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Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and
Biomedical Research Institute, Rockville, MD 20852
A fundamental obstacle to vaccine development in schistosomiasis
mansoni is a lack of understanding of what type of an immune response
should be invoked. We have addressed this central issue by using the
radiation-attenuated cercariae vaccine in mice genetically engineered
to exhibit highly polarized type 1 (IL-10/IL-4-deficient) or type 2
(IL-10/IL-12-deficient) cytokine and Ab phenotypes. Our data show that
while significant differences in immunity exist after a single
vaccination with irradiated cercariae in double cytokine-deficient vs
wild-type mice, these differences disappear after two vaccinations. The
most important finding of these studies, however, was revealed in
vaccinated IL-10-deficient mice. These mice developed a mixed and
elevated type 1- and type 2-associated immune response and developed
anti-schistosome immunity at levels equal to or better than those
in wild-type mice. This immunity in IL-10-deficient mice correlated
with higher parasite-specific Ab titers, greater proliferative capacity
of lymphocytes, increased frequency of IFN-
- and IL-4-secreting
cells, elevated perivascular/peribronchial inflammatory responses in
the lung, and greater in vitro schistosomulacidal capacity of parasite
Ag-elicited cells. These results suggest that optimal vaccine-induced
immunity against schistosomes is linked not to the development of a
highly polarized response, but, rather, to the induction of both type
1- and type 2-associated immune responses.
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M. G. Chiaramonte, M. Hesse, A. W. Cheever, and T. A. Wynn CpG Oligonucleotides Can Prophylactically Immunize Against Th2-Mediated Schistosome Egg-Induced Pathology by an IL-12-Independent Mechanism J. Immunol., January 15, 2000; 164(2): 973 - 985. [Abstract] [Full Text] [PDF]
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