Abstract
Schistosomiasis remains a major cause of morbidity in the world. The challenge today is not so much in the clinical management of individual patients, but rather in population-based control of transmission in endemic areas. Despite recent large-scale efforts, such as integrated control programs aimed at limiting schistosomiasis by improving education and sanitation, molluscicide treatment programs and chemotherapy with praziquantel, there has only been limited success. There is an urgent need for complementary approaches, such as vaccines. We demonstrated previously that anti-oxidant enzymes, such as Cu–Zn superoxide dismutase (SOD) and glutathione S peroxidase (GPX), when administered as DNA-based vaccines induced significant levels of protection in inbred mice, greater than the target 40% reduction in worm burden compared to controls set as a minimum by the WHO. These results led us to investigate if immunization of non-human primates with antioxidants would stimulate an immune response that could confer protection as a prelude study for human trials. Issues of vaccine toxicity and safety that were difficult to address in mice were also investigated. All baboons in the study were examined clinically throughout the study and no adverse reactions occurred to the immunization. When our outbred baboons were vaccinated with two different formulations of SOD (SmCT-SOD and SmEC-SOD) or one of GPX (SmGPX), they showed a reduction in worm number to varying degrees, when compared with the control group. More pronounced, vaccinated animals showed decreased bloody diarrhea, days of diarrhea, and egg excretion (transmission), as well as reduction of eggs in the liver tissue and in the large intestine (pathology) compared to controls. Specific IgG antibodies were present in sera after immunizations and 10 weeks after challenge infection compared to controls. Peripheral blood mononuclear cells, mesenteric, and inguinal node cells from vaccinated animals proliferated and produced high levels of cytokines and chemokines in response to crude and recombinant antigens compared with controls. All together, these data demonstrate the potential of antioxidants as a vaccine in a non-human primate model.
Highlights
Schistosomiasis remains a major cause of morbidity in the world
Our laboratory has demonstrated that vaccination of inbred mice with naked DNA constructs containing Cu/Zn cytosolic superoxide dismutase (CT-SOD), signal-peptide containing SOD (EC-SOD), or glutathione peroxidase (GPX) derived from S. mansoni showed significant levels of protection compared to a control group [29]
Our murine results encouraged us to investigate if immunization of non-human primates with these antioxidants would stimulate an immune response that could be correlated with protection as a prelude study for human trials
Summary
Schistosomiasis remains a major cause of morbidity in the world. The disease is endemic in 76 countries of the world where it affects some 200 million people [1]. Substantial research has established that school-aged children in endemic areas are at significant risk of serious disease resulting from infection with schistosomes [2, 3]. Despite recent large-scale efforts, integrated control programs aimed at limiting schistosomiasis by improving education and sanitation, molluscicide treatment programs to reduce the population of the intermediate snail host, and chemotherapy have had limited success [18]. The challenge today is not so much in the clinical management of individual patients, but rather in population-based control of transmission (and of morbidity) in endemic areas. Because current control strategies employing chemotherapy with PZQ have not reduced transmission and morbidity to acceptable levels, there is an urgent need for complementary approaches, such as vaccines for schistosomiasis [20, 21]
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