Randomized controlled trial of RTS,S/AS02D and RTS,S/AS01E malaria candidate vaccines given according to different schedules in Ghanaian children

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 & 12 others 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, Jennifer Evans

Research output: Contribution to journalArticleResearchpeer-review

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.

Original languageEnglish
Article numbere7302
Pages (from-to)1-11
Number of pages11
JournalPLoS One
Volume4
Issue number10
DOIs
Publication statusPublished - 2009

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Malaria Vaccines
Rabies Vaccines
Appointments and Schedules
Vaccines
Randomized Controlled Trials
vaccines
Antibodies
dosage
Immunization
Ghana
rabies
antibodies
Surface Antigens
Viruses
infant development
child development
Health
Hepatitis B virus
complications (disease)
surface antigens

Cite this

Owusu-Agyei, S., Ansong, D., Asante, K., Owusu, S. K., Owusu, R., Brobby, N. A. W., ... Evans, J. (2009). Randomized controlled trial of RTS,S/AS02D and RTS,S/AS01E malaria candidate vaccines given according to different schedules in Ghanaian children. PLoS One, 4(10), 1-11. [e7302]. https://doi.org/10.1371/journal.pone.0007302
Owusu-Agyei, Seth ; Ansong, Daniel ; Asante, Kwaku ; Owusu, Sandra Kwarteng ; Owusu, Ruth ; Brobby, Naana Ayiwa Wireko ; Dosoo, David ; Akoto, Alex Osei ; Osei-Kwakye, Kingsley ; Adjei, Emmanuel Asafo ; Boahen, Kwadwo Owusu ; Sylverken, Justice ; Adjei, George ; Sambian, David ; Apanga, Stephen ; Kayan, Kingsley ; Vekemans, Johan ; Ofori-Anyinam, Opokua ; Leach, Amanda ; Lievens, Marc ; Demoitie, Marie Ange ; Dubois, Marie Claude ; Cohen, Joe ; Ballou, W. Ripley ; Savarese, Barbara ; Chandramohan, Daniel ; Gyapong, John Owusu ; Milligan, Paul ; Antwi, Sampson ; Agbenyega, Tsiri ; Greenwood, Brian ; Evans, Jennifer. / Randomized controlled trial of RTS,S/AS02D and RTS,S/AS01E malaria candidate vaccines given according to different schedules in Ghanaian children. In: PLoS One. 2009 ; Vol. 4, No. 10. pp. 1-11.
@article{5b8f509380054392b88602dc97a44a70,
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/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.",
author = "Seth Owusu-Agyei and Daniel Ansong and Kwaku Asante and Owusu, {Sandra Kwarteng} and Ruth Owusu and Brobby, {Naana Ayiwa Wireko} and David Dosoo and Akoto, {Alex Osei} and Kingsley Osei-Kwakye and Adjei, {Emmanuel Asafo} and Boahen, {Kwadwo Owusu} and Justice Sylverken and George Adjei and David Sambian and Stephen Apanga and Kingsley Kayan and Johan Vekemans and Opokua Ofori-Anyinam and Amanda Leach and Marc Lievens and Demoitie, {Marie Ange} and Dubois, {Marie Claude} and Joe Cohen and Ballou, {W. Ripley} and Barbara Savarese and Daniel Chandramohan and Gyapong, {John Owusu} and Paul Milligan and Sampson Antwi and Tsiri Agbenyega and Brian Greenwood and Jennifer Evans",
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Owusu-Agyei, S, Ansong, D, Asante, K, Owusu, SK, Owusu, R, Brobby, NAW, Dosoo, D, Akoto, AO, Osei-Kwakye, K, Adjei, EA, Boahen, KO, Sylverken, J, Adjei, G, Sambian, D, Apanga, S, Kayan, K, Vekemans, J, Ofori-Anyinam, O, Leach, A, Lievens, M, Demoitie, MA, Dubois, MC, Cohen, J, Ballou, WR, Savarese, B, Chandramohan, D, Gyapong, JO, Milligan, P, Antwi, S, Agbenyega, T, Greenwood, B & Evans, J 2009, 'Randomized controlled trial of RTS,S/AS02D and RTS,S/AS01E malaria candidate vaccines given according to different schedules in Ghanaian children', PLoS One, vol. 4, no. 10, e7302, pp. 1-11. https://doi.org/10.1371/journal.pone.0007302

Randomized controlled trial of RTS,S/AS02D and RTS,S/AS01E malaria candidate vaccines given according to different schedules in Ghanaian children. / Owusu-Agyei, Seth; Ansong, Daniel; Asante, Kwaku; Owusu, Sandra Kwarteng; Owusu, Ruth; Brobby, Naana Ayiwa Wireko; Dosoo, David; Akoto, Alex Osei; Osei-Kwakye, Kingsley; Adjei, Emmanuel Asafo; Boahen, Kwadwo Owusu; Sylverken, Justice; Adjei, George; Sambian, David; Apanga, Stephen; Kayan, Kingsley; Vekemans, Johan; Ofori-Anyinam, Opokua; Leach, Amanda; Lievens, Marc; Demoitie, Marie Ange; Dubois, Marie Claude; Cohen, Joe; Ballou, W. Ripley; Savarese, Barbara; Chandramohan, Daniel; Gyapong, John Owusu; Milligan, Paul; Antwi, Sampson; Agbenyega, Tsiri; Greenwood, Brian; Evans, Jennifer.

In: PLoS One, Vol. 4, No. 10, e7302, 2009, p. 1-11.

Research output: Contribution to journalArticleResearchpeer-review

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

VL - 4

SP - 1

EP - 11

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 10

M1 - e7302

ER -