title: Evaluation of the safety and immunogenicity of the RTS,S/AS01E malaria candidate vaccine when integrated in the expanded program of immunization.
abstract: BACKGROUND
  The RTS,S/AS01(E) malaria candidate vaccine is being developed for immunization of African infants through the Expanded Program of Immunization (EPI).
  
  
  METHODS
  This phase 2, randomized, open, controlled trial conducted in Ghana, Tanzania, and Gabon evaluated the safety and immunogenicity of RTS,S/AS01(E) when coadministered with EPI vaccines. Five hundred eleven infants were randomized to receive RTS,S/AS01(E) at 0, 1, and 2 months (in 3 doses with diphtheria, tetanus, and whole-cell pertussis conjugate [DTPw]; hepatitis B [HepB]; Haemophilus influenzae type b [Hib]; and oral polio vaccine [OPV]), RTS,S/AS01(E) at 0, 1, and 7 months (2 doses with DTPwHepB/Hib+OPV and 1 dose with measles and yellow fever), or EPI vaccines only.
  
  
  RESULTS
  The occurrences of serious adverse events were balanced across groups; none were vaccine-related. One child from the control group died. Mild to moderate fever and diaper dermatitis occurred more frequently in the RTS,S/AS01(E) coadministration groups. RTS,S/AS01(E) generated high anti-circumsporozoite protein and anti-hepatitis B surface antigen antibody levels. Regarding EPI vaccine responses upon coadministration when considering both immunization schedules, despite a tendency toward lower geometric mean titers to some EPI antigens, predefined noninferiority criteria were met for all EPI antigens except for polio 3 when EPI vaccines were given with RTS,S/AS01(E) at 0, 1, and 2 months. However, when antibody levels at screening were taken into account, the rates of response to polio 3 antigens were comparable between groups.
  
  
  CONCLUSIONS
  RTS,S/AS01(E) integrated in the EPI showed a favorable safety and immunogenicity evaluation. Trial registration. ClinicalTrials.gov identifier: NCT00436007 . GlaxoSmithKline study ID number: 106369 (Malaria-050).
authors.affiliation: Albert Schweitzer Hospital, Medical Research Unit Lambaréné, Lambaréné, Gabon. agnandjis@yahoo.fr
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authors.forename: Marie-Ange
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authors.lastname: Demoitié
authors.forename: Marie-Claude
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authors.lastname: Tanner
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mesh_terms: D016667:Bacterial Capsules / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D015721:Diphtheria-Tetanus-Pertussis Vaccine / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D005260:Female; D005681:Gabon; D005869:Ghana; D018073:Haemophilus Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D017325:Hepatitis B Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D006801:Humans; D007114:Immunization / Q000379:methods*; D007117:Immunization, Secondary / Q000379:methods; D007223:Infant; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D008297:Male; D011055:Poliovirus Vaccine, Oral / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D013636:Tanzania
chemical_list: D015721:Diphtheria-Tetanus-Pertussis Vaccine; D018073:Haemophilus Vaccines; C044237:Haemophilus influenzae type b polysaccharide vaccine; D017325:Hepatitis B Vaccines; D017780:Malaria Vaccines; D011055:Poliovirus Vaccine, Oral; C533816:RTS,S-AS01E vaccine