RTS, S is a novel pre-erythrocytic malaria vaccine based on the circumsporozoite surface protein (CSP) of Plasmodium falciparum linked to hepatitis B surface antigen (HBs) and combined with a novel adjuvant system (SBAS2). We have conducted a Phase I trial with three doses of this vaccine given at 0, 1, and 6 months to 20 semiimmune, adult, male volunteers in The Gambia to assess its safety and immunogenicity. Eighteen of the 20 volunteers completed the study. There were no clinically significant local or systemic adverse events following each vaccination. Hematologic and biochemical indices before and two weeks after each vaccination showed no evidence of toxicity. Antibody titers to both CSP and HBs showed a significant increase after vaccination; these were the largest after the third dose. We conclude that the RTS, S/SBAS2 vaccine induces no significant toxicity in this semi-immune population and produces significant increases in antibody titers to CSP.

Immunity to malaria is poorly understood but is acquired gradually by people living in malaria-endemic parts of the world following repeated infections, but at a cost. Plasmodium falciparum malaria is responsible for the deaths of approximately 2,500,000 people each year, and most of these deaths occur in sub-Saharan Africa. 1 While interventions such as the use of insecticide-treated bed nets may reduce the mortality and morbidity associated with the disease, the sustainability of such an intervention has been questioned. The importance of an effective vaccine against P. falciparum malaria, to be used in conjunction with other control measures, cannot be over-emphasized. The only previous candidate malaria vaccine to enter Phase III field trials in endemic areas is SPf66, a vaccine targeting primarily the blood stage of the parasite. While the results of the first trials with this vaccine in Columbia2 and Tanzania3 were encouraging, subsequent trials in both The Gambia4 and Thailand5 showed that the efficacy of the vaccine was minimal. A novel vaccine candidate, designated RTS, S/SBAS2, was developed recently by SmithKline Beecham Biologicals (Rixensart, Belgium) and evaluated in phase I/IIa clinical studies in collaboration with the Walter Reed Army Institute of Research (WRAIR). This vaccine targets the pre-erythrocytic stage of the parasite. In human challenge studies performed at WRAIR, one particular formulation of this vaccine protected six of seven malaria-naıve volunteers against sporozoite challenge with a homologous NF54 strain of P. falciparum (clone 3D7) delivered via the bites of laboratory-reared mosquitoes. This result was statistically significant. 6