title: Efficacy of RTS,S/AS02 malaria vaccine against Plasmodium falciparum infection in semi-immune adult men in The Gambia: a randomised trial.
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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  RTS,S/AS02 is safe, immunogenic, and is the first pre-erythrocytic vaccine to show significant protection against natural P. falciparum infection.
authors.affiliation: Medical Research Council Laboratories, PO Box 273, The, Banjul, Gambia. kbojang@mrc.gm
authors.forename: K A
authors.initials: KA
authors.lastname: Bojang
authors.forename: P J
authors.initials: PJ
authors.lastname: Milligan
authors.forename: M
authors.initials: M
authors.lastname: Pinder
authors.forename: L
authors.initials: L
authors.lastname: Vigneron
authors.forename: A
authors.initials: A
authors.lastname: Alloueche
authors.forename: K E
authors.initials: KE
authors.lastname: Kester
authors.forename: W R
authors.initials: WR
authors.lastname: Ballou
authors.forename: D J
authors.initials: DJ
authors.lastname: Conway
authors.forename: W H
authors.initials: WH
authors.lastname: Reece
authors.forename: P
authors.initials: P
authors.lastname: Gothard
authors.forename: L
authors.initials: L
authors.lastname: Yamuah
authors.forename: M
authors.initials: M
authors.lastname: Delchambre
authors.forename: G
authors.initials: G
authors.lastname: Voss
authors.forename: B M
authors.initials: BM
authors.lastname: Greenwood
authors.forename: A
authors.initials: A
authors.lastname: Hill
authors.forename: K P
authors.initials: KP
authors.lastname: McAdam
authors.forename: N
authors.initials: N
authors.lastname: Tornieporth
authors.forename: J D
authors.initials: JD
authors.lastname: Cohen
authors.forename: T
authors.initials: T
authors.lastname: Doherty
mesh_terms: D000328:Adult; D000818:Animals; D000913:Antibodies, Protozoan / Q000032:analysis; D005714:Gambia / Q000453:epidemiology; D006801:Humans; D007114:Immunization; D017780:Malaria Vaccines / Q000008:administration & dosage*; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000276:immunology / Q000517:prevention & control*; D008297:Male; D010963:Plasmodium falciparum / Q000276:immunology*; D016016:Proportional Hazards Models; D015800:Protozoan Proteins; D011994:Recombinant Proteins; D018709:Statistics, Nonparametric; D016896:Treatment Outcome; D014614:Vaccines, Synthetic / Q000008:administration & dosage*
chemical_list: D000913:Antibodies, Protozoan; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D011994:Recombinant Proteins; C066269:SPf66 protein, Plasmodium; D014614:Vaccines, Synthetic