Immunization of baboons with attenuated schistosomula of Schistosoma haematobium: levels of protection induced by immunization with larvae irradiated with 20 and 60 krad

Abstract

We have shown previously that baboons (Papio anubis) develop high levels (greater than 80%) of protection against challenge infection following immunization with Schistosoma haematobium cercariae irradiated with 20 krad. In the present study baboons were immunized with schistosomula irradiated with either 20 krad or 60 krad, with variations in the timing and number of larvae comprising each vaccination. Baboons immunized 2 or 3 times with schistosomula irradiated with 20 krad were significantly more protected (85-90%) against challenge infection than baboons similarly immunized with larvae receiving 60 krad (56-50% protection). Baboons immunized with schistosomula irradiated with 20 krad were better protected against challenge infection at 8 weeks after immunization than at 28 weeks after immunization. Protection was manifest by a reduction in worm numbers, tissue and excreta egg counts, gross pathology and, to a lesser extent, by stability of body weight and haematological indices following challenge. Enzyme-linked immunosorbent assay (ELISA) results of selected baboon sera showed few differences related to irradiation dose alone, but titres were higher in baboons receiving booster immunizations, and there was a significant correlation between titres immediately preceding challenge and the degree of resistance. Examination of responses to individual schistosomular surface antigens by immunoprecipitation and sodium dodecyl sulphate-polyacrylamide gel electrophoresis showed no correlation between the pattern of antigens recognized and resistance status. As with the ELISA assay, an anamnestic response was detected after vaccination, while the amount of antibody present declined markedly with increasing time after individual immunizations.

Homologous and heterologous protective immunity to Egyptian strains of Schistosoma mansoni and S. haematobium induced by ultraviolet‐irradiated cercariae

“…These levels are comparable to those observed previously with Puerto Ricanderived strains of S. mansoni in C57BL/6 mice (Murrell et al 1979, James, Labine & Sher 1981, Lewis & Wilson 1982, Dean et al 1984, Wilson & Coulson 1989, Reynolds & Harn 1992, and in most cases in Balb/c mice (Smith & Clegg 1984, James & Sher 1983, Sher, Hieny & James 1984, Sher et al 1982, although lower levels (22% to 40%) were observed in Balb/c mice in two studies (Ruppel et al 1985, Timothy et al 1992). The levels of homologous immunity to S. haematobium (88% to 99%) are comparable to those observed previously in baboons optimally immunized with irradiated cercariae (64% to 89%, Webbe et al 1982) or with irradiated schistosomula (87% to 93%, Harrison et al 1990). They are generally much higher than those observed previously in mice, however (46% and 53%, Agnew et al 1989;53% and Navarrete et al 1994).…”

Vaccines to combat the neglected tropical diseases

“…The radiation‐attenuated vaccine for S. mansoni has been shown to protect in a variety of host species such as rats (138) and non‐human primates, including baboons and chimpanzees (139, 140). Radiation‐attenuated larvae of S. haematobium induce protection in baboons (141). Over the past 25 years, a substantial inventory of data has accrued which reveals many features of the radiation‐attenuated larvae vaccine that are critical to our understanding of how to induce protective immunity and are well reviewed in Hewitson et al (129).…”

Radiation-attenuated schistosome vaccination – a brief historical perspective

“…In primates, repeated exposures are needed to induce modest to high levels of protection and result in boosting of antigen-specific IgG, levels of which correlate with protection (Harrison et al 1990) ; Soisson et al 1993 ;Yole et al 1996). This indicates that antibody plays a major role in irradiated vaccine immunity in primates.…”