title: Safety of the RTS,S/AS02A malaria vaccine in Mozambican children during a Phase IIb trial.
abstract: RTS,S/AS02A is a pre-erythrocytic vaccine candidate based on the Plasmodium falciparum circumsporozoite surface antigen and is currently the most advanced malaria vaccine candidate in development. A proof of concept phase IIb trial of the RTS,S/AS02A in Mozambican children aged 1-4 years determined a vaccine efficacy against risk of clinical malaria of 35.3% (95% CI 21.6-46.6; p<0.0001) and against severe malaria of 48.6% (95% CI 12.3-71.0; p=0.02). We evaluated the safety of the RTS,S/AS02A vaccine. 2022 children that received at least one vaccine dose of RTS,S/AS02A or control vaccines were included in the intention to treat safety analysis. Vaccine safety was evaluated using active and passive follow-up. Participants were observed for at least 1h after each dose. Trained field workers visited children at home daily for the next 3 days to record solicited and unsolicited local and general symptoms. Investigators followed-up participants with severe adverse events until month 21. Overall, we recorded 1712 unsolicited adverse events after vaccination, 53% in the intervention and 47% in the control group. Most unsolicited adverse events reported with RTS,S/AS02A were self-limited, and participants recovered without sequelae. Local reactogenicity increased with the number of doses. The proportion of children experiencing serious adverse events was lower in the RTS,S/AS02A recipients compared to the control group (Engerix-Btrade mark or Prevnartrade mark and Hiberixtrade mark). Overall, these results indicate that the RTS,S/AS02A vaccine has a good safety profile and well tolerated when given in three doses to semi-immune children living in malaria-endemic areas.
authors: Centro de Investigação em Saúde de Manhiça, Manhiça, Mozambique. Jahit.sacarlal@manhica.net <Jahit.sacarlal@manhica.net>
authors: Jahit
authors: J
authors: Sacarlal
authors: John J
authors: JJ
authors: Aponte
authors: Pedro
authors: P
authors: Aide
authors: Inácio
authors: I
authors: Mandomando
authors: Quique
authors: Q
authors: Bassat
authors: Caterina
authors: C
authors: Guinovart
authors: Amanda
authors: A
authors: Leach
authors: Jessica
authors: J
authors: Milman
authors: Eusebio
authors: E
authors: Macete
authors: Mateu
authors: M
authors: Espasa
authors: Opokua
authors: O
authors: Ofori-Anyinam
authors: Joelle
authors: J
authors: Thonnard
authors: Sabine
authors: S
authors: Corachan
authors: Marie-Claude
authors: MC
authors: Dubois
authors: Marc
authors: M
authors: Lievens
authors: Filip
authors: F
authors: Dubovsky
authors: W Ripley
authors: WR
authors: Ballou
authors: Joe
authors: J
authors: Cohen
authors: Pedro L
authors: PL
authors: Alonso
mesh_terms: D002675:Child, Preschool; D004311:Double-Blind Method; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; 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
chemical_list: D017780:Malaria Vaccines; C493155:RTS,S-AS02A vaccine