CD8+ T effector memory cells protect against liver-stage malaria
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 vaccin...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
2011
|
| _version_ | 1826297047769153536 |
|---|---|
| author | Reyes-Sandoval, A Wyllie, D Bauza, K Milicic, A Forbes, E Rollier, C Hill, A |
| author_facet | Reyes-Sandoval, A Wyllie, D Bauza, K Milicic, A Forbes, E Rollier, C Hill, A |
| author_sort | Reyes-Sandoval, A |
| collection | OXFORD |
| description | 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 (TEM), 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 TEM response that requires long intervals for an efficient boost. A preferential TEM phenotype was maintained in liver, blood, and spleen after Ad/MVA prime-boost regimens, and animals were protected against malaria sporozoite challenge. Blood CD8+ TEM 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 Agspecific TEM cells was confirmed by transfer experiments into naive recipient mice. Thus, we identify persistent CD8 TEMpopulations as essential for vaccine-induced pre-erythrocytic protection against malaria, a finding that has important implications for vaccine design. Copyright © 2011 by The American Association of Immunologists, Inc. |
| first_indexed | 2024-03-07T04:25:40Z |
| format | Journal article |
| id | oxford-uuid:cc84a91e-c13c-43b7-b169-b8deec8200dd |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T04:25:40Z |
| publishDate | 2011 |
| record_format | dspace |
| spelling | oxford-uuid:cc84a91e-c13c-43b7-b169-b8deec8200dd2022-03-27T07:22:37ZCD8+ T effector memory cells protect against liver-stage malariaJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:cc84a91e-c13c-43b7-b169-b8deec8200ddEnglishSymplectic Elements at Oxford2011Reyes-Sandoval, AWyllie, DBauza, KMilicic, AForbes, ERollier, CHill, AIdentification 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 (TEM), 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 TEM response that requires long intervals for an efficient boost. A preferential TEM phenotype was maintained in liver, blood, and spleen after Ad/MVA prime-boost regimens, and animals were protected against malaria sporozoite challenge. Blood CD8+ TEM 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 Agspecific TEM cells was confirmed by transfer experiments into naive recipient mice. Thus, we identify persistent CD8 TEMpopulations as essential for vaccine-induced pre-erythrocytic protection against malaria, a finding that has important implications for vaccine design. Copyright © 2011 by The American Association of Immunologists, Inc. |
| spellingShingle | Reyes-Sandoval, A Wyllie, D Bauza, K Milicic, A Forbes, E Rollier, C Hill, A CD8+ T effector memory cells protect against liver-stage malaria |
| title | CD8+ T effector memory cells protect against liver-stage malaria |
| title_full | CD8+ T effector memory cells protect against liver-stage malaria |
| title_fullStr | CD8+ T effector memory cells protect against liver-stage malaria |
| title_full_unstemmed | CD8+ T effector memory cells protect against liver-stage malaria |
| title_short | CD8+ T effector memory cells protect against liver-stage malaria |
| title_sort | cd8 t effector memory cells protect against liver stage malaria |
| work_keys_str_mv | AT reyessandovala cd8teffectormemorycellsprotectagainstliverstagemalaria AT wyllied cd8teffectormemorycellsprotectagainstliverstagemalaria AT bauzak cd8teffectormemorycellsprotectagainstliverstagemalaria AT milicica cd8teffectormemorycellsprotectagainstliverstagemalaria AT forbese cd8teffectormemorycellsprotectagainstliverstagemalaria AT rollierc cd8teffectormemorycellsprotectagainstliverstagemalaria AT hilla cd8teffectormemorycellsprotectagainstliverstagemalaria |