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In Vitro Praziquantel - Attenuated Cercariae and Schistosomula: A Novel Approach Towards The Development Of Anti-Schistosome Vaccine

1Laila H. El-Sayed, 1Ghoneim H.M., 1Demian S.R., 1Nagwa M. Tawfik, 1El-Sayed M.H., 2Mastino A., and 3Abou Rawash N.M.

Departments of 1Immunology and 3Biochemistry, Medical Research Institute, Alexandria University and 2Department of Experimental Medicine and Biochemical Sciences, University of Rome, tor Vergata, Rome, Italy.

This article describes a new anti-schistosome vaccine design using the putative anti-parasite drug “praziquantel” (PZQ) for in vitro larval attenuation. Resistance to S. mansoni reinfection after immunization with PZQ-attenuated cercariae and schistosomula was evaluated. The results revealed that the drug has direct effects on the morphology of both cercariae and schistosomula including cercarial tail loss, violent contractions and reduced motility after incubation with different drug concentrations. These morphological alterations were associated with significant impairment of the larval maturation capacity with the result that few or no worms were recovered from mice injected with PZQ-treated parasites. It seems likely that dead and dying PZQ-attenuated larvae elicit strong protective immunity in vaccinated mice manifested by significant reduction in worm burdens of challenge cercarial infection. The schistosomula induced higher protection than cercariae in this context. The best vaccine regimen was obtained in mice injected twice at 4 weeks intervals with 200 schistosomula attenuated in vitro by treatment with 0.01 mg PZQ/ml for 3 hours and challenged 4 weeks after second injection. Vaccine potential of PZQ-attenuated schistosomula was also higher in inbred than outbred murine strains and gave significant protection than two of the conventional schistosome vaccines (ultraviolet-irradiated cercariae and soluble adult worm extract). The reduction in worm burden after vaccination with in vitro PZQ-attenuated schistosomula was associated with significant impairment of female adult worm fecundity.

 



This work was funded by the Schistosomiasis Research Program (SRP).

corresponding author: dr. Laila H. El-Sayed, Medical Research Institute, 165 El-Horreya avenue, El-Hadra, Alexandria