T Cell Responses to the RTS,S/AS01(E) and RTS,S/AS02(D) Malaria Candidate Vaccines Administered According to Different Schedules to Ghanaian Children


Ansong, D; Asante, KP; Vekemans, J; Owusu, SK; Owusu, R; Brobby, NA; Dosoo, D; Osei-Akoto, A; Osei-Kwakye, K; Asafo-Adjei, E; Boahen, KO; Sylverken, J; Adjei, G; Sambian, D; Apanga, S; Kayan, K; Janssens, MH; Lievens, MJ; Olivier, AC; Jongert, E; Dubois, P; Savarese, BM; Cohen, J; Antwi, S; Greenwood, BM; Evans, JA; Agbenyega, T; Moris, PJ; Owusu-Agyei, S; (2011) T Cell Responses to the RTS,S/AS01(E) and RTS,S/AS02(D) Malaria Candidate Vaccines Administered According to Different Schedules to Ghanaian Children. PLoS One, 6 (4). e18891. ISSN 1932-6203 DOI: 10.1371/journal.pone.0018891

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Abstract

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 AS01(E) or the oil-in-water based adjuvant AS02(D) 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.<br/> 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/AS01(E) and RTS,S/AS02(D) 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.<br/> RESULTS: Whole blood antigen stimulation followed by intra-cellular cytokine staining showed RTS,S/AS01(E) 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/AS01(E) induced higher CD4 T cell responses as compared to RTS,S/AS02(D) when given on a 0,1,7-month schedule.<br/> CONCLUSIONS: These findings support further Phase III evaluation of RTS,S/AS01(E). The role of immune effectors and immunization schedules on vaccine protection are currently under evaluation.<br/> TRIAL REGISTRATION: ClinicalTrials.gov NCT00360230.<br/>

Item Type: Article
Keywords: FALCIPARUM CIRCUMSPOROZOITE-PROTEIN, RANDOMIZED CONTROLLED-TRIAL, IMMUNE ADULT MEN, DOUBLE-BLIND, LIVER STAGES, B-CELL, SAFETY, IMMUNOGENICITY, EFFICACY, ANTIGEN
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Disease Control
Research Centre: Malaria Centre
Centre for Maternal, Reproductive and Child Health (MARCH)
Vaccine Centre
PubMed ID: 21556142
Web of Science ID: 290019400012
URI: http://researchonline.lshtm.ac.uk/id/eprint/717

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