Schistosomiasis is a health problem of major proportions in many of the developing countries of the world. Combined with other community-wide control measures now available, an effective vaccine would have significant impact in limiting this parasitic infection. A great deal of evidence in experimental models support the contention that although immune induction occurs by classical antigen-specific means, actual effector mechanisms, which may be relatively non-antigen specific, play large roles in challenge parasite attrition. In part the work proposed here is designed to better define vaccine candidates which preferentially stimulate T cell responses leading to resistance. Using mice immunized with irradiated Schistosoma mansoni cercariae, advantage will be taken of the technology for immortalizing antigen-reactive T cells, by T cell cloning procedures, to examine T cell reactivity, define relevant antigens, and determine the functional significance of such T cell reactivity. Experiments will also be conducted to examine larvacidal activity of cells isolated from the lungs of immune mice, in hopes of better defining their potential participation in eliminating challenge infections. In addition, some of the parameters for immune induction and effector mechanisms that have been worked out for the S. mansoni model in the mouse will be expanded to include experiments with the related species, S. japonicum. The overall goal of these experiments will be to speed the development of a safe and effective vaccine by better defining the mechanisms leading to resistance to both S. mansoni and S. japonicum.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Unknown (R22)
Project #
5R22AI016006-12
Application #
3566936
Study Section
Tropical Medicine and Parasitology Study Section (TMP)
Project Start
1979-09-30
Project End
1992-03-31
Budget Start
1991-04-01
Budget End
1992-03-31
Support Year
12
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Biomedical Research, Inc.
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