Efficacy of RTS,S/ASO2 malaria vaccine against Plasmodium falciparum infection in semi-immune adult men in The Gambia: a randomised trial


Bojang, KA; Milligan, PJM; Pinder, M; Vigneron, L; Alloueche, A; Kester, KE; Ballou, WR; Conway, DJ; Reece, WHH; Gothard, P; Yamuah, L; Delchambre, M; Voss, G; Greenwood, BM; Hill, A; McAdam, K; Tornieporth, N; Cohen, JD; Doherty, T; (2001) Efficacy of RTS,S/ASO2 malaria vaccine against Plasmodium falciparum infection in semi-immune adult men in The Gambia: a randomised trial. Lancet, 358 (9297). pp. 1927-1934. ISSN 0140-6736 DOI: https://doi.org/10.1016/S0140-6736(01)06957-4

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Abstract

Background 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. Methods 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. Findings 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). Interpretation RTS,S/AS02 is safe, immunogenic, and is the first pre-erythrocytic vaccine to show significant protection against natural P falciparum infection.

Item Type: Article
Keywords: Circumsporozoite-protein, spf66 vaccine, west-africa, safety, immunogenicity, sporozoites, heterogeneity, immunization, rts, s/sbas2, protection, Adult, Animal, Antibodies, Protozoan, analysis, Gambia, epidemiology, Human, Immunization, Malaria Vaccines, administration & dosage, Malaria, Falciparum, epidemiology, immunology, prevention & control, Male, Plasmodium falciparum, immunology, Proportional Hazards Models, Protozoan Proteins, Statistics, Nonparametric, Support, Non-U.S. Gov't, Treatment Outcome, Vaccines, Synthetic, administration & dosage
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Clinical Research
Faculty of Infectious and Tropical Diseases > Dept of Pathogen Molecular Biology
Faculty of Infectious and Tropical Diseases > Dept of Disease Control
Faculty of Infectious and Tropical Diseases > Dept of Immunology and Infection
Faculty of Epidemiology and Population Health > Dept of Infectious Disease Epidemiology
Research Centre: Malaria Centre
Tropical Epidemiology Group
PubMed ID: 11747915
Web of Science ID: 172622200008
URI: http://researchonline.lshtm.ac.uk/id/eprint/16433

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