†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