CD8+ T effector memory cells protect against liver-stage malaria.

Reyes-Sandoval, A; Wyllie, D; Bauza, K; Milicic, A; Forbes, E; Rollier, C; Hill, A

Journal article

CD8+ T effector memory cells protect against liver-stage malaria.

Abstract:: Identification of correlates of protection for infectious diseases including malaria is a major challenge and has become one of the main obstacles in developing effective vaccines. We investigated protection against liver-stage malaria conferred by vaccination with adenoviral (Ad) and modified vaccinia Ankara (MVA) vectors expressing pre-erythrocytic malaria Ags. By classifying CD8(+) T cells into effector, effector memory (T(EM)), and central memory subsets using CD62L and CD127 markers, we found striking differences in T cell memory generation. Although MVA induced accelerated central memory T cell generation, which could be efficiently boosted by subsequent Ad administration, it failed to protect against malaria. In contrast, Ad vectors, which permit persistent Ag delivery, elicit a prolonged effector T cell and T(EM) response that requires long intervals for an efficient boost. A preferential T(EM) phenotype was maintained in liver, blood, and spleen after Ad/MVA prime-boost regimens, and animals were protected against malaria sporozoite challenge. Blood CD8(+) T(EM) cells correlated with protection against malaria liver-stage infection, assessed by estimation of number of parasites emerging from the liver into the blood. The protective ability of Ag-specific T(EM) cells was confirmed by transfer experiments into naive recipient mice. Thus, we identify persistent CD8 T(EM) populations as essential for vaccine-induced pre-erythrocytic protection against malaria, a finding that has important implications for vaccine design.

Publication status:: Published

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APA Style

Reyes-Sandoval, A., Wyllie, D., Bauza, K., Milicic, A., Forbes, E., Rollier, C., & Hill, A. (2011). CD8+ T effector memory cells protect against liver-stage malaria. Journal of Immunology, 187(3), 1347–1357.

MLA Style

Reyes-Sandoval, A., et al. “CD8+ T Effector Memory Cells Protect against Liver-Stage Malaria.” Journal of Immunology, vol. 187, no. 3, 2011, pp. 1347–57.

Chicago Style

Reyes-Sandoval, A, D Wyllie, K Bauza, A Milicic, E Forbes, C Rollier, and A Hill. 2011. “CD8+ T Effector Memory Cells Protect against Liver-Stage Malaria.” Journal of Immunology 187 (3): 1347–57.
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