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Vaccine. 2009 Oct 19;27(44):6103-6. doi: 10.1016/j.vaccine.2009.08.025. Epub 2009 Aug 25.

CD8 T cell immunity to Plasmodium permits generation of protective antibodies after repeated sporozoite challenge.

Author information

1
Department of Microbiology, University of Iowa, Iowa City, IA 52242, United States.

Abstract

Individuals living in malaria endemic areas are subject to repeated infections yet fail to develop sterilizing immunity, however, immunization of mice with attenuated sporozoites or subunit vaccines has shown the ability to protect mice against a sporozoite challenge. We recently reported that mice primed with dendritic cells coated with the dominant circumsporozoite CD8 T cell epitope from Plasmodium berghei followed by a boost with recombinant Listeria monocytogenes expressing the same epitope exhibited sterile immunity against a sporozoite challenge for more than one year. In this report we show those mice do not contain protective antibodies and that depletion of CD4 T cells in the immunized mice did not affect sterile immunity. In contrast, CD8 T cell depletion eliminated protection. Thus, protective immunity generated by this immunization approach is entirely memory CD8 T cell-dependent. We also show here that mice initially protected by circumsporozoite-specific memory CD8 T cells develop sterilizing sporozoite-specific antibodies after repeated asymptomatic challenges with physiologic numbers of viable sporozoites. Therefore, initial protection by a CD8 T cell-targeted liver stage subunit vaccine allows the generation of enhanced sterilizing immune responses from repeated exposure to Plasmodium parasites.

PMID:
19712771
PMCID:
PMC2759845
DOI:
10.1016/j.vaccine.2009.08.025
[Indexed for MEDLINE]
Free PMC Article

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