title: Impact on malaria parasite multiplication rates in infected volunteers of the protein-in-adjuvant vaccine AMA1-C1/Alhydrogel+CPG 7909.
abstract: BACKGROUND
  Inhibition of parasite growth is a major objective of blood-stage malaria vaccines. The in vitro assay of parasite growth inhibitory activity (GIA) is widely used as a surrogate marker for malaria vaccine efficacy in the down-selection of candidate blood-stage vaccines. Here we report the first study to examine the relationship between in vivo Plasmodium falciparum growth rates and in vitro GIA in humans experimentally infected with blood-stage malaria.
  
  
  METHODS
  In this phase I/IIa open-label clinical trial five healthy malaria-naive volunteers were immunised with AMA1/C1-Alhydrogel+CPG 7909, and together with three unvaccinated controls were challenged by intravenous inoculation of P. falciparum infected erythrocytes.
  
  
  RESULTS
  A significant correlation was observed between parasite multiplication rate in 48 hours (PMR) and both vaccine-induced growth-inhibitory activity (Pearson r = -0.93 [95% CI: -1.0, -0.27] P = 0.02) and AMA1 antibody titres in the vaccine group (Pearson r = -0.93 [95% CI: -0.99, -0.25] P = 0.02). However immunisation failed to reduce overall mean PMR in the vaccine group in comparison to the controls (vaccinee 16 fold [95% CI: 12, 22], control 17 fold [CI: 0, 65] P = 0.70). Therefore no impact on pre-patent period was observed (vaccine group median 8.5 days [range 7.5-9], control group median 9 days [range 7-9]).
  
  
  CONCLUSIONS
  Despite the first observation in human experimental malaria infection of a significant association between vaccine-induced in vitro growth inhibitory activity and in vivo parasite multiplication rate, this did not translate into any observable clinically relevant vaccine effect in this small group of volunteers.
  
  
  BACKGROUND
  ClinicalTrials.gov [NCT00984763].
authors.affiliation: Centre for Clinical Vaccinology and Tropical Medicine, The Jenner Institute, University of Oxford, Oxford, United Kingdom. christopher.duncan@ndm.ox.ac.uk
authors.forename: Christopher J A
authors.initials: CJ
authors.lastname: Duncan
authors.forename: Susanne H
authors.initials: SH
authors.lastname: Sheehy
authors.forename: Katie J
authors.initials: KJ
authors.lastname: Ewer
authors.forename: Alexander D
authors.initials: AD
authors.lastname: Douglas
authors.forename: Katharine A
authors.initials: KA
authors.lastname: Collins
authors.forename: Fenella D
authors.initials: FD
authors.lastname: Halstead
authors.forename: Sean C
authors.initials: SC
authors.lastname: Elias
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Lillie
authors.forename: Kelly
authors.initials: K
authors.lastname: Rausch
authors.forename: Joan
authors.initials: J
authors.lastname: Aebig
authors.forename: Kazutoyo
authors.initials: K
authors.lastname: Miura
authors.forename: Nick J
authors.initials: NJ
authors.lastname: Edwards
authors.forename: Ian D
authors.initials: ID
authors.lastname: Poulton
authors.forename: Angela
authors.initials: A
authors.lastname: Hunt-Cooke
authors.forename: David W
authors.initials: DW
authors.lastname: Porter
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Thompson
authors.forename: Ros
authors.initials: R
authors.lastname: Rowland
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Draper
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Gilbert
authors.forename: Michael P
authors.initials: MP
authors.lastname: Fay
authors.forename: Carole A
authors.initials: CA
authors.lastname: Long
authors.forename: Daming
authors.initials: D
authors.lastname: Zhu
authors.forename: Yimin
authors.initials: Y
authors.lastname: Wu
authors.forename: Laura B
authors.initials: LB
authors.lastname: Martin
authors.forename: Charles F
authors.initials: CF
authors.lastname: Anderson
authors.forename: Alison M
authors.initials: AM
authors.lastname: Lawrie
authors.forename: Adrian V S
authors.initials: AV
authors.lastname: Hill
authors.forename: Ruth D
authors.initials: RD
authors.lastname: Ellis
mesh_terms: D000276:Adjuvants, Immunologic / Q000009:adverse effects; D000293:Adolescent; D000328:Adult; D000536:Aluminum Hydroxide / Q000276:immunology; D000906:Antibodies / Q000276:immunology; D000953:Antigens, Protozoan / Q000276:immunology; D005260:Female; D006801:Humans; D008288:Malaria / Q000469:parasitology* / Q000517:prevention & control*; D017780:Malaria Vaccines / Q000009:adverse effects / Q000276:immunology*; D008297:Male; D008565:Membrane Proteins / Q000276:immunology; D008875:Middle Aged; D009838:Oligodeoxyribonucleotides / Q000276:immunology; D010963:Plasmodium falciparum / Q000254:growth & development* / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology; D014611:Vaccination / Q000009:adverse effects / Q000379:methods*; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D000906:Antibodies; D000953:Antigens, Protozoan; D017780:Malaria Vaccines; D008565:Membrane Proteins; D009838:Oligodeoxyribonucleotides; C483020:ProMune; D015800:Protozoan Proteins; C090077:apical membrane antigen I, Plasmodium; D000536:Aluminum Hydroxide