title: Phase 1 randomized controlled trial to evaluate the safety and immunogenicity of recombinant Pichia pastoris-expressed Plasmodium falciparum apical membrane antigen 1 (PfAMA1-FVO [25-545]) in healthy Malian adults in Bandiagara.
abstract: The safety and immunogenicity of PfAMA1, adjuvanted with Alhydrogel(®) was assessed in malaria-experienced Malian adults. The malaria vaccine, PfAMA1-FVO [25-545] is a recombinant protein Pichia pastoris-expressed AMA-1 from Plasmodium falciparum FVO clone adsorbed to Alhydrogel(®), the control vaccine was tetanus toxoid produced from formaldehyde detoxified and purified tetanus toxin.
  
  
  
  A double blind randomized controlled phase 1 study enrolled and followed 40 healthy adults aged 18-55 years in Bandiagara, Mali, West Africa, a rural setting with intense seasonal transmission of P. falciparum malaria. Volunteers were randomized to receive either 50 µg of malaria vaccine or the control vaccine. Three doses of vaccine were given on Days 0, 28 and 56, and participants were followed for 1 year. Solicited symptoms were assessed for seven days and unsolicited symptoms for 28 days after each vaccination. Serious adverse events were assessed throughout the study. The titres of anti-AMA-1 antibodies were measured by ELISA and P. falciparum growth inhibition assays were performed.
  
  
  
  Commonest local solicited adverse events were the injection site pain and swelling more frequent in the PfAMA1 group. No vaccine related serious adverse events were reported. A significant 3.5-fold increase of anti-AMA-1 IgG antibodies was observed in malaria vaccine recipients four weeks after the third immunization compared to the control group.
  
  
  
  The PfAMA1 showed a good safety profile. Most adverse events reported were of mild to moderate intensity. In addition, the vaccine induced a significant though short-lived increase in the anti-AMA1 IgG titres. Registered on www.clinicaltrials.gov with the number NCT00431808.
authors: Malaria Research and Training Centre, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine and Dentistry, University of Sciences, Techniques and Technologies, Bamako, Mali. mthera@icermali.org.
authors: Mahamadou A
authors: MA
authors: Thera
authors: Malaria Research and Training Centre, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine and Dentistry, University of Sciences, Techniques and Technologies, Bamako, Mali.
authors: Drissa
authors: D
authors: Coulibaly
authors: Malaria Research and Training Centre, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine and Dentistry, University of Sciences, Techniques and Technologies, Bamako, Mali.
authors: Abdoulaye K
authors: AK
authors: Kone
authors: Malaria Research and Training Centre, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine and Dentistry, University of Sciences, Techniques and Technologies, Bamako, Mali.
authors: Ando B
authors: AB
authors: Guindo
authors: Malaria Research and Training Centre, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine and Dentistry, University of Sciences, Techniques and Technologies, Bamako, Mali.
authors: Karim
authors: K
authors: Traore
authors: Malaria Research and Training Centre, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine and Dentistry, University of Sciences, Techniques and Technologies, Bamako, Mali.
authors: Abdourhamane H
authors: AH
authors: Sall
authors: Malaria Research and Training Centre, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine and Dentistry, University of Sciences, Techniques and Technologies, Bamako, Mali.
authors: Issa
authors: I
authors: Diarra
authors: Malaria Research and Training Centre, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine and Dentistry, University of Sciences, Techniques and Technologies, Bamako, Mali.
authors: Modibo
authors: M
authors: Daou
authors: Malaria Research and Training Centre, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine and Dentistry, University of Sciences, Techniques and Technologies, Bamako, Mali.
authors: Idrissa M
authors: IM
authors: Traore
authors: Malaria Research and Training Centre, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine and Dentistry, University of Sciences, Techniques and Technologies, Bamako, Mali.
authors: Youssouf
authors: Y
authors: Tolo
authors: Malaria Research and Training Centre, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine and Dentistry, University of Sciences, Techniques and Technologies, Bamako, Mali.
authors: Mady
authors: M
authors: Sissoko
authors: Malaria Research and Training Centre, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine and Dentistry, University of Sciences, Techniques and Technologies, Bamako, Mali.
authors: Amadou
authors: A
authors: Niangaly
authors: Malaria Research and Training Centre, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine and Dentistry, University of Sciences, Techniques and Technologies, Bamako, Mali.
authors: Charles
authors: C
authors: Arama
authors: Malaria Research and Training Centre, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine and Dentistry, University of Sciences, Techniques and Technologies, Bamako, Mali.
authors: Mounirou
authors: M
authors: Baby
authors: Malaria Research and Training Centre, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine and Dentistry, University of Sciences, Techniques and Technologies, Bamako, Mali.
authors: Bourema
authors: B
authors: Kouriba
authors: Malaria Research and Training Centre, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine and Dentistry, University of Sciences, Techniques and Technologies, Bamako, Mali.
authors: Mahamadou S
authors: MS
authors: Sissoko
authors: Malaria Research and Training Centre, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine and Dentistry, University of Sciences, Techniques and Technologies, Bamako, Mali.
authors: Issaka
authors: I
authors: Sagara
authors: Malaria Research and Training Centre, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine and Dentistry, University of Sciences, Techniques and Technologies, Bamako, Mali.
authors: Ousmane B
authors: OB
authors: Toure
authors: Malaria Research and Training Centre, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine and Dentistry, University of Sciences, Techniques and Technologies, Bamako, Mali.
authors: Amagana
authors: A
authors: Dolo
authors: Malaria Research and Training Centre, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine and Dentistry, University of Sciences, Techniques and Technologies, Bamako, Mali.
authors: Dapa A
authors: DA
authors: Diallo
authors: Biomedical Primate Research Center (BPRC), P.O. Box 3306, 2280 GH, Rijswijk, The Netherlands.
authors: Edmond
authors: E
authors: Remarque
authors: Center for Infectious Diseases Research in Zambia (CIDRZ), P.O. Box 34681, Lusaka, 10101, Zambia.
authors: Roma
authors: R
authors: Chilengi
authors: African Malaria Network Trust (AMANET), P.O. Box 33207, Dar Es Salaam, Tanzania.
authors: Ramadhani
authors: R
authors: Noor
authors: Medical Research Council, P.O. Box 273, Banjul, The Gambia.
authors: Sanie
authors: S
authors: Sesay
authors: Biomedical Primate Research Center (BPRC), P.O. Box 3306, 2280 GH, Rijswijk, The Netherlands.
authors: Alan
authors: A
authors: Thomas
authors: Biomedical Primate Research Center (BPRC), P.O. Box 3306, 2280 GH, Rijswijk, The Netherlands.
authors: Clemens H
authors: CH
authors: Kocken
authors: Biomedical Primate Research Center (BPRC), P.O. Box 3306, 2280 GH, Rijswijk, The Netherlands.
authors: Bart W
authors: BW
authors: Faber
authors: European Vaccine Initiative, European Vaccine Initiative, Im Neuenheimer Feld 307, 69120, Heidelberg, Germany.
authors: Egeruan Babatunde
authors: EB
authors: Imoukhuede
authors: European Vaccine Initiative, European Vaccine Initiative, Im Neuenheimer Feld 307, 69120, Heidelberg, Germany.
authors: Odile
authors: O
authors: Leroy
authors: Malaria Research and Training Centre, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine and Dentistry, University of Sciences, Techniques and Technologies, Bamako, Mali.
authors: Ogobara K
authors: OK
authors: Doumbo
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000293:Adolescent; D000328:Adult; D000536:Aluminum Hydroxide / Q000008:administration & dosage; D000913:Antibodies, Protozoan / Q000097:blood; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology*; D004311:Double-Blind Method; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015870:Gene Expression; D005822:Genetic Vectors; D064368:Healthy Volunteers; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000235:genetics / Q000276:immunology*; D008297:Male; D008302:Mali; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology*; D008875:Middle Aged; D010843:Pichia / Q000235:genetics*; D010963:Plasmodium falciparum / Q000235:genetics / Q000254:growth & development / Q000276:immunology*; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000276:immunology; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D007074:Immunoglobulin G; D017780:Malaria Vaccines; D008565:Membrane Proteins; D015800:Protozoan Proteins; D011994:Recombinant Proteins; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic; C090077:apical membrane antigen I, Plasmodium; D000536:Aluminum Hydroxide
keywords: Blood-stage; Immunogenicity; Malaria; PfAMA1; Plasmodium falciparum antigen; Safety; Vaccine