• Seth Owusu-Agyei, Daniel Ansong, Kwaku Asante, Sandra Kwarteng Owusu, Ruth Owusu, Naana Ayiwa Wireko Brobby, David Dosoo, Alex Osei Akoto, Kingsley Osei-Kwakye, Emmanuel Asafo Adjei, Kwadwo Owusu Boahen, Justice Sylverken, George Adjei, David Sambian, Stephen Apanga, Kingsley Kayan, Johan Vekemans, Opokua Ofori-Anyinam, Amanda Leach, Marc Lievens, Marie-Ange Demoitie, Marie-Claude Dubois, Joe Cohen, W Ripley Ballou, Barbara Savarese, Daniel Chandramohan, John Owusu Gyapong, Paul Milligan, Sampson Antwi, Tsiri Agbenyega, Brian Greenwood, and Jennifer Evans.
• Kintampo Health Research Centre, Health Research Unit, Kintampo, Ghana. Seth.owusu-agyei@ghana-khrc.org
• Plos One. 2009 Jan 1;4(10):e7302.

BackgroundThe 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.MethodologyA 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.ResultsThe 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.ConclusionsBoth 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.Trial RegistrationClinicalTrials.gov NCT00360230.

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