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",
    year = "2009",
    doi = "10.1371/journal.pone.0007302",
    language = "English",
    volume = "4",
    pages = "1--11",
    journal = "PLoS One",
    issn = "1932-6203",
    publisher = "Public Library of Science (PLoS)",
    number = "10",

    }

    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 -