title: Safety and immunogenicity of the RTS,S/AS02A candidate malaria vaccine in children aged 1-4 in Mozambique.
abstract: BACKGROUND
  The development of a malaria vaccine remains a public health priority for sub-Saharan Africa. RTS,S/AS02A candidate malaria vaccine has been shown to be safe and immunogenic in previous studies in adults and staggered dose-escalation studies in children in The Gambia. However, genetic features and the intensity of malaria transmission may modify the safety and immune response of a vaccine.
  
  
  OBJECTIVE
  We carried out a phase I, double-blind randomized controlled trial in 60 children aged 1-4 in Mozambique to evaluate the safety, reactogenicity and immunogenicity of the paediatric vaccine dose (fixed 25 microg RTS,S in 0.25 ml) of RTS,S/AS02A, prior to undertaking a planned larger phase IIb proof-of-concept of efficacy study in the same population.
  
  
  METHODS
  Children were randomized to receive either RTS,S/AS02A or Engerix-B vaccine. Monitoring of safety and reactogenicity included detailed clinical and laboratory analyses and assessment of adverse events (AEs).
  
  
  RESULTS
  The RTS,S/AS02A was found to be safe and well tolerated. Serious adverse events were balanced between both groups and none was related to vaccination. The frequency of adverse events reported with RTS, S/AS02A was comparable to previous studies in children. Grade 3 AEs were infrequent (one case of pain, one of fever in each group and some swelling greater than 20 mm in diameter), transient and resolved without sequelae. RTS,S/AS02A was highly immunogenic for anti-circumsporozoite protein antibody response and induced a strong anti-hepatitis-B surface antigen response.
authors.affiliation: Centro de Investigação em Saúde da Manhiça (CISM), Manhiça, Mozambique.
authors.forename: E
authors.initials: E
authors.lastname: Macete
authors.forename: J J
authors.initials: JJ
authors.lastname: Aponte
authors.forename: C
authors.initials: C
authors.lastname: Guinovart
authors.forename: J
authors.initials: J
authors.lastname: Sacarlal
authors.forename: O
authors.initials: O
authors.lastname: Ofori-Anyinam
authors.forename: I
authors.initials: I
authors.lastname: Mandomando
authors.forename: M
authors.initials: M
authors.lastname: Espasa
authors.forename: C
authors.initials: C
authors.lastname: Bevilacqua
authors.forename: A
authors.initials: A
authors.lastname: Leach
authors.forename: M C
authors.initials: MC
authors.lastname: Dubois
authors.forename: D G
authors.initials: DG
authors.lastname: Heppner
authors.forename: L
authors.initials: L
authors.lastname: Tello
authors.forename: J
authors.initials: J
authors.lastname: Milman
authors.forename: J
authors.initials: J
authors.lastname: Cohen
authors.forename: F
authors.initials: F
authors.lastname: Dubovsky
authors.forename: N
authors.initials: N
authors.lastname: Tornieporth
authors.forename: R
authors.initials: R
authors.lastname: Thompson
authors.forename: P L
authors.initials: PL
authors.lastname: Alonso
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000913:Antibodies, Protozoan / Q000276:immunology; D002675:Child, Preschool; D003404:Creatinine / Q000097:blood; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D006505:Hepatitis / Q000276:immunology; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D017325:Hepatitis B Vaccines / Q000009:adverse effects / Q000276:immunology; D006801:Humans; D007223:Infant; D007267:Injections / Q000009:adverse effects; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000276:immunology / Q000517:prevention & control; D009073:Mozambique / Q000453:epidemiology; D010146:Pain / Q000139:chemically induced; D015800:Protozoan Proteins / Q000276:immunology
chemical_list: D000913:Antibodies, Protozoan; C075654:Engerix-B; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D017780:Malaria Vaccines; D015800:Protozoan Proteins; C493155:RTS,S-AS02A vaccine; C041595:circumsporozoite protein, Protozoan; D003404:Creatinine; D000410:Alanine Transaminase