title: Safety, immunogenicity and duration of protection of the RTS,S/AS02(D) malaria vaccine: one year follow-up of a randomized controlled phase I/IIb trial.
abstract: BACKGROUND
  The RTS,S/AS02(D) vaccine has been shown to have a promising safety profile, to be immunogenic and to confer protection against malaria in children and infants.
  
  
  RESULTS
  We did a randomized, controlled, phase I/IIb trial of RTS,S/AS02(D) given at 10, 14 and 18 weeks of age staggered with routine immunization vaccines in 214 Mozambican infants. The study was double-blind until the young child completed 6 months of follow-up over which period vaccine efficacy against new Plasmodium falciparum infections was estimated at 65.9% (95% CI 42.6-79.8, p<0.0001). We now report safety, immunogenicity and estimated efficacy against clinical malaria up to 14 months after study start. Vaccine efficacy was assessed using Cox regression models. The frequency of serious adverse events was 32.7% in the RTS,S/AS02(D) and 31.8% in the control group. The geometric mean titers of anti-circumsporozoite antibodies declined from 199.9 to 7.3 EU/mL from one to 12 months post dose three of RTS,S/AS02(D), remaining 15-fold higher than in the control group. Vaccine efficacy against clinical malaria was 33% (95% CI: -4.3-56.9, p = 0.076) over 14 months of follow-up. The hazard rate of disease per 2-fold increase in anti-CS titters was reduced by 84% (95% CI 35.1-88.2, p = 0.003).
  
  
  CONCLUSIONS
  The RTS,S/AS02(D) malaria vaccine administered to young infants has a good safety profile and remains efficacious over 14 months. A strong association between anti-CS antibodies and risk of clinical malaria has been described for the first time. The results also suggest a decrease of both anti-CS antibodies and vaccine efficacy over time.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00197028.
authors.affiliation: Centro de Investigação em Saúde da Manhiça, Maputo, Mozambique. pedro.aide@manhica.net
authors.forename: Pedro
authors.initials: P
authors.lastname: Aide
authors.forename: John J
authors.initials: JJ
authors.lastname: Aponte
authors.forename: Montse
authors.initials: M
authors.lastname: Renom
authors.forename: Tacilta
authors.initials: T
authors.lastname: Nhampossa
authors.forename: Jahit
authors.initials: J
authors.lastname: Sacarlal
authors.forename: Inacio
authors.initials: I
authors.lastname: Mandomando
authors.forename: Quique
authors.initials: Q
authors.lastname: Bassat
authors.forename: Maria Nélia
authors.initials: MN
authors.lastname: Manaca
authors.forename: Amanda
authors.initials: A
authors.lastname: Leach
authors.forename: Marc
authors.initials: M
authors.lastname: Lievens
authors.forename: Johan
authors.initials: J
authors.lastname: Vekemans
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Dubois
authors.forename: Christian
authors.initials: C
authors.lastname: Loucq
authors.forename: W Ripley
authors.initials: WR
authors.lastname: Ballou
authors.forename: Joe
authors.initials: J
authors.lastname: Cohen
authors.forename: Pedro L
authors.initials: PL
authors.lastname: Alonso
mesh_terms: D000913:Antibodies, Protozoan / Q000032:analysis / Q000276:immunology; D002675:Child, Preschool; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D005334:Fever / Q000139:chemically induced; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D016778:Malaria, Falciparum / Q000276:immunology* / Q000517:prevention & control; D009073:Mozambique / Q000453:epidemiology; D018512:Parasitemia / Q000276:immunology / Q000517:prevention & control; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology; D012894:Sleep Stages / Q000187:drug effects; D013997:Time Factors; D016896:Treatment Outcome; D014611:Vaccination / Q000379:methods
chemical_list: D000913:Antibodies, Protozoan; D017780:Malaria Vaccines; D015800:Protozoan Proteins; C041595:circumsporozoite protein, Protozoan