title: Long-term safety and efficacy of the RTS,S/AS02A malaria vaccine in Mozambican children.
abstract: BACKGROUND
  We previously reported that the RTS,S/AS02A vaccine had an acceptable safety profile, was immunogenic, and demonstrated efficacy against Plasmodium falciparum malaria disease for 21 months.
  
  
  METHODS
  We conducted a randomized, controlled, phase 2b trial of RTS,S/AS02A in 2022 Mozambican children aged 1-4 years. We now report safety results for all randomized subjects and vaccine efficacy (VE) findings for children in the Manhiça area over the 45-month surveillance period.
  
  
  RESULTS
  During the surveillance period, the VE((2.5-45)) (VE over months 2.5-45 of surveillance) against a first or only episode of clinical malaria disease was 30.5% (95% confidence interval [CI], 18.9%-40.4%; P < .001), and the VE((2.5-45)) against all episodes was 25.6% (95% CI, 11.9%-37.1%; P < .001). When the same period was considered, the VE((2.5-45)) for subjects protected against severe malaria was 38.3% (95% CI, 3.4%-61.3%; P = .045). At study month 45, the prevalence of P. falciparum was 34% lower in the RTS,S/AS02A group than in the control group (66 [12.2%] of 541 patients vs 101 [18.5%] of 547 patients) (P = .004).
  
  
  CONCLUSIONS
  These results show evidence that RTS,S/AS02A maintained protection during the 45-month surveillance period, and they highlight the feasibility of developing an effective vaccine against malaria. In combination with other malaria-control measures, such a vaccine could greatly contribute to reducing the intolerable global burden of this disease. Trial registration. ClinicalTrials.gov identifiers NCT00197041 and NCT00323622 .
authors: Centro de Investigação em Saúde de Manhiça (CISM) Manhiça, Mozambique. jahit.sacarlal@manhica.net
authors: Jahit
authors: J
authors: Sacarlal
authors: Pedro
authors: P
authors: Aide
authors: John J
authors: JJ
authors: Aponte
authors: Montse
authors: M
authors: Renom
authors: Amanda
authors: A
authors: Leach
authors: Inácio
authors: I
authors: Mandomando
authors: Marc
authors: M
authors: Lievens
authors: Quique
authors: Q
authors: Bassat
authors: Sarah
authors: S
authors: Lafuente
authors: Eusébio
authors: E
authors: Macete
authors: Johan
authors: J
authors: Vekemans
authors: Caterina
authors: C
authors: Guinovart
authors: Betuel
authors: B
authors: Sigaúque
authors: Marla
authors: M
authors: Sillman
authors: Jessica
authors: J
authors: Milman
authors: Marie-Claude
authors: MC
authors: Dubois
authors: Marie-Ange
authors: MA
authors: Demoitié
authors: Joelle
authors: J
authors: Thonnard
authors: Clara
authors: C
authors: Menéndez
authors: W Ripley
authors: WR
authors: Ballou
authors: Joe
authors: J
authors: Cohen
authors: Pedro L
authors: PL
authors: Alonso
mesh_terms: D000913:Antibodies, Protozoan / Q000097:blood; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D017780:Malaria Vaccines / Q000009:adverse effects* / Q000276:immunology / Q000592:standards*; D016778:Malaria, Falciparum / Q000276:immunology / Q000517:prevention & control*; D009073:Mozambique / Q000453:epidemiology; D018512:Parasitemia; D013997:Time Factors
chemical_list: D000913:Antibodies, Protozoan; D017780:Malaria Vaccines