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© 2009 Owusu-Agyei et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

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/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.

Trial Registration

ClinicalTrials.gov NCT00360230

Details

Title
Randomized Controlled Trial of RTS,S/AS02D and RTS,S/AS01E Malaria Candidate Vaccines Given According to Different Schedules in Ghanaian Children
Author
Owusu-Agyei, Seth; Ansong, Daniel; Asante, Kwaku; Sandra Kwarteng Owusu; Owusu, Ruth; Naana Ayiwa Wireko Brobby; Dosoo, David; Alex Osei Akoto; Osei-Kwakye, Kingsley; Adjei, Emmanuel Asafo; Kwadwo Owusu Boahen; Justice Sylverken; Adjei, George; Sambian, David; Apanga, Stephen; Kingsley Kayan; Vekemans, Johan; Ofori-Anyinam, Opokua; Leach, Amanda; Lievens, Marc; Marie-Ange Demoitie; Dubois, Marie-Claude; Cohen, Joe; W Ripley Ballou; Savarese, Barbara; Chandramohan, Daniel; John Owusu Gyapong; Milligan, Paul; Sampson Antwi; Tsiri Agbenyega; Greenwood, Brian; Evans, Jennifer
First page
e7302
Section
Research Article
Publication year
2009
Publication date
Oct 2009
Publisher
Public Library of Science
e-ISSN
19326203
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
1292305267
Copyright
© 2009 Owusu-Agyei et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.