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Researches On Vaccine Adjuvants For Anti-idiotypic Antibody Of Schistosomiasis

Posted on:2003-08-23Degree:DoctorType:Dissertation
Country:ChinaCandidate:S G ZhongFull Text:PDF
GTID:1104360065460890Subject:Pathogen Biology
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Schistosomiasis remains a significant health problem worldwide. Rapid reinfection following treatment demands frequent retreatment, makes the chemotherapy approach expensive and chemotherapy cannot prevent reinfection. Moreover, some schistosome strains of praziquantel-resistant or decreased susceptibility to the drug have been observed recently in several countries. Therefore, it emphasizes the need for a more long-term approach. To develop a Schistosomiasis vaccine may be one of cheap and efficacious approaches. Researches of Schistosomiasis vaccines have gone more than 60 years, approximately including from the stages of dead vaccine and live vaccine (irradiated attenuated cercariae vaccine) to gene engineered vaccine, etc. Many different forms of vaccines have been tested in animal models, including gluthathione S-transferase, paramyosin, IrV-5, triose phosphate isomerase, Sm23, fatty acid binding protein; which were considered promising by WHO/TDR. But none of them steadily accomplished the pre-set target level of 40% protection. In order to enhance the protective capacity further, it is essential to develop novel vaccine antigens and/or vaccine adjuvants. It has been estimated that a reduction in worm intensity of 50% or more would significantly reduce pathology and degree of morbidity, and decrease transmission rates.Guan et al (1991) established a strain of monoclonal anti-idiotypic antibody NP30 ofSchistosomajaponicum, which is an internal image anti-idiotypic antibody of gut associated antigen (GAA ), its antibodyisotype is IgM. NP30 has a partial cross reaction with soluble egg antigen (SEA) and membrane associated antigen (MAA). NP30 molecule has been researched on many aspects. It has been confirmed that NP30 has sensitizing effect on formation of hepatic egg granulomas in mouse model for hepatic egg granuloma of Schistosoma japonicum; immunization with NP30 in Kunming mice, C57BL/6 mice and goats obtained worm reduction of 50.46% , 41.67% and 42.78%, respectively. NP30 possesses effects of both anti-fecundity and anti-embryonation immunity on female worms of S. japonicum. Moreover, NP30 plays a significant down-modulatory role to hepatic granuloma and fibrosis (the diameter, area and volume of egg granuloma were all significantly less than those of control; the contents of type I , III of collagen and fibronectin were also significantly less than those of control). Anti-idiotypic antibody NP30 was confirmed with protective immunity of both anti-infection and anti-pathology and may act as a vaccine candidate for schistosomiasis japonica. On these bases, the aim of this study was to develop effective adjuvants for enhancing protective immunity of NP30, we performed a series of researches on nanoparticles, cytokines and traditional Chinese medicines, including their effector mechanisms.1. Calcium Nanoparticles as Vaccine Adjuvant of Anti-idiotypic Antibody for Schistosomiasis1. 1 Determine Whether Calcium Nanopart i c I es Can Act as a Vaccine Adjuvant of Anti-idiotypic Antibodyfor SchistosomiasisFirst, we prepared calcium nanaparticles (CA) by physical method,its diameter is 300-800 nm. Second, CA-NP30 conjugate was made by binding CA with NP30. Then immunized BALB/c mice with CA-NP30, and evaluated its effects on protective immunity, serum specific IgG antibody levels and delayed type hypersensitivity (judged by footpad test).Both sexes of 6-8 week old (weight 18-22 g ) BALB/c mice were randomly divided into 4 groups of 10 mice each. (1)The experimental group: Mice were immunized 3 times, separated by 2-week intervals, by intraperitoneal injection of CA-NP30 (CA and NP30 each 20? g/dose/mouse). Eight weeks after final boosting, vaccinated and control mice were challenged percutaneously with 40 ?1 S. japonicum cercariae (Chinese mainland strain) by the cover glass method. Recovery of adult worms was carried out by portal perfusion at 6 weeks after challenge infection and hepatic tissue egg counts were performed. The worm and egg reductions were calculated. Serum s...
Keywords/Search Tags:Schistosomiasis, Anti-idiotypic antibody, Vaccine adjuvant, Nanoparticles, Cytokine, Traditional Chinese medicine, Protection ratio
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