TY - JOUR
T1 - Randomized controlled trial of RTS,S/AS02D and RTS,S/AS01E malaria candidate vaccines given according to different schedules in Ghanaian children
AU - Owusu-Agyei, Seth
AU - Ansong, Daniel
AU - Asante, Kwaku
AU - Owusu, Sandra Kwarteng
AU - Owusu, Ruth
AU - Brobby, Naana Ayiwa Wireko
AU - Dosoo, David
AU - Akoto, Alex Osei
AU - Osei-Kwakye, Kingsley
AU - Adjei, Emmanuel Asafo
AU - Boahen, Kwadwo Owusu
AU - Sylverken, Justice
AU - Adjei, George
AU - Sambian, David
AU - Apanga, Stephen
AU - Kayan, Kingsley
AU - Vekemans, Johan
AU - Ofori-Anyinam, Opokua
AU - Leach, Amanda
AU - Lievens, Marc
AU - Demoitie, Marie Ange
AU - Dubois, Marie Claude
AU - Cohen, Joe
AU - Ballou, W. Ripley
AU - Savarese, Barbara
AU - Chandramohan, Daniel
AU - Gyapong, John Owusu
AU - Milligan, Paul
AU - Antwi, Sampson
AU - Agbenyega, Tsiri
AU - Greenwood, Brian
AU - Evans, Jennifer
PY - 2009
Y1 - 2009
N2 - 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/AS01E and RTS,S/AS02D in infants and young children 5-17 months of age in Ghana. Methodology: 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/AS01E or rabies vaccine at one center and RTS,S/AS01E or RTS,S/AS02D at the other. For the other schedules at both study sites, they received RTS,S/AS01E or RTS,S/AS02D. 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/AS01E 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/AS01E than RTS,S/AS02D. Both candidate vaccines were highly immunogenic for anti-circumsporozoite and anti-Hepatitis B Virus surface antigen antibodies. Recipients of RTS,S/AS01E compared to RTS,S/AS02D 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/ AS01E schedules. Conclusions: Both candidate malaria vaccines were well tolerated. Anti-circumsporozoite responses were greater with RTS,S/AS01E than RTS,S/AS02D and when 3 rather than 2 doses were given. This study supports the selection of RTS,S/AS01E and a 3 dose schedule for further development in children and infants.
AB - 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/AS01E and RTS,S/AS02D in infants and young children 5-17 months of age in Ghana. Methodology: 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/AS01E or rabies vaccine at one center and RTS,S/AS01E or RTS,S/AS02D at the other. For the other schedules at both study sites, they received RTS,S/AS01E or RTS,S/AS02D. 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/AS01E 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/AS01E than RTS,S/AS02D. Both candidate vaccines were highly immunogenic for anti-circumsporozoite and anti-Hepatitis B Virus surface antigen antibodies. Recipients of RTS,S/AS01E compared to RTS,S/AS02D 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/ AS01E schedules. Conclusions: Both candidate malaria vaccines were well tolerated. Anti-circumsporozoite responses were greater with RTS,S/AS01E than RTS,S/AS02D and when 3 rather than 2 doses were given. This study supports the selection of RTS,S/AS01E and a 3 dose schedule for further development in children and infants.
UR - http://www.scopus.com/inward/record.url?scp=70350002150&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0007302
DO - 10.1371/journal.pone.0007302
M3 - Article
C2 - 19806184
SN - 1932-6203
VL - 4
SP - 1
EP - 11
JO - PLoS One
JF - PLoS One
IS - 10
M1 - e7302
ER -