Whether by administration of a vaccine or anti-pathogenesis substances, intervention of schistosomiasis by immunologic means is a major goal of schistosomiasis research efforts today. This application is to renew our program examining the role Schistosoma mansoni irradiated cercariae play as a model for inducing anti-schistosome immunity and anti-pathogenesis, and as candidates for a live vaccine. To determine vaccine effectiveness in situations approximating that to be encountered in the field, immunity will be assessed aginst multiple 'trickle' cercarial challenges. Using mice immunized with irradiated Schistosma japonicum cercariae, the specificity of vaccine induced resistance will be more thoroughly examined by challenge with the homologous or a heterologous schistsome species (S. mansoni). Anti-pathogenic effects of live vaccine administration will be examined in the mouse, along with the possibility that immunologic suppression of protection develops in cases where suboptimal levels of immunity are stimulated. Basic issues related to a recently developed cryopreserved live vaccine will also be addressed. These are: (1) by autoradiographic techniques determine the vaccine's migratory properties in the naive host, and (2) Attempt to enhance the vaccine's efficiency by concurrent administration of immunopotentiators and the cryopreserved vaccine. These experiments should answer pressing questions related to anti-schistosome immune mechanisms, while evaluating more critically the feasibility of irradiated larve as components of a live vaccine.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Unknown (R22)
Project #
2R22AI016006-07
Application #
3444507
Study Section
Tropical Medicine and Parasitology Study Section (TMP)
Project Start
1979-09-30
Project End
1988-08-31
Budget Start
1985-09-01
Budget End
1986-08-31
Support Year
7
Fiscal Year
1985
Total Cost
Indirect Cost
Name
American Foundation for Biological Research
Department
Type
DUNS #
City
Rockville
State
MD
Country
United States
Zip Code
20852
Dean, D A; Mangold, B L; Lewis, F A (1995) Comparison of two strains of Schistosoma mansoni with respect to the sites and kinetics of immune elimination in irradiated cercaria-immunized mice. J Parasitol 81:43-7
Pearce, E J; Caspar, P; Grzych, J M et al. (1991) Downregulation of Th1 cytokine production accompanies induction of Th2 responses by a parasitic helminth, Schistosoma mansoni. J Exp Med 173:159-66
Lewis, F A; White-Ziegler, C A; Ball, J E et al. (1990) Schistosoma mansoni larvicidal activity of murine bronchoalveolar lavage cells. Infect Immun 58:3903-8
Cooper, L A; Lewis, F A; File-Emperador, S (1989) Re-establishing a life cycle of Schistosoma mansoni from cryopreserved larvae. J Parasitol 75:353-6
Ward, R D; Lewis, F A; Yoshino, T P et al. (1988) Schistosoma mansoni: relationship between cercarial production levels and snail host susceptibility. Exp Parasitol 66:78-85
Lewis, F A; Winestock, J; Dingaan, B et al. (1987) Intraspecific cross-protection in mice immunized with irradiated Schistosoma mansoni cercariae. J Parasitol 73:787-91
Lewis, F A; Kennell, C J; James, S L (1987) Vaccine-induced immunity in mice against Schistosoma mansoni trickle cercarial infections. Am J Trop Med Hyg 37:98-105
Lewis, F A; Winestock, J; James, S L (1987) Macrophage activation as an immune correlate to protective immunity against schistosomiasis in mice immunized with an irradiated, cryopreserved live vaccine. Infect Immun 55:1339-45
Lewis, F A; Stirewalt, M (1985) Effect of a cryopreserved live vaccine on resistance in mice with a pre-existing Schistosoma mansoni infection. Am J Trop Med Hyg 34:341-5
Lewis, F A; Hieny, S; Sher, A (1985) Evidence against the existence of specific Schistosoma mansoni subpopulations which are resistant to irradiated vaccine-induced immunity. Am J Trop Med Hyg 34:86-91