Protective Potential of Antioxidant Enzymes as Vaccines for Schistosomiasis in a Non-Human Primate Model

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.

Papain‐Based Vaccination Modulates Schistosoma mansoni Infection‐Induced Cytokine Signals

“…mansoni attempted to counteract the infection‐induced hyporesponsiveness by eliciting strong type 1‐biased immune responses, via experimental host immunization with parasite tegument‐associated or ESP molecules in a plasmid cDNA construct or in conjunction with type 1 adjuvants. The resultant protection was consistently limited . We have proposed that the S .…”

“…Vaccination against challenge S. mansoni attempted to counteract the infection-induced hyporesponsiveness by eliciting strong type 1-biased immune responses, via experimental host immunization with parasite tegumentassociated or ESP molecules in a plasmid cDNA construct or in conjunction with type 1 adjuvants. The resultant protection was consistently limited [26,27]. We have proposed that the S. mansoni -induced immunologic stalemate should be deviated towards a preponderant type 2, not type 1, immune phenotype, in an aim to recruit, engage, and activate basophils and eosinophils, the mightiest immune effectors in the chase of developing larvae in the dermis, lung capillaries and liver sinusoids.…”

Visit to intensive care of 2050

“…antioxidants, anti-inflammatory agents) [15][16][17][18] into improved outcomes of critically ill patients. This issue has gradually been overcome with mandatory antioxidant vaccination programs [19] and the correction of mitochondrial damage on location by emergency medical services [20], allowing intensive care medicine to focus on supportive care rather than late "metabolic and immune damage control".…”

Antioxidants and Vaccines

“…Many reports reveal the role of antioxidants as vaccines or ameliorating vaccine-induced adverse effects. Fruits and vegetable are rich in vitamins, and hence intake of adequate amount of these food items by the pediatric population at the period of vaccination is advisable [4][5][6][7][8][9].…”