Development of the RTS,S/AS Vaccine Candidate from Concept to Phase III

This review describes the developmental history of the RTS,S/AS vaccine. Selection of the circumsporozoite protein (CSP) as the target antigen was key to the successful development of the vaccine so far, from concept to the initiation of Phase III testing. CSP, a pre-erythrocytic protective antigen against Plasmodium falciparum, has been demonstrated to be immunodominant and protective in pre-clinical studies both in animals and humans. The vaccine antigen was designated “RTS,S”; RTS being a hybrid polypeptide consisting of a portion of the CSP antigen and S the surface antigen of Hepatitis B virus (HBsAg). The RTS,S/AS candidate vaccine has been evaluated in multiple Phase I/II studies and shown to have a favourable safety profile and to be well tolerated in both adults and children. Consistent and significant efficacy against Plasmodium falciparum infection and disease was observed in the target population of infants and children in a range of age groups and in different malaria transmission settings. The RTS,S/AS01E malaria vaccine candidate has recently entered Phase III testing. Reaching this important milestone is the culmination of more than 20 years of research and development by GlaxoSmithKline, their partners and collaborators. If the Phase III results confirm the observations made during Phase II testing, the RTS,S/AS01E vaccine, when broadly implemented and judiciously integrated with other malaria-prevention measures, could have a major public-health impact in sub-Saharan Africa.