Immune events associated with protection in C57BL/6 mice immunized with anti-idiotypic antibodies mimicking protective antigens shared between gamma-irradiated cercariae vaccine and human resistance model of Schistosoma haematobium.

Immunoregulation is central for successful manipulation of schistosomiasis. Unlike schistosome vaccine development strategies that relied on direct selection of antigens from crude responses leading to selection of mildly protective antigens, the present study tested the utility of selection of potentially protective antigens encompassed rounds of immunoregulation via idiotypic network. Anti-idiotypic antibodies (Ab2) were purified from sera of New Zealand white rabbits multiply immunized with gamma-irradiated cercariae of S. haematobium, using adult worm specific idiotypes (Ab1) purified from sera of subjects resistant to reinfection. Ab2 was used for immunization of C57BL/6 mice and consequences of immunization were monitored before and after challenge infection with S. haematobium. Results showed an increase of splenic T cell expression of intercellular adhesion molecule-1 (ICAM-1) and very late antigen-4 (VLA-4) upon immunization (average % stimulated cells 54.9 vs. 20.4, P < 0.05 for ICAM-1 and 31.1 vs. 6.6, P < 0.01 for VLA-4) and challenge, especially at day 6 (83.5 vs. 45.6, P < 0.01) for ICAM-1 and day 10 (50.4 vs. 20.8, P < 0.05) for VLA-4. Thereafter, both adhesion molecules declined at day 28 through 90. Similarly, lymphoproliferation was manifested upon immunization (OD570-630 0.27 vs. 0.09, P < 0.01) and challenge at day 6 (0.5 vs. 0.17, P < 0.01) through day 10 (0.49 vs.0.18, P < 0.05), then declined at day 28 through 90. Moreover, sera of Ab2-immunized mice exhibited an anti-anti-ids (Ab3) reactivity against antigens of approximate molecular weight 40, 80 and 160 kDa of adult worms, which were also recognized by Ab1. However, in contrast to Ab1, Ab3 showed no surface binding to 3 hr schistosomula. Strikingly, mice immunized with Ab2 showed strong resistance to challenge infection (approximately 82% reduction in worm burden, P < 0.001). Taking all, this alternative vaccine development strategy appears to filter out non-protective antigens. Indeed Ab3 recognizes much fewer numbers of antigens, which passed through two rounds of immune regulation. These antigens appear to represent a significant proportion of the protective response in the gamma-irradiated cercariae vaccine and human resistance model as well, providing the basis for an alternative vaccine for schistosomiasis.