title: 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.
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.
  
  
  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.
  
  
  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.
  
  
  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.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00360230.
authors.affiliation: School of Medical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana. ansongd@yahoo.com
authors.forename: Daniel
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authors.lastname: Ansong
authors.forename: Kwaku P
authors.initials: KP
authors.lastname: Asante
authors.forename: Johan
authors.initials: J
authors.lastname: Vekemans
authors.forename: Sandra K
authors.initials: SK
authors.lastname: Owusu
authors.forename: Ruth
authors.initials: R
authors.lastname: Owusu
authors.forename: Naana A W
authors.initials: NA
authors.lastname: Brobby
authors.forename: David
authors.initials: D
authors.lastname: Dosoo
authors.forename: Alex
authors.initials: A
authors.lastname: Osei-Akoto
authors.forename: Kingsley
authors.initials: K
authors.lastname: Osei-Kwakye
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Asafo-Adjei
authors.forename: Kwadwo O
authors.initials: KO
authors.lastname: Boahen
authors.forename: Justice
authors.initials: J
authors.lastname: Sylverken
authors.forename: George
authors.initials: G
authors.lastname: Adjei
authors.forename: David
authors.initials: D
authors.lastname: Sambian
authors.forename: Stephen
authors.initials: S
authors.lastname: Apanga
authors.forename: Kingsley
authors.initials: K
authors.lastname: Kayan
authors.forename: Michel H
authors.initials: MH
authors.lastname: Janssens
authors.forename: Marc J J
authors.initials: MJ
authors.lastname: Lievens
authors.forename: Aurelie C
authors.initials: AC
authors.lastname: Olivier
authors.forename: Erik
authors.initials: E
authors.lastname: Jongert
authors.forename: Patrice
authors.initials: P
authors.lastname: Dubois
authors.forename: Barbara M
authors.initials: BM
authors.lastname: Savarese
authors.forename: Joe
authors.initials: J
authors.lastname: Cohen
authors.forename: Sampson
authors.initials: S
authors.lastname: Antwi
authors.forename: Brian M
authors.initials: BM
authors.lastname: Greenwood
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Evans
authors.forename: Tsiri
authors.initials: T
authors.lastname: Agbenyega
authors.forename: Philippe J
authors.initials: PJ
authors.lastname: Moris
authors.forename: Seth
authors.initials: S
authors.lastname: Owusu-Agyei
mesh_terms: D000913:Antibodies, Protozoan / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000378:metabolism; D005434:Flow Cytometry; D005869:Ghana; D006801:Humans; D007223:Infant; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000913:Antibodies, Protozoan; D016207:Cytokines; D017780:Malaria Vaccines