PMID- 21124768
OWN - NLM
STAT- MEDLINE
DCOM- 20110427
LR  - 20211020
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 5
IP  - 11
DP  - 2010 Nov 29
TI  - Safety of the malaria vaccine candidate, RTS,S/AS01E in 5 to 17 month old Kenyan 
      and Tanzanian Children.
PG  - e14090
LID - 10.1371/journal.pone.0014090 [doi]
LID - e14090
AB  - 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 
      (1ratio1 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.
FAU - Lusingu, John
AU  - Lusingu J
AD  - National Institute for Medical Research, Tanga, Tanzania.
FAU - Olotu, Ally
AU  - Olotu A
FAU - Leach, Amanda
AU  - Leach A
FAU - Lievens, Marc
AU  - Lievens M
FAU - Vekemans, Johan
AU  - Vekemans J
FAU - Olivier, Aurelie
AU  - Olivier A
FAU - Benns, Sarah
AU  - Benns S
FAU - Olomi, Raimos
AU  - Olomi R
FAU - Msham, Salum
AU  - Msham S
FAU - Lang, Trudie
AU  - Lang T
FAU - Gould, Jayne
AU  - Gould J
FAU - Hallez, Karin
AU  - Hallez K
FAU - Guerra, Yolanda
AU  - Guerra Y
FAU - Njuguna, Patricia
AU  - Njuguna P
FAU - Awuondo, Ken O
AU  - Awuondo KO
FAU - Malabeja, Anangisye
AU  - Malabeja A
FAU - Abdul, Omar
AU  - Abdul O
FAU - Gesase, Samwel
AU  - Gesase S
FAU - Dekker, Denise
AU  - Dekker D
FAU - Malle, Lincoln
AU  - Malle L
FAU - Ismael, Sadiki
AU  - Ismael S
FAU - Mturi, Neema
AU  - Mturi N
FAU - Drakeley, Chris J
AU  - Drakeley CJ
FAU - Savarese, Barbara
AU  - Savarese B
FAU - Villafana, Tonya
AU  - Villafana T
FAU - Ballou, W Ripley
AU  - Ballou WR
FAU - Cohen, Joe
AU  - Cohen J
FAU - Riley, Eleanor M
AU  - Riley EM
FAU - Lemnge, Martha M
AU  - Lemnge MM
FAU - Marsh, Kevin
AU  - Marsh K
FAU - Bejon, Philip
AU  - Bejon P
FAU - von Seidlein, Lorenz
AU  - von Seidlein L
LA  - eng
SI  - ClinicalTrials.gov/NCT00380393
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20101129
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Malaria Vaccines)
RN  - 0 (RTS,S-AS01E vaccine)
RN  - 0 (Rabies Vaccines)
RN  - AYI8EX34EU (Creatinine)
RN  - EC 2.6.1.2 (Alanine Transaminase)
SB  - IM
EIN - PLoS One. 2010; 5(12) doi: 
      10.1371/annotation/3b62fdef-4cdd-40cc-b69d-69afd2000c4f
EIN - PLoS One. 2010;5(12) doi: 10.1371/annotation/0543a689-83a6-4528-92a1-a0f978b47fcb
MH  - Alanine Transaminase/blood
MH  - Creatinine/blood
MH  - Double-Blind Method
MH  - Fever/etiology
MH  - Gastroenteritis/etiology
MH  - Humans
MH  - Infant
MH  - Kenya
MH  - Malaria Vaccines/administration & dosage/adverse effects/*immunology
MH  - Malaria, Falciparum/*immunology/prevention & control
MH  - Pain/etiology
MH  - Plasmodium falciparum/*immunology
MH  - Pneumonia/etiology
MH  - Rabies Vaccines/administration & dosage/adverse effects/immunology
MH  - Sleep Stages/drug effects
MH  - Tanzania
MH  - Vaccination/adverse effects/*methods
PMC - PMC2993932
COIS- Competing Interests: AL, ML, JV, AO, KH, YG, WRB and JC are employed by GSK 
      Biologicals. AL, SB, JG, WRB and JC own shares in GSK. WRB and JC are listed as 
      inventors of patented malaria vaccines. BS is and TV was employed by MVI, which 
      supports the development and testing of several malaria vaccines. TV was formerly 
      at PATH, MVI, and is currently at MedImmune, which develops, manufactures and 
      markets formulations for use in immunization programs. The authors are not aware 
      of any other potential conflict of interest relevant to this article. This does 
      not alter the authors' adherence to all the PLoS ONE policies on sharing data and 
      materials.
EDAT- 2010/12/03 06:00
MHDA- 2011/04/28 06:00
PMCR- 2010/11/29
CRDT- 2010/12/03 06:00
PHST- 2010/07/19 00:00 [received]
PHST- 2010/10/28 00:00 [accepted]
PHST- 2010/12/03 06:00 [entrez]
PHST- 2010/12/03 06:00 [pubmed]
PHST- 2011/04/28 06:00 [medline]
PHST- 2010/11/29 00:00 [pmc-release]
AID - 10-PONE-RA-21299R2 [pii]
AID - 10.1371/journal.pone.0014090 [doi]
PST - epublish
SO  - PLoS One. 2010 Nov 29;5(11):e14090. doi: 10.1371/journal.pone.0014090.