T Cell Responses to the RTS,S/AS01E and RTS,S/AS02D Malaria Candidate Vaccines Administered According to Different Schedules to Ghanaian Children
Background The Plasmodium falciparum pre-erythrocytic stage candidate vaccine RTS,S is being developed for protection of young children against malaria in sub-Saharan Africa. RTS,S formulated with the liposome based adjuvant AS01E or the oil-in-water based adjuvant AS02D induces P. falciparum circum...
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Published in | PloS one Vol. 6; no. 4; p. e18891 |
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Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
San Francisco
Public Library of Science
27.04.2011
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Subjects | |
Online Access | Get full text |
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Summary: | Background The Plasmodium falciparum pre-erythrocytic stage candidate vaccine RTS,S is being developed for protection of young children against malaria in sub-Saharan Africa. RTS,S formulated with the liposome based adjuvant AS01E or the oil-in-water based adjuvant AS02D induces P. falciparum circumsporozoite (CSP) antigen-specific antibody and T cell responses which have been associated with protection in the experimental malaria challenge model in adults. Methods This study was designed to evaluate the safety and immunogenicity induced over a 19 month period by three vaccination schedules (0,1-, 0,1,2- and 0,1,7-month) of RTS,S/AS01E and RTS,S/AS02D in children aged 5–17 months in two research centers in Ghana. Control Rabies vaccine using the 0,1,2-month schedule was used in one of two study sites. Results Whole blood antigen stimulation followed by intra-cellular cytokine staining showed RTS,S/AS01E induced CSP specific CD4 T cells producing IL-2, TNF-α, and IFN-γ. Higher T cell responses were induced by a 0,1,7-month immunization schedule as compared with a 0,1- or 0,1,2-month schedule. RTS,S/AS01E induced higher CD4 T cell responses as compared to RTS,S/AS02D when given on a 0,1,7-month schedule. Conclusions These findings support further Phase III evaluation of RTS,S/AS01E. The role of immune effectors and immunization schedules on vaccine protection are currently under evaluation. Trial Registration ClinicalTrials.gov NCT00360230 |
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Bibliography: | Conceived and designed the experiments: DA KPA JV PD BMS JC BMG JAE TA PJM SO-A. Performed the experiments: DA KPA SKO RO NAWB DD AO-A KO-K EA-A KOB JS GA DS SA KK MHJ SA JAE TA PJM SO-A. Analyzed the data: DA KPA JV MJJL EJ PD JC BMG JAE TA PJM SO-A. Contributed reagents/materials/analysis tools: MHJ MJJL ACO EJ BMS PJM. Wrote the paper: DA KPA JV MJJL ACO PD BMG PJM. |
ISSN: | 1932-6203 1932-6203 |
DOI: | 10.1371/journal.pone.0018891 |