title: Extended safety, immunogenicity and efficacy of a blood-stage malaria vaccine in malian children: 24-month follow-up of a randomized, double-blinded phase 2 trial.
abstract: BACKGROUND
  The FMP2.1/AS02A candidate malaria vaccine was tested in a Phase 2 study in Mali. Based on results from the first eight months of follow-up, the vaccine appeared well-tolerated and immunogenic. It had no significant efficacy based on the primary endpoint, clinical malaria, but marginal efficacy against clinical malaria in secondary analyses, and high allele-specific efficacy. Extended follow-up was conducted to evaluate extended safety, immunogenicity and efficacy.
  
  
  METHODS
  A randomized, double-blinded trial of safety, immunogenicity and efficacy of the candidate Plasmodium falciparum apical membrane antigen 1 (AMA1) vaccine FMP2.1/AS02A was conducted in Bandiagara, Mali. Children aged 1-6 years were randomized in a 1∶1 ratio to receive FMP2.1/AS02A or control rabies vaccine on days 0, 30 and 60. Using active and passive surveillance, clinical malaria and adverse events as well as antibodies against P. falciparum AMA1 were monitored for 24 months after the first vaccination, spanning two malaria seasons.
  
  
  RESULTS
  400 children were enrolled. Serious adverse events occurred in nine participants in the FMP2.1/AS02A group and three in the control group; none was considered related to study vaccination. After two years, anti-AMA1 immune responses remained significantly higher in the FMP2.1/AS02A group than in the control group. For the entire 24-month follow-up period, vaccine efficacy was 7.6% (p = 0.51) against first clinical malaria episodes and 9.9% (p = 0.19) against all malaria episodes. For the final 16-month follow-up period, vaccine efficacy was 0.9% (p = 0.98) against all malaria episodes. Allele-specific efficacy seen in the first malaria season did not extend into the second season of follow-up.
  
  
  CONCLUSIONS
  Allele-specific vaccine efficacy was not sustained in the second malaria season, despite continued high levels of anti-AMA1 antibodies. This study presents an opportunity to evaluate correlates of partial protection against clinical malaria that waned during the second malaria season.
  
  
  BACKGROUND
  Clinicaltrials.gov NCT00460525 NCT00460525.
authors.affiliation: Malaria Group, Howard Hughes Medical Institute/Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Laurens
authors.forename: Mahamadou A
authors.initials: MA
authors.lastname: Thera
authors.forename: Drissa
authors.initials: D
authors.lastname: Coulibaly
authors.forename: Amed
authors.initials: A
authors.lastname: Ouattara
authors.forename: Abdoulaye K
authors.initials: AK
authors.lastname: Kone
authors.forename: Ando B
authors.initials: AB
authors.lastname: Guindo
authors.forename: Karim
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authors.lastname: Traore
authors.forename: Idrissa
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authors.lastname: Traore
authors.forename: Bourema
authors.initials: B
authors.lastname: Kouriba
authors.forename: Dapa A
authors.initials: DA
authors.lastname: Diallo
authors.forename: Issa
authors.initials: I
authors.lastname: Diarra
authors.forename: Modibo
authors.initials: M
authors.lastname: Daou
authors.forename: Amagana
authors.initials: A
authors.lastname: Dolo
authors.forename: Youssouf
authors.initials: Y
authors.lastname: Tolo
authors.forename: Mahamadou S
authors.initials: MS
authors.lastname: Sissoko
authors.forename: Amadou
authors.initials: A
authors.lastname: Niangaly
authors.forename: Mady
authors.initials: M
authors.lastname: Sissoko
authors.forename: Shannon
authors.initials: S
authors.lastname: Takala-Harrison
authors.forename: Kirsten E
authors.initials: KE
authors.lastname: Lyke
authors.forename: Yukun
authors.initials: Y
authors.lastname: Wu
authors.forename: William C
authors.initials: WC
authors.lastname: Blackwelder
authors.forename: Olivier
authors.initials: O
authors.lastname: Godeaux
authors.forename: Johan
authors.initials: J
authors.lastname: Vekemans
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Dubois
authors.forename: W Ripley
authors.initials: WR
authors.lastname: Ballou
authors.forename: Joe
authors.initials: J
authors.lastname: Cohen
authors.forename: Tina
authors.initials: T
authors.lastname: Dube
authors.forename: Lorraine
authors.initials: L
authors.lastname: Soisson
authors.forename: Carter L
authors.initials: CL
authors.lastname: Diggs
authors.forename: Brent
authors.initials: B
authors.lastname: House
authors.forename: Jason W
authors.initials: JW
authors.lastname: Bennett
authors.forename: David E
authors.initials: DE
authors.lastname: Lanar
authors.forename: Sheetij
authors.initials: S
authors.lastname: Dutta
authors.forename: D Gray
authors.initials: DG
authors.lastname: Heppner
authors.forename: Christopher V
authors.initials: CV
authors.lastname: Plowe
authors.forename: Ogobara K
authors.initials: OK
authors.lastname: Doumbo
mesh_terms: D000483:Alleles; D000953:Antigens, Protozoan / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D017780:Malaria Vaccines / Q000276:immunology*; D016778:Malaria, Falciparum / Q000276:immunology* / Q000517:prevention & control*; D008297:Male; D008302:Mali; D010963:Plasmodium falciparum / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity
chemical_list: D000953:Antigens, Protozoan; D017780:Malaria Vaccines