Safety of the malaria vaccine candidate, RTS,S/AS01E in 5 to 17 month old Kenyan and Tanzanian Children.

Abstract

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.

• Authors: John Lusingu, Ally Olotu, Amanda Leach, Marc Lievens, Johan Vekemans, Aurélie Olivier, Sarah Benns, Raimos Olomi, Salum Msham, Trudie Lang, Jayne Gould, Karin Hallez, Yolanda Guerra, Patricia Njuguna, Ken O Awuondo, Anangisye Malabeja, Omar Abdul, Samwel Gesase, Denise Dekker, Lincoln Malle, Sadiki Ismael, Neema Mturi, Chris J Drakeley, Barbara Savarese, Tonya Villafana, W Ripley Ballou, Joe Cohen, Eleanor M Riley, Martha M Lemnge, Kevin Marsh, Philip Bejon, Lorenz von Seidlein
• Journal: PloS one (PLoS One) Vol. 5 Issue 11 Pg. e14090 (Nov 29 2010) ISSN: 1932-6203 [Electronic] United States
• PMID: 21124768 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Malaria Vaccines
• RTS,S-AS01E vaccine
• Rabies Vaccines
• Creatinine
• Alanine Transaminase

Topics

• Alanine Transaminase (blood)
• Creatinine (blood)
• Double-Blind Method
• Fever (etiology)
• Gastroenteritis (etiology)
• Humans
• Infant
• Kenya
• Malaria Vaccines (administration & dosage, adverse effects, immunology)
• Malaria, Falciparum (immunology, prevention & control)
• Pain (etiology)
• Plasmodium falciparum (immunology)
• Pneumonia (etiology)
• Rabies Vaccines (administration & dosage, adverse effects, immunology)
• Sleep Stages (drug effects)
• Tanzania
• Vaccination (adverse effects, methods)