Results published in the New England Journal of Medicine revealed that the world’s most clinically advanced malaria vaccine candidate provides both infants and young children with significant protection against malaria. Two separate phase II trials reaffirmed earlier study results and support the ongoing efforts, pending regulatory approvals, to launch the phase III study of GlaxoSmithKline (GSK) Biologicals’ RTS,S/AS vaccine candidate across Africa (Abdulla et al. 2008, Bejon et al. 2008). The vaccine RTS,S was invented, developed and manufactured in laboratories at GSK Biologicals’ headquarters in Belgium in the late 1980s and initially tested in US volunteers as part of a collaboration with the US Walter Reed Army Institute of Research.

In infants, data show for the first time that the vaccine candidate can be administered as part of existing African national immunization programs. In children aged 5 to 17 months, the candidate RTS,S/AS01 reduced the risk of clinical episodes of malaria by 53 percent over an eight-month follow-up period and was shown to have a promising safety profile. The studies were conducted in Kenya and Tanzania and were presented as highlights at the American Society for Tropical Medicine and Hygiene (ASTMH) annual meeting in New Orleans at the day they were also published by the New England Journal of Medicine on 8 December 2008. The STI is very happy to have been part of these developments through its role as site partner to the Bagamoyo Research & Training Centre (BRTC) of the Ifakara Health Institute (IHI) that conducted the infant study (Abdulla et al. 2008).

Infant Study: Effective co-administration with EPI Vaccines (Abdullah et al 2008)   
The infant study enrolled 340 infants under 12 months of age in Tanzania and found that RTS,S/AS02, when administered at 8, 12, and 16 weeks of age with a commonly used childhood vaccine, did not interfere with the protective immune responses to each of the vaccine components. The childhood vaccine contained antigens for Diphtheria (D), Tetanus (T), whole-cell pertussis (Pw) and Haemophilus influenzae B (Hib). In countries where a malaria vaccine is needed most, the current immunization schedule for infants, called the WHO Expanded Program on Immunization (EPI), would provide an optimal delivery platform.

Researchers evaluated the safety and immune responses when administering the RTS,S/AS02 vaccine in conjunction with an EPI schedule. It was a randomized double-blind trial with participants simultaneously receiving either RTS,S/AS02 and DTP w/Hib as well as oral polio vaccine; or a hepatitis B vaccine and DTP w/Hib as well as oral polio vaccine.  

Additionally, the study reported 65 percent reduction against first infection from malaria in those infants who received three doses of the RTS,S/AS02 vaccine and were followed over a six-month period. This study builds upon results published in October 2007 in The Lancet, which found a similar level of efficacy for RTS,S/AS02 when it was given in a staggered fashion with the administration of DTPw/Hib vaccine (Aponte et al. 2007).

The trial was undertaken by the BRTC of IHI led by Dr. Salim Abdulla together with a team that included researchers from the STI, the London School of Hygiene and Tropical Medicine (LSHTM), GSK Biologicals, and MVI.

Child study: 53% efficacy against clinical malaria in children (Bejon et al. 2008)
The other trial enrolled 894 children 5-17 months old in both Kenya and Tanzania within the frame of the collaboration between KEMRI-Wellcome Collaborative Research Programme (Kilifi, Kenya), the National Institute for Medical Research (Tanzania), the Joint Malaria Programme (Korogwe, Tanzania), LSHTM and other institutions in collaboration with GSK and the MVI. The study was designed to evaluate the safety and efficacy of the RTS,S/AS, combined with another GSK’s proprietary Adjuvant System, coded AS01. The study was a double-blind randomized clinical trial in which children received either three doses of the RTS,S/AS01 vaccine candidate or a rabies vaccine.

It found that the RTS,S/AS01 formulation reduces clinical malaria episodes by 53 percent for up to an average of eight months. Earlier studies in Mozambique using RTS,S formulated with a different GSK Adjuvant System (AS02) demonstrated 35 percent efficacy against clinical disease for 18 months among children 1–4 years old. Researchers concluded that these study results support the use of RTS,S/AS01 for upcoming Phase 3 trials.

These studies open the way to a large scale phase-3 trial involving some 16’000 infants and small children in 11 centres in Africa. Pending approvals by national regulatory agencies and ethics committees, this multi-center phase III efficacy trial will start in early 2009. The trial will seek to confirm and evaluate with precision the vaccine’s efficacy, including duration, and will continue to closely monitor safety. The clinical development of RTS,S/AS is led by the Clinical Trial Partnership Committee, a collaboration of leading African research institutes, Northern academic partners with STI playing an important role, MVI and GSK with support from the Malaria Clinical Trial Alliance.  

Key references
Abdulla S, Oberholzer R, Juma O, et al. Safety and immunogenicity of RTS,S/AS02D malaria vaccine in infants. N Engl J Med 2008;359:2533-44.

Bejon P, Lusingu J, Olotu A, et al. Efficacy of RTS,S/AS01E: clinical malaria in 5 to 17 month old children. N Engl J Med 2008;359:

Aponte JJ, Aide P, Renom M, et al. Safety of the RTS,S/AS02D candidate malaria vaccine in infants living in a highly endemic area of Mozambique: a double blind randomised controlled phase I/IIb trial. Lancet 2007 Nov 3;370(9598):1543-51. Epub 2007 Oct 18.

 

Prof. Marcel Tanner

 

back to mainpage