Journal
VACCINE
Volume 29, Issue 43, Pages 7335-7342Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2011.07.081
Keywords
Plasmodium; Malaria vaccine; Circumsporozoite protein (CSP); Non-CSP antigens
Categories
Funding
- Bill and Melinda Gates Foundation
- National Institutes of Health [R56 AI073658, R01AI059472]
- GlaxoSmithKline (GSK)
- W.M. Keck Foundation
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Immunization of BALB/c mice with irradiated sporozoites (IrSp) of Plasmodium yoelii can lead to sterile immunity. The circumsporozoite protein (CSP) plays a dominant role in protection. Nevertheless after hyper-immunization with IrSp, complete protection is obtained in CSP-transgenic BALB/c mice that are T-cell tolerant to the CSP and cannot produce antibodies [CSP-Tg/JhT(-/-)]. This protection is mediated exclusively by CD8(+) T cells [1]. To identify the non-CSP protective T cell antigens, we studied the properties of 34 P. yoelii sporozoite antigens that are predicted to be secreted and to contain strong Kd-restricted CD8(+) T cell epitopes. The synthetic peptides corresponding to the epitopes were used to screen for the presence of peptide-specific CD8(+) T cells secreting interferon-gamma (IFN-gamma) in splenocytes from CSP-Tg/JhT(-/-) BALB/c mice hyper immunized with IrSp. However, the numbers of IFN-gamma-secreting splenocytes specific for the non-CSP antigen-derived peptides were 20-100 times lower than those specific for the CSP-specific peptide. When mice were immunized with recombinant adenoviruses expressing selected non-CSP antigens, the animals were not protected against challenge with P. yoelii sporozoites although large numbers of CD8(+). specific T cells were generated. (C) 2011 Elsevier Ltd. All rights reserved.
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