TY - JOUR
T1 - Safety and efficacy of the RTS,S/AS01E candidate malaria vaccine given with expanded-programme-on-immunisation vaccines
T2 - 19 month follow-up of a randomised, open-label, phase 2 trial
AU - Asante, Kwaku Poku
AU - Abdulla, Salim
AU - Agnandji, Selidji
AU - Lyimo, John
AU - Vekemans, Johan
AU - Soulanoudjingar, Solange
AU - Owusu, Ruth
AU - Shomari, Mwanajaa
AU - Leach, Amanda
AU - Jongert, Erik
AU - Salim, Nahya
AU - Fernandes, Jose F.
AU - Dosoo, David
AU - Chikawe, Maria
AU - Issifou, Saadou
AU - Osei-Kwakye, Kingsley
AU - Lievens, Marc
AU - Paricek, Maria
AU - Möller, Tina
AU - Apanga, Stephen
AU - Mwangoka, Grace
AU - Dubois, Marie Claude
AU - Madi, Tigani
AU - Kwara, Evans
AU - Minja, Rose
AU - Hounkpatin, Aurore B.
AU - Boahen, Owusu
AU - Kayan, Kingsley
AU - Adjei, George
AU - Chandramohan, Daniel
AU - Carter, Terrell
AU - Vansadia, Preeti
AU - Sillman, Marla
AU - Savarese, Barbara
AU - Loucq, Christian
AU - Lapierre, Didier
AU - Greenwood, Brian
AU - Cohen, Joe
AU - Kremsner, Peter
AU - Owusu-Agyei, Seth
AU - Tanner, Marcel
AU - Lell, Bertrand
PY - 2011/10
Y1 - 2011/10
N2 - Background: RTS,S/AS01E is the lead candidate malaria
vaccine. We recently showed efficacy against clinical falciparum malaria in
5–17 month old children, during an average of 8 months follow-up. We aimed to
assess the efficacy of RTS,S/AS01E during 15 months of follow-up.Methods: Between March, 2007, and October, 2008, we
enrolled healthy children aged 5–17 months in Kilifi, Kenya, and Korogwe,
Tanzania. Computer-generated block randomisation was used to randomly assign
participants (1:1) to receive three doses (at month 0, 1, and 2) of either
RTS,S/AS01E or human diploid-cell rabies vaccine. The primary endpoint was time
to first clinical malaria episode, defined as the presence of fever
(temperature ≥37·5°C) and a Plasmodium falciparum density of 2500/μL
or more. Follow-up was 12 months for children from Korogwe and 15 months for
children from Kilifi. Primary analysis was per protocol. In a post-hoc
modelling analysis we characterised the associations between
anti-circumsporozoite antibodies and protection against clinical malaria episodes.
This study is registered with ClinicalTrials.gov, number NCT00380393.Findings: 894 children were assigned, 447 in each
treatment group. In the per-protocol analysis, 82 of 415 children in the
RTS,S/AS01E group and 125 of 420 in the rabies vaccine group had first or only
clinical malaria episode by 12 months, vaccine efficacy 39·2% (95% CI
19·5–54·1, p=0·0005). At 15 months follow-up, 58 of 209 children in the
RTS,S/AS01E group and 85 of 206 in the rabies vaccine group had first or only
clinical malaria episode, vaccine efficacy 45·8% (24·1–61·3, p=0·0004). At 12
months after the third dose, anti-circumsporozoite antibody titre data were
available for 390 children in the RTS,S/AS01E group and 391 in the rabies
group. A mean of 15 months (range 12–18 months) data were available for 172
children in the RTS,S/AS01E group and 155 in the rabies group. These titres at
1 month after the third dose were not associated with protection, but titres at
6·5 months were. The level of protection increased abruptly over a narrow range
of antibody concentrations. The most common adverse events were pneumonia,
febrile convulsion, gastroenteritis, and P falciparum malaria.Interpretation: RTS,S/AS01E confers sustained efficacy for
at least 15 months and shows promise as a potential public health intervention
against childhood malaria in malaria endemic countries.
AB - Background: RTS,S/AS01E is the lead candidate malaria
vaccine. We recently showed efficacy against clinical falciparum malaria in
5–17 month old children, during an average of 8 months follow-up. We aimed to
assess the efficacy of RTS,S/AS01E during 15 months of follow-up.Methods: Between March, 2007, and October, 2008, we
enrolled healthy children aged 5–17 months in Kilifi, Kenya, and Korogwe,
Tanzania. Computer-generated block randomisation was used to randomly assign
participants (1:1) to receive three doses (at month 0, 1, and 2) of either
RTS,S/AS01E or human diploid-cell rabies vaccine. The primary endpoint was time
to first clinical malaria episode, defined as the presence of fever
(temperature ≥37·5°C) and a Plasmodium falciparum density of 2500/μL
or more. Follow-up was 12 months for children from Korogwe and 15 months for
children from Kilifi. Primary analysis was per protocol. In a post-hoc
modelling analysis we characterised the associations between
anti-circumsporozoite antibodies and protection against clinical malaria episodes.
This study is registered with ClinicalTrials.gov, number NCT00380393.Findings: 894 children were assigned, 447 in each
treatment group. In the per-protocol analysis, 82 of 415 children in the
RTS,S/AS01E group and 125 of 420 in the rabies vaccine group had first or only
clinical malaria episode by 12 months, vaccine efficacy 39·2% (95% CI
19·5–54·1, p=0·0005). At 15 months follow-up, 58 of 209 children in the
RTS,S/AS01E group and 85 of 206 in the rabies vaccine group had first or only
clinical malaria episode, vaccine efficacy 45·8% (24·1–61·3, p=0·0004). At 12
months after the third dose, anti-circumsporozoite antibody titre data were
available for 390 children in the RTS,S/AS01E group and 391 in the rabies
group. A mean of 15 months (range 12–18 months) data were available for 172
children in the RTS,S/AS01E group and 155 in the rabies group. These titres at
1 month after the third dose were not associated with protection, but titres at
6·5 months were. The level of protection increased abruptly over a narrow range
of antibody concentrations. The most common adverse events were pneumonia,
febrile convulsion, gastroenteritis, and P falciparum malaria.Interpretation: RTS,S/AS01E confers sustained efficacy for
at least 15 months and shows promise as a potential public health intervention
against childhood malaria in malaria endemic countries.
UR - http://www.scopus.com/inward/record.url?scp=80053236891&partnerID=8YFLogxK
U2 - 10.1016/S1473-3099(11)70100-1
DO - 10.1016/S1473-3099(11)70100-1
M3 - Article
C2 - 21782519
VL - 11
SP - 741
EP - 749
JO - The Lancet Infectious Diseases
JF - The Lancet Infectious Diseases
SN - 1473-3099
IS - 10
ER -