Schistosoma mansoni egg granuloma size reduction in challenged baboons after vaccination with irradiated cryopreserved schistosomula.

Abstract

Young male baboons born in captivity were immunized with an attenuated, cryopreserved schistosomular vaccine derived from gamma-irradiated (50 krad) cercariae of the Puerto Rican strain of Schistosoma mansoni. Protection against a heterologous Kenyan strain of S. mansoni, after percutaneous infection, was assessed. Partial protection (33-53% reduction in worm burden) was obtained in three of six vaccinated-challenged baboons, an unremarkable result. Of greater interest was the fact that all six unvaccinated-challenged control baboons, but only one of the six vaccinated-challenged baboons, had macroscopic egg granulomas on their liver surfaces. This difference in granuloma size was substantiated by measuring hepatic and colonic granulomas. The mean (+/- SEM) hepatic and colonic granuloma diameters for the six unvaccinated baboons were 406 +/- 38 micron and 313 +/- 27 micron, respectively, and for the five "typical" vaccinated-challenged baboons the mean diameters were 283 +/- 27 micron and 202 +/- 23 micron, respectively. Both hepatic and colonic granulomas were significantly smaller in the five typical vaccinated-challenged baboons. Not only did the exceptional vaccinated-challenged baboon have very large hepatic and colonic granulomas, but also it was the only one of its group whose mesenteric lymph node cells were not suppressed in their in vitro proliferative response to a schistosome antigen. These results strongly suggest that granuloma size reduction in the majority of the vaccinated baboons was the result of immunoregulation--i.e., the small postvaccination granulomas were "modulated." Despite their small size, hepatic granulomas in the typical vaccinated baboons were apparently as effective in sequestering egg toxins and preventing hepatocyte damage as the larger granulomas of the control baboons. Smaller, less obstructive granulomas are thought to be more beneficial to the host than large, vigorous granulomas, with respect to lessening chronic disease. The present results give encouragement that a vaccine to ameliorate disease in human schistosomiasis is possible. This effect should add to the attractiveness of partial protection against challenge infections conferred by attenuated larval vaccines, as reported by others, to yield a dually beneficial vaccine for human use.