Safety of the malaria vaccine candidate, RTS,S/AS01E in 5 to 17 month old Kenyan and Tanzanian Children.
The malaria vaccine candidate, RTS,S/AS01(E), showed promising protective efficacy in a trial of Kenyan and Tanzanian children aged 5 to 17 months. Here we report on the vaccine's safety and tolerability. The experimental design was a Phase 2b, two-centre, double-blind (observer- and participant-blind), randomised (1∶1 ratio) controlled trial. Three doses of study or control (rabies) vaccines were administered intramuscularly at 1 month intervals. Solicited adverse events (AEs) were collected for 7 days after each vaccination. There was surveillance and reporting for unsolicited adverse events for 30 days after each vaccination. Serious adverse events (SAEs) were recorded throughout the study period which lasted for 14 months after dose 1 in Korogwe, Tanzania and an average of 18 months post-dose 1 in Kilifi, Kenya. Blood samples for safety monitoring of haematological, renal and hepatic functions were taken at baseline, 3, 10 and 14 months after dose 1. A total of 894 children received RTS,S/AS01(E) or rabies vaccine between March and August 2007. Overall, children vaccinated with RTS,S/AS01(E) had fewer SAEs (51/447) than children in the control group (88/447). One SAE episode in a RTS,S/AS01(E) recipient and nine episodes among eight rabies vaccine recipients met the criteria for severe malaria. Unsolicited AEs were reported in 78% of subjects in the RTS,S/AS01(E) group and 74% of subjects in the rabies vaccine group. In both vaccine groups, gastroenteritis and pneumonia were the most frequently reported unsolicited AE. Fever was the most frequently observed solicited AE and was recorded after 11% of RTS,S/AS01(E) doses compared to 31% of doses of rabies vaccine. The candidate vaccine RTS,S/AS01(E) showed an acceptable safety profile in children living in a malaria-endemic area in East Africa. More data on the safety of RTS,S/AS01(E) will become available from the Phase 3 programme.
National Institute for Medical Research, Tanga, Tanzania.
John
J
Lusingu
Ally
A
Olotu
Amanda
A
Leach
Marc
M
Lievens
Johan
J
Vekemans
Aurélie
A
Olivier
Sarah
S
Benns
Raimos
R
Olomi
Salum
S
Msham
Trudie
T
Lang
Jayne
J
Gould
Karin
K
Hallez
Yolanda
Y
Guerra
Patricia
P
Njuguna
Ken O
KO
Awuondo
Anangisye
A
Malabeja
Omar
O
Abdul
Samwel
S
Gesase
Denise
D
Dekker
Lincoln
L
Malle
Sadiki
S
Ismael
Neema
N
Mturi
Chris J
CJ
Drakeley
Barbara
B
Savarese
Tonya
T
Villafana
W Ripley
WR
Ballou
Joe
J
Cohen
Eleanor M
EM
Riley
Martha M
MM
Lemnge
Kevin
K
Marsh
Philip
P
Bejon
Lorenz
L
von Seidlein
D000410:Alanine Transaminase / Q000097:blood; D003404:Creatinine / Q000097:blood; D004311:Double-Blind Method; D005334:Fever / Q000209:etiology; D005759:Gastroenteritis / Q000209:etiology; D006801:Humans; D007223:Infant; D007630:Kenya; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D016778:Malaria, Falciparum / Q000276:immunology* / Q000517:prevention & control; D010146:Pain / Q000209:etiology; D010963:Plasmodium falciparum / Q000276:immunology*; D011014:Pneumonia / Q000209:etiology; D011819:Rabies Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D012894:Sleep Stages / Q000187:drug effects; D013636:Tanzania; D014611:Vaccination / Q000009:adverse effects / Q000379:methods*
D017780:Malaria Vaccines; C533816:RTS,S-AS01E vaccine; D011819:Rabies Vaccines; D003404:Creatinine; D000410:Alanine Transaminase