title: Randomized controlled trial of RTS,S/AS02D and RTS,S/AS01E malaria candidate vaccines given according to different schedules in Ghanaian children.
abstract: BACKGROUND
  The target delivery channel of RTS,S candidate malaria vaccines in malaria-endemic countries in Africa is the World Health Organisation Expanded Program on Immunization. As an Adjuvant System, age de-escalation and schedule selection step, this study assessed 3 schedules of RTS,S/AS01(E) and RTS,S/AS02(D) in infants and young children 5-17 months of age in Ghana.
  
  
  METHODS
  A Phase II, partially-blind randomized controlled study (blind to vaccine, not to schedule), of 19 months duration was conducted in two (2) centres in Ghana between August 2006 and May 2008. Subjects were allocated randomly (1:1:1:1:1:1) to one of six study groups at each study site, each defining which vaccine should be given and by which schedule (0,1-, 0,1,2- or 0,1,7-months). For the 0,1,2-month schedule participants received RTS,S/AS01(E) or rabies vaccine at one center and RTS,S/AS01(E) or RTS,S/AS02(D) at the other. For the other schedules at both study sites, they received RTS,S/AS01(E) or RTS,S/AS02(D). The primary outcome measure was the occurrence of serious adverse events until 10 months post dose 1.
  
  
  RESULTS
  The number of serious adverse events reported across groups was balanced. One child had a simple febrile convulsion, which evolved favourably without sequelae, considered to be related to RTS,S/AS01(E) vaccination. Low grade reactions occurred slightly more frequently in recipients of RTS,S/AS than rabies vaccines; grade 3 reactions were infrequent. Less local reactogenicity occurred with RTS,S/AS01(E) than RTS,S/AS02(D). Both candidate vaccines were highly immunogenic for anti-circumsporozoite and anti-Hepatitis B Virus surface antigen antibodies. Recipients of RTS,S/AS01(E) compared to RTS,S/AS02(D) had higher peak anti-circumsporozoite antibody responses for all 3 schedules. Three dose schedules were more immunogenic than 2 dose schedules. Area under the curve analyses for anti-circumsporozoite antibodies were comparable between the 0,1,2- and 0,1,7-month RTS,S/AS01(E) schedules.
  
  
  CONCLUSIONS
  Both candidate malaria vaccines were well tolerated. Anti-circumsporozoite responses were greater with RTS,S/AS01(E) than RTS,S/AS02(D) and when 3 rather than 2 doses were given. This study supports the selection of RTS,S/AS01(E) and a 3 dose schedule for further development in children and infants.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00360230.
authors.affiliation: Kintampo Health Research Centre, Health Research Unit, Kintampo, Ghana. Seth.owusu-agyei@ghana-khrc.org
authors.forename: Seth
authors.initials: S
authors.lastname: Owusu-Agyei
authors.forename: Daniel
authors.initials: D
authors.lastname: Ansong
authors.forename: Kwaku
authors.initials: K
authors.lastname: Asante
authors.forename: Sandra
authors.initials: S
authors.lastname: Kwarteng Owusu
authors.forename: Ruth
authors.initials: R
authors.lastname: Owusu
authors.forename: Naana Ayiwa
authors.initials: NA
authors.lastname: Wireko 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 Asafo
authors.initials: EA
authors.lastname: Adjei
authors.forename: Kwadwo Owusu
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: Johan
authors.initials: J
authors.lastname: Vekemans
authors.forename: Opokua
authors.initials: O
authors.lastname: Ofori-Anyinam
authors.forename: Amanda
authors.initials: A
authors.lastname: Leach
authors.forename: Marc
authors.initials: M
authors.lastname: Lievens
authors.forename: Marie-Ange
authors.initials: MA
authors.lastname: Demoitie
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Dubois
authors.forename: Joe
authors.initials: J
authors.lastname: Cohen
authors.forename: W Ripley
authors.initials: WR
authors.lastname: Ballou
authors.forename: Barbara
authors.initials: B
authors.lastname: Savarese
authors.forename: Daniel
authors.initials: D
authors.lastname: Chandramohan
authors.forename: John Owusu
authors.initials: JO
authors.lastname: Gyapong
authors.forename: Paul
authors.initials: P
authors.lastname: Milligan
authors.forename: Sampson
authors.initials: S
authors.lastname: Antwi
authors.forename: Tsiri
authors.initials: T
authors.lastname: Agbenyega
authors.forename: Brian
authors.initials: B
authors.lastname: Greenwood
authors.forename: Jennifer
authors.initials: J
authors.lastname: Evans
mesh_terms: D000818:Animals; D019540:Area Under Curve; D002648:Child; D004334:Drug Administration Schedule; D005260:Female; D005869:Ghana; D006801:Humans; D007223:Infant; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000627:therapeutic use*; D016778:Malaria, Falciparum / Q000517:prevention & control*; D008297:Male; D010963:Plasmodium falciparum / Q000276:immunology; D013997:Time Factors; D016896:Treatment Outcome; D014611:Vaccination
chemical_list: D017780:Malaria Vaccines; C533816:RTS,S-AS01E vaccine; C533817:RTS,S-AS02D vaccine