population of Kenyan car washers who have heavy and quantifiable occupational exposure to Schistosoma mansoni cercariae revealed that some individuals develop resistance to reinfection while others remain highly susceptible. We sought to characterize immune correlates associated with host protection in this population. Previous studies have demonstrated an association of peripheral eosinophilia with resistance to reinfection with schistosomes. Thus, we investigated the relationship between the percentage of circulating eosinophils and the effect of human immunodeficiency virus type 1 (HIV-1) coinfection on the susceptibility of the car washers to reinfection with schistosomes. Elevated percentages of circulating eosinophils were associated with resistance to reinfection by S. mansoni in HIV-1-seronegative persons. In the HIV-1-seropositive cohort, low CD4؉ -T-cell counts were associated with a less intense eosinophilia. Moreover, eosinophils from the car washers expressed high levels of Fc⑀RI ␤ chain, a molecule important in immunoglobulin E (IgE)-mediated immunity. Levels of Fc⑀RI ␤ chain expression correlated with serum levels of total and antigen-specific IgE for HIV-1-negative car washers, but this was not the case for individuals coinfected with HIV-1. Overall, these data further implicate eosinophils as having a potential role in development of protective immunity against schistosomes and suggest that changes associated with HIV-1 coinfection increase susceptibility to reinfection.Schistosomes are parasitic trematodes responsible for causing disease in over 200 million people worldwide (14). A better understanding of the immunologic components involved in the development of protection against infection is needed to lay the foundation for the advancement of efficacious vaccines (49). A common finding in many studies is that a high concentration of serum parasite-specific immunoglobulin E (IgE) is related to resistance against schistosomes (6,12,13,27,39). However, whether IgE is directly involved in protective mechanisms in vivo has not been elucidated, as IgE exerts its effector function through Fc⑀RI-expressing cells. Several studies have demonstrated an association between eosinophilia and host protection against schistosomes (2, 18, 45), although whether eosinophils express the high-affinity IgE receptor remains under debate (1,3,4,17,21,23,26,40,42,43). Purified human eosinophils are cytotoxic to schistosomula in vitro in the presence of parasite-specific IgE, with eosinophils from helminthinfected individuals having greater potency (11,16,23,50). These observations suggest that IgE and eosinophils are likely to have an important role in host protection against schistosomes.Our laboratory is conducting a longitudinal study on Schistosoma mansoni infections in a cohort of adult male Kenyan car washers who are occupationally exposed to infective cercariae in the waters along the shores of Lake Victoria (22). Over 200 men in this group have been actively monito...

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Correlation between Eosinophils and Protection against Reinfection withSchistosoma mansoniand the Effect of Human Immunodeficiency Virus Type 1 Coinfection in Humans

et al. 2006

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“…Nevertheless, in a subset of chronically infected patients, this process of ''endogenous desensitization'' or ''immune down-modulation'' is defective or inadequate, which may allow the disease to progress to the severe hepatosplenic form (5). Therefore, identifying mechanisms that facilitate immune down-modulation in schistosomiasis is critical to fully understanding pathogenesis and could ultimately provide new strategies for vaccine development (6,7).…”

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IL-13 receptor α 2 down-modulates granulomatous inflammation and prolongs host survival in schistosomiasis

Mentink‐Kane

Cheever

Thompson

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

124

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An important feature of many chronic parasitic infections is the ability of the invading pathogen and host to establish a compromise, which ensures successful parasitism without killing the infected host. For many helminth infections, down-modulating the immune response is critical because persistent inflammation can become more damaging to the host than the invading pathogen itself. Such is the case with schistosomiasis mansoni, where chronic granulomatous inflammation in the liver causes portal hypertension, porto-pulmonary shunting, bleeding from collateral bypass vessels, and eventual death if not suppressed effectively. CD4 ؉ T helper type 2 cells (Th2) (secreting IL-4, IL-5, and IL-13) characterize the host response after Schistosoma mansoni infection, and recent studies have identified IL-13 as the principal mediator of hepatic fibrosis. Here, we show that the IL-13 receptor ␣ 2 (IL-13R␣2) is a critical mediator of immune down-modulation, identifying the receptor as a life-sustaining off signal for chronic and pernicious inflammation in schistosomiasis.

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“…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.…”

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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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Practical and ethical issues in the development of a vaccine against schistosomiasis mansoni.

Cited by 33 publications

References 101 publications

Correlation between Eosinophils and Protection against Reinfection withSchistosoma mansoniand the Effect of Human Immunodeficiency Virus Type 1 Coinfection in Humans

Correlation between Eosinophils and Protection against Reinfection withSchistosoma mansoniand the Effect of Human Immunodeficiency Virus Type 1 Coinfection in Humans

IL-13 receptor α 2 down-modulates granulomatous inflammation and prolongs host survival in schistosomiasis

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

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