The RTS,S/AS01(E) malaria vaccine candidate has recently entered Phase 3 
testing. Reaching this important milestone is the culmination of more than 20 
years of research and development by GlaxoSmithKline and partners and 
collaborators. The vaccine has been developed to protect young children and 
infants living in Sub-Saharan Africa against clinical and severe disease caused 
by Plasmodium falciparum infection. Over the past 9 years, RTS,S/AS has been 
evaluated in multiple Phase 2 studies. The vaccine was shown to have a favorable 
safety profile and to be well tolerated in all age groups in which it was 
tested, including the intended target population of infants and young children 
in Sub-Saharan Africa. Data obtained so far suggest that RTS,S/AS can be 
co-administered with other vaccines included in the routine Expanded Program of 
Immunization (EPI). In Phase 2 testing, the vaccine candidate was shown to 
confer significant protection against P. falciparum infection and clinical 
disease, including severe malaria. Furthermore, a trend towards an indirect 
beneficial effect of the vaccine on non-malarial morbidities has been observed 
in several trials. In this paper, we will describe the genesis of the RTS,S/AS 
concept, including the rationale for selecting the circumsporozoite protein 
(CSP) as the target antigen. Early development history of the vaccine will be 
briefly described. We will present the most salient results from recent Phase 2 
studies conducted in the target pediatric population, which have led to the 
decision to progress RTS,S/AS to Phase 3 testing. If the Phase 3 results confirm 
the observations made during Phase 2 testing, the RTS,S/AS vaccine, when broadly 
implemented and judiciously integrated with other malaria-prevention measures, 
would have a major public-health impact in Sub-Saharan Africa.