Publications (2)40.87 Total impact
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Article: Efficacy of RTS,S/AS02 malaria vaccine against Plasmodium falciparum infection in semi-immune adult men in The Gambia: a randomised trial.
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ABSTRACT: RTS,S/AS02 is a pre-erythrocytic malaria vaccine based on the circumsporozoite surface protein of Plasmodium falciparum fused to HBsAg, incorporating a new adjuvant (AS02). We did a randomised trial of the efficacy of RTS,S/AS02 against natural P. falciparum infection in semi-immune adult men in The Gambia. 306 men aged 18-45 years were randomly assigned three doses of either RTS,S/AS02 or rabies vaccine (control). Volunteers were given sulfadoxine/pyrimethamine 2 weeks before dose 3, and kept under surveillance throughout the malaria transmission season. Blood smears were collected once a week and whenever a volunteer developed symptoms compatible with malaria. The primary endpoint was time to first infection with P. falciparum. Analysis was per protocol. 250 men (131 in the RTS,S/AS02 group and 119 in the control group) received three doses of vaccine and were followed up for 15 weeks. RTS,S/AS02 was safe and well tolerated. P. falciparum infections occurred significantly earlier in the control group than the RTS,S/AS02 group (Wilcoxon's test p=0.018). Vaccine efficacy, adjusted for confounders, was 34% (95% CI 8.0-53, p=0.014). Protection seemed to wane: estimated efficacy during the first 9 weeks of follow-up was 71% (46-85), but decreased to 0% (-52 to 34) in the last 6 weeks. Vaccination induced strong antibody responses to circumsporozoite protein and strong T-cell responses. Protection was not limited to the NF54 parasite genotype from which the vaccine was derived. 158 men received a fourth dose the next year and were followed up for 9 weeks; during this time, vaccine efficacy was 47% (4-71, p=0.037). RTS,S/AS02 is safe, immunogenic, and is the first pre-erythrocytic vaccine to show significant protection against natural P. falciparum infection.The Lancet 01/2002; 358(9297):1927-34. · 38.28 Impact Factor -
Article: A phase I safety and immunogenicity trial with the candidate malaria vaccine RTS,S/SBAS2 in semi-immune adults in The Gambia.
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ABSTRACT: 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 semi-immune, 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.The American journal of tropical medicine and hygiene 01/2000; 61(6):865-8. · 2.59 Impact Factor
