The effect of immunizing Swiss mice with soluble proteins from the intermediate host biomphalaria pfeifferi and challenging them with schistosoma mansoni

Abstract

Schistosomiasis, also known as bilharziasis, is second only to malaria in public health importance. It is estimated that 200 million people worldwide are infected and that 20 000 deaths are associated with the severe consequences of infection. Chemotherapy remains the cornerstone of intervention but rapid re-infection demands frequent re-treatment and emphasizes the need for a more long-term approach. The existence of at least partially protective immunity in exposed humans would make vaccination a logical complement to drug therapy. The administration of radiation-attenuated cercariae to laboratory animals provided protection against experimental S. mansoni infection by blocking the migration of the parasite out of the lung. Great attention has been paid to the use of antigens from schistosomules, with disappointing protection results so far. It is hoped that better success can be achieved using cocktails of recombinant antigens. Common antigens between different species of Schistosoma and their intermediate hosts have been reported. This study was done to investigate the effect of immunizing Swiss mice with soluble proteins from S mansoni vector Biomphalaria pfeifferi and challenging them with S mansoni. The study was done using mice as the models for human schistosomiasis. The mice were divided in four groups, three of which comprised of eighteen mice each and one group (non-infected control) of two mice. The study involved immunization of mice and then challenging them with cercariae of S. mansoni. On day 0 (zero) of the experiment DG (mice immunized with antigens from digestive gland of intermediate host) and RT (mice immunized with antigens from the rest of the tissues of intermediate host) groups were immunized with 50 ug of snail antigens in 100 III of complete Freunds adjuvant intra-peritoneally. In week two and four DG and RT groups of mice were boosted with 50 ug of the snail antigens in 100 III of incomplete Freunds adjuvant. One week after final vaccination, mice in DG, RT and IC (infected control) groups were challenged with cercariae of S. mansoni. In week two and four, six mice from each of the three groups were sampled for cells from the lymph nodes and spleen for cell culture and blood for ELISA. In NC (naive control) group the two mice were sampled for serum only. In Week six, mice from the three groups were: sampled for blood; perfusion was carried out to recover adult worms; their livers tissues were examined for gross pathology and tissues were preserved for histopathology. The results from this study showed that mice immunized with antigens prepared from an intermediate host are better protected than non-vaccinated mice. The mean worm burden was higher in IC group than both RT and DG group of mice. The results also reveal that RT candidate vaccine offered a better protection than DG candidate vaccine. Worm reduction in RT was significantly higher (0.05) at 60.5% than that ofDG that was at 43.3%. In cellular responses, RT significantly stimulated higher production of interferon gamma as compared to [C at all time points. RT interleukin-5 responses were significantly higher than the DG and IC for both 0-3 hr protein release (0-3 hr) and (Schistosome worm antigen preparation) SWAP antigens for both spleen and lymph node. RT produced higher Immunoglobin G (IgG) responses than DG and [C, meaning it killed more worms using antibody dependant cell-mediated Cytotoxicity (ADCC). [n RT, all the mice had slightly inflammed livers. DG mice had slightly inflamed livers except one female member who had an inflamed liver. In IC mice, all the sampled animals had inflammed liver tissues. However, none of the mice in all the groups had granulomas most probably due to delayed pathology development in Swiss mice. In conclusion therefore, although the two vaccine candidates were protective, RT was a better vaccine candidate in terms of higher worm reduction, higher cellular and humoral protective responses and least pathology.