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RTS,S/AS02 is a recombinant protein malaria vaccine that contains a large portion of the C-terminal of the circumsporozoite protein (CSP) sequence of the NF54 isolate of Plasmodium falciparum fused to the hepatitis B virus surface antigen. It has been shown to induce significant protection to challenge infection with a homologous parasite strain in American volunteers. In a recently completed trial in semi-immune Gambian adults, vaccine efficacy against natural infection was 34% (95% confidence interval = 8–53%, P = 0.014) during the malaria season following vaccination. Breakthrough P. falciparum parasites sampled from vaccinated subjects and from controls were genotyped at two polymorphic regions of the csp gene encoding T cell epitopes (csp-th2r and csp-th3r) to determine if the vaccine conferred a strain-specific effect. The overall distribution of csp allelic variants was similar in infections occurring in vaccine and control groups. Also, the mean number of genotypes per infection in the RTS,S/AS02 group was not reduced compared with the controls.