Studies On The Surface Antigens Of Schistosoma Mansoni
Shah, Jyotosna Sudhir
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The development of a vaccine against schistosomiasis is highly desirable for the control of the disease. Existing drugs used for treatment of the disease have two disadvantages: firstly they may not prevent a reinfection and secondly, they possess some serious side effects. Another possibility of controlling schistosomiasis is through the elimination of snail vector. However, this is an impractical and expensive task in many of the affected countries. Irradiated cercariae have been used in mice as a vaccine against schistosomiasis (Miller and Smithers, 1980). This is not practicable for human schistosomiasis. The infective form of the parasite are the cercariae released into fresh water by the snail vector. During skin penetration cercariae are transformed into schistosomula or young adults. They mature into adult worms which live in the mesenteric veins of the host. Adult worms are resistant to an immune response mounted by the host and at the same time, the host is capable of overcoming further infection by cercariae (Smithers and Terry, 1969). This is referred to as concomitant immunity. It involves the destruction of schistosomula of the challeng infection by the host immune system. In vitro the schistoscmula are killed or damaged by a number of mechanisms involving antibodies and cells (Butterworth, Sturrock, Houba, Mahmoud, Sher and Rees, 1975) or antibody and complement (Clegg and Smithers,1972), or antibody, cells and complement (McLaren and Rarnalho-Pinto, 1979). The antigens on the teguments of the adult worms and schistosomula are important in this process. Hence, a knowledge of surface antigens of the parasite is likely to be important in understanding immunity. Surface proteins on cercariae and schistosomula have been characterized using lactoperoxidase catalysed iodination (Ramasamy, 1979). Possible surface proteins and antigens have been detected on adult worms by Hayunga, Murrell, Taylor and Vannier, (1979 a & b) by radio iodination techniques. However, their techniques may not have involved specific labelling of surface proteins. The surface proteins and the surface antigens on the parasite have been characterized in the Present study . The life cycle of the S. mansoni was maintained in the Department of Biochemistry for part of the study and at Welcome Trust Laboratories, Nairobi for the rest of the study. Snails were infected artificially by the miracidia obtained from eggs present in the feceas qf S. mansoni infected baboons. Cercariae used in the experiments were shed by t;he infected snails. Schistosomula'~ere prepared by the skin penetration ciethod. Adult worms were:ubtained by perfusion of mice, six weeks after infection with cercariae. Surface proteins and glycoproteins were identified by radio- 125 3 labelling of the live parasites, uSlng I and H sodium borohydride respectively. Labelled proteins were extracted in detergent and ana lysed by gel electrophoresis followed by autoradiography. Antigens among the labelled molecules were determined by immuneprecipitation of the extracts with specific antibodies. Methods for studying immunity to infection in mice are also described. Parasites radiolabelled with 125 I using lactoperoxidase catalysed iodination and Bolton-Hunter iodination, were compared. Lactoperoxidase catalysed iodination was found to be superior to Bolton-Hunter iodination for surface labelling. Several labelled proteins were detected on the surface of the adult worms. Glycopropteins on the surface were detected using galactose oxidase and 3H sodium borohydride. Lactoperoxidase was shown to be absorbed onto the surface of the parasite: Some of the proteins labeled on adult worms were also present on schistosomula and cercariae. After the detection of labelled proteins on the surfaces of the parasite, a study of the surface antigens was undertaken. Antigens were detected using rabbit antiserum to freeze-thawed adult worm teguments and sera from patients infected with S. mansoni. Several antigens were detected on the surface of the adult worms by the rabbit antiserum. Some of .the antigens were also present on schistosomula and cercariae. Surface antigens were also detected on all three forms using infected human sera. The presence of common antigens led to the investigation of adult worm teguments as a possible material for imunizing mice and baboons against infection. After immunization with adult worm material, mice or baboons were infected with cercariae and the levels of infection measured after six weeks, by perfusion of mice or baboons to release adult worms. The results showed that complete protection against infection was difficult to achieve in mice and baboons. A study on possible variation of surface antigens on the adult worms of s. mansoni isolated from different geographical regions of Kenya, too was carried out. In such investigations worms obtained from mice infected with cercariae from Kibwezi and Tala Districts and Rusinga Island were used. There was apparently little biological variation in the surface antigens of the worms from the three regions. An investigation was carried out on determining the differences in surface antigens between male and female adult worms. Results showed that there were no detectable differences in the surface antigens of males and females. The study was also extended to investigate whether there were cross-reacting surface antigens on S. mansoni and S. haematobium. Results revealed that some of the surface antigen on S. haematobium detected by rabbit antiserum to S. haematobium adult freeze-thawed antigens also reacted with" the rabbit antiserum to S. mansoni adult freeze-thawed antigens.