title: Safety and allele-specific immunogenicity of a malaria vaccine in Malian adults: results of a phase I randomized trial.
abstract: OBJECTIVE
  The objectives were to evaluate the safety, reactogenicity, and allele-specific immunogenicity of the blood-stage malaria vaccine FMP1/AS02A in adults exposed to seasonal malaria and the impact of natural infection on vaccine-induced antibody levels.
  
  
  METHODS
  We conducted a randomized, double-blind, controlled phase I clinical trial.
  
  
  METHODS
  Bandiagara, Mali, West Africa, is a rural town with intense seasonal transmission of Plasmodium falciparum malaria.
  
  
  METHODS
  Forty healthy, malaria-experienced Malian adults aged 18-55 y were enrolled.
  
  
  METHODS
  The FMP1/AS02A malaria vaccine is a 42-kDa recombinant protein based on the carboxy-terminal end of merozoite surface protein-1 (MSP-1(42)) from the 3D7 clone of P. falciparum, adjuvanted with AS02A. The control vaccine was a killed rabies virus vaccine (Imovax). Participants were randomized to receive either FMP1/AS02A or rabies vaccine at 0, 1, and 2 mo and were followed for 1 y.
  
  
  METHODS
  Solicited and unsolicited adverse events and allele-specific antibody responses to recombinant MSP-1(42) and its subunits derived from P. falciparum strains homologous and heterologous to the 3D7 vaccine strain were measured.
  
  
  RESULTS
  Transient local pain and swelling were more common in the malaria vaccine group than in the control group (11/20 versus 3/20 and 10/20 versus 6/20, respectively). MSP-1(42) antibody levels rose during the malaria transmission season in the control group, but were significantly higher in malaria vaccine recipients after the second immunization and remained higher after the third immunization relative both to baseline and to the control group. Immunization with the malaria vaccine was followed by significant increases in antibodies recognizing three diverse MSP-1(42) alleles and their subunits.
  
  
  CONCLUSIONS
  FMP1/AS02A was well tolerated and highly immunogenic in adults exposed to intense seasonal malaria transmission and elicited immune responses to genetically diverse parasite clones. Anti-MSP-1(42) antibody levels followed a seasonal pattern that was significantly augmented and prolonged by the malaria vaccine.
authors.affiliation: Malaria Research and Training Center, University of Bamako, Bamako, Mali.
authors.forename: Mahamadou A
authors.initials: MA
authors.lastname: Thera
authors.forename: Ogobara K
authors.initials: OK
authors.lastname: Doumbo
authors.forename: Drissa
authors.initials: D
authors.lastname: Coulibaly
authors.forename: Dapa A
authors.initials: DA
authors.lastname: Diallo
authors.forename: Issaka
authors.initials: I
authors.lastname: Sagara
authors.forename: Alassane
authors.initials: A
authors.lastname: Dicko
authors.forename: David J
authors.initials: DJ
authors.lastname: Diemert
authors.forename: D Gray
authors.initials: DG
authors.lastname: Heppner
authors.forename: V Ann
authors.initials: VA
authors.lastname: Stewart
authors.forename: Evelina
authors.initials: E
authors.lastname: Angov
authors.forename: Lorraine
authors.initials: L
authors.lastname: Soisson
authors.forename: Amanda
authors.initials: A
authors.lastname: Leach
authors.forename: Kathryn
authors.initials: K
authors.lastname: Tucker
authors.forename: Kirsten E
authors.initials: KE
authors.lastname: Lyke
authors.forename: Christopher V
authors.initials: CV
authors.lastname: Plowe