title: Safety and immunogenicity of RTS,S/AS02D malaria vaccine in infants.
abstract: BACKGROUND
  The RTS,S/AS malaria vaccine is being developed for delivery through the World Health Organization's Expanded Program on Immunization (EPI). We assessed the feasibility of integrating RTS,S/AS02D into a standard EPI schedule for infants.
  
  
  METHODS
  In this phase 2B, single-center, double-blind, controlled trial involving 340 infants in Bagamoyo, Tanzania, we randomly assigned 340 infants to receive three doses of either the RTS,S/AS02D vaccine or the hepatitis B vaccine at 8, 12, and 16 weeks of age. All infants also received a vaccine containing diphtheria and tetanus toxoids, whole-cell pertussis vaccine, and conjugated Haemophilus influenzae type b vaccine (DTPw/Hib). The primary objectives were the occurrence of serious adverse events during a 9-month surveillance period and a demonstration of noninferiority of the responses to the EPI vaccines (DTPw/Hib and hepatitis B surface antigen) with coadministration of the RTS,S/AS02D vaccine, as compared with the hepatitis B vaccine. The detection of antibodies against Plasmodium falciparum circumsporozoite and efficacy against malaria infection were secondary objectives.
  
  
  RESULTS
  At least one serious adverse event was reported in 31 of 170 infants who received the RTS,S/AS02D vaccine (18.2%; 95% confidence interval [CI], 12.7 to 24.9) and in 42 of 170 infants who received the hepatitis B vaccine (24.7%; 95% CI, 18.4 to 31.9). The results showed the noninferiority of the RTS,S/AS02D vaccine in terms of antibody responses to EPI antigens. One month after vaccination, 98.6% of infants receiving the RTS,S/AS02D vaccine had seropositive titers for anticircumsporozoite antibodies on enzyme-linked immunosorbent assay (ELISA). During the 6-month period after the third dose of vaccine, the efficacy of the RTS,S/AS02D vaccine against first infection with P. falciparum malaria was 65.2% (95% CI, 20.7 to 84.7; P=0.01).
  
  
  CONCLUSIONS
  The use of the RTS,S/AS02D vaccine in infants had a promising safety profile, did not interfere with the immunologic responses to coadministered EPI antigens, and reduced the incidence of malaria infection. (ClinicalTrials.gov number, NCT00289185.)
authors.affiliation: Bagamoyo Research and Training Centre of Ifakara Health Institute, Bagamoyo, Tanzania. sabdulla@ihi.or.tz
authors.forename: Salim
authors.initials: S
authors.lastname: Abdulla
authors.forename: Rolf
authors.initials: R
authors.lastname: Oberholzer
authors.forename: Omar
authors.initials: O
authors.lastname: Juma
authors.forename: Sulende
authors.initials: S
authors.lastname: Kubhoja
authors.forename: Francisca
authors.initials: F
authors.lastname: Machera
authors.forename: Christopher
authors.initials: C
authors.lastname: Membi
authors.forename: Said
authors.initials: S
authors.lastname: Omari
authors.forename: Alwisa
authors.initials: A
authors.lastname: Urassa
authors.forename: Hassan
authors.initials: H
authors.lastname: Mshinda
authors.forename: Ajuza
authors.initials: A
authors.lastname: Jumanne
authors.forename: Nahya
authors.initials: N
authors.lastname: Salim
authors.forename: Mwanjaa
authors.initials: M
authors.lastname: Shomari
authors.forename: Thomas
authors.initials: T
authors.lastname: Aebi
authors.forename: David M
authors.initials: DM
authors.lastname: Schellenberg
authors.forename: Terrell
authors.initials: T
authors.lastname: Carter
authors.forename: Tonya
authors.initials: T
authors.lastname: Villafana
authors.forename: Marie-Ange
authors.initials: MA
authors.lastname: Demoitié
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Dubois
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: Joe
authors.initials: J
authors.lastname: Cohen
authors.forename: W Ripley
authors.initials: WR
authors.lastname: Ballou
authors.forename: Marcel
authors.initials: M
authors.lastname: Tanner
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D001428:Bacterial Vaccines; D004311:Double-Blind Method; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000276:immunology / Q000517:prevention & control*; D008297:Male; D010963:Plasmodium falciparum / Q000276:immunology; D015800:Protozoan Proteins / Q000276:immunology
chemical_list: D000913:Antibodies, Protozoan; D001428:Bacterial Vaccines; D006514:Hepatitis B Surface Antigens; D017780:Malaria Vaccines; D015800:Protozoan Proteins; C533817:RTS,S-AS02D vaccine; C041595:circumsporozoite protein, Protozoan