Correlation of memory T cell responses against TRAP with protection from clinical malaria, and CD4^+ CD25 ^high T cells with susceptibility in Kenyans
Background: Immunity to malaria develops naturally in endemic regions, but the protective immune mechanisms are poorly understood. Many vaccination strategies aim to induce T cells against divers pre-erythrocytic antigens, but correlates of protection in the field have been limited. The objective of...
| Main Authors: | , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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Public Library of Science
2008
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| _version_ | 1826296948674527232 |
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| author | Todryk, S Bejon, P Mwangi, T Plebanski, M Urban, B Marsh, K Hill, A Flanagan, K |
| author_facet | Todryk, S Bejon, P Mwangi, T Plebanski, M Urban, B Marsh, K Hill, A Flanagan, K |
| author_sort | Todryk, S |
| collection | OXFORD |
| description | Background: Immunity to malaria develops naturally in endemic regions, but the protective immune mechanisms are poorly understood. Many vaccination strategies aim to induce T cells against divers pre-erythrocytic antigens, but correlates of protection in the field have been limited. The objective of this study was to investigate cell-mediated immune correlates of protection in natural malaria. Memory T cells reactive against thrombospondin-related adhesive protein (TRAP) and circumsporozoite (CS) protein, major vaccine candidate antigens, were measured, as were frequencies of CD4^+ CD25^high T cells, which may suppress immunity, and CD56^+ NK cells and γδ T cells, which may be effectors or may modulate immunity. Methodology and Principal Findings: 112 healthy volunteers living in rural Kenya were entered in the study. Memory T cells reactive against TRAP and CS were measured using a cultured IFNγ ELISPOT appproach, whilst CD4^+ CD25^high T cells were established early in life (<5 years) in contrast to CS, and cultured ELISPOT memory T cell responses did not correlate with ex-vivo IFNγ ELISPOT effector responses. Data was examined for associations with risk of clinical malaria for a period of 300 days. Multivariate logistic analysis incorporating age and CS response showed that cultured memory T cell responses against TRAP were associated with a significantly reduced incidence of malaria (p=0.028). This was not seen for CS responses. Higher numbers of CD4^+ CD25^high T cells, potentially regulatory T cells, were associated with a significantly increased risk of clinical malaria (p=0.039). Conclusions: These data demonstrate a role for central memory T cells in natural malaria immunity and support current vaccination strategies aimed at inducing durable protective T cell responses against the TRAP antigen. They also suggest that CD4^+ CD25^high T cells may negatively affect naturally acquired malarial immunity. |
| first_indexed | 2024-03-07T04:24:10Z |
| format | Journal article |
| id | oxford-uuid:cc0c4d33-6ebf-4c1c-9a6d-ed6e0d4515b3 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T04:24:10Z |
| publishDate | 2008 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | oxford-uuid:cc0c4d33-6ebf-4c1c-9a6d-ed6e0d4515b32022-03-27T07:19:06ZCorrelation of memory T cell responses against TRAP with protection from clinical malaria, and CD4^+ CD25 ^high T cells with susceptibility in KenyansJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:cc0c4d33-6ebf-4c1c-9a6d-ed6e0d4515b3Tropical medicineMalariaMedical sciencesVaccinologyEnglishOxford University Research Archive - ValetPublic Library of Science2008Todryk, SBejon, PMwangi, TPlebanski, MUrban, BMarsh, KHill, AFlanagan, KBackground: Immunity to malaria develops naturally in endemic regions, but the protective immune mechanisms are poorly understood. Many vaccination strategies aim to induce T cells against divers pre-erythrocytic antigens, but correlates of protection in the field have been limited. The objective of this study was to investigate cell-mediated immune correlates of protection in natural malaria. Memory T cells reactive against thrombospondin-related adhesive protein (TRAP) and circumsporozoite (CS) protein, major vaccine candidate antigens, were measured, as were frequencies of CD4^+ CD25^high T cells, which may suppress immunity, and CD56^+ NK cells and γδ T cells, which may be effectors or may modulate immunity. Methodology and Principal Findings: 112 healthy volunteers living in rural Kenya were entered in the study. Memory T cells reactive against TRAP and CS were measured using a cultured IFNγ ELISPOT appproach, whilst CD4^+ CD25^high T cells were established early in life (<5 years) in contrast to CS, and cultured ELISPOT memory T cell responses did not correlate with ex-vivo IFNγ ELISPOT effector responses. Data was examined for associations with risk of clinical malaria for a period of 300 days. Multivariate logistic analysis incorporating age and CS response showed that cultured memory T cell responses against TRAP were associated with a significantly reduced incidence of malaria (p=0.028). This was not seen for CS responses. Higher numbers of CD4^+ CD25^high T cells, potentially regulatory T cells, were associated with a significantly increased risk of clinical malaria (p=0.039). Conclusions: These data demonstrate a role for central memory T cells in natural malaria immunity and support current vaccination strategies aimed at inducing durable protective T cell responses against the TRAP antigen. They also suggest that CD4^+ CD25^high T cells may negatively affect naturally acquired malarial immunity. |
| spellingShingle | Tropical medicine Malaria Medical sciences Vaccinology Todryk, S Bejon, P Mwangi, T Plebanski, M Urban, B Marsh, K Hill, A Flanagan, K Correlation of memory T cell responses against TRAP with protection from clinical malaria, and CD4^+ CD25 ^high T cells with susceptibility in Kenyans |
| title | Correlation of memory T cell responses against TRAP with protection from clinical malaria, and CD4^+ CD25 ^high T cells with susceptibility in Kenyans |
| title_full | Correlation of memory T cell responses against TRAP with protection from clinical malaria, and CD4^+ CD25 ^high T cells with susceptibility in Kenyans |
| title_fullStr | Correlation of memory T cell responses against TRAP with protection from clinical malaria, and CD4^+ CD25 ^high T cells with susceptibility in Kenyans |
| title_full_unstemmed | Correlation of memory T cell responses against TRAP with protection from clinical malaria, and CD4^+ CD25 ^high T cells with susceptibility in Kenyans |
| title_short | Correlation of memory T cell responses against TRAP with protection from clinical malaria, and CD4^+ CD25 ^high T cells with susceptibility in Kenyans |
| title_sort | correlation of memory t cell responses against trap with protection from clinical malaria and cd4 cd25 high t cells with susceptibility in kenyans |
| topic | Tropical medicine Malaria Medical sciences Vaccinology |
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