title: Phase 1 trial of AMA1-C1/Alhydrogel plus CPG 7909: an asexual blood-stage vaccine for Plasmodium falciparum malaria.
abstract: BACKGROUND
  Apical Membrane Antigen 1 (AMA1), a polymorphic merozoite surface protein, is a leading blood-stage malaria vaccine candidate. This is the first reported use in humans of an investigational vaccine, AMA1-C1/Alhydrogel, with the novel adjuvant CPG 7909.
  
  
  METHODS
  A phase 1 trial was conducted at the University of Rochester with 75 malaria-naive volunteers to assess the safety and immunogenicity of the AMA1-C1/Alhydrogel+CPG 7909 malaria vaccine. Participants were sequentially enrolled and randomized within dose escalating cohorts to receive three vaccinations on days 0, 28 and 56 of either 20 microg of AMA1-C1/Alhydrogel+564 microg CPG 7909 (n = 15), 80 microg of AMA1-C1/Alhydrogel (n = 30), or 80 microg of AMA1-C1/Alhydrogel+564 microg CPG 7909 (n = 30).
  
  
  RESULTS
  Local and systemic adverse events were significantly more likely to be of higher severity with the addition of CPG 7909. Anti-AMA1 immunoglobulin G (IgG) were detected by enzyme-linked immunosorbent assay (ELISA), and the immune sera of volunteers that received 20 microg or 80 microg of AMA1-C1/Alhydrogel+CPG 7909 had up to 14 fold significant increases in anti-AMA1 antibody concentration compared to 80 microg of AMA1-C1/Alhydrogel alone. The addition of CPG 7909 to the AMA1-C1/Alhydrogel vaccine in humans also elicited AMA1 specific immune IgG that significantly and dramatically increased the in vitro growth inhibition of homologous parasites to levels as high as 96% inhibition.
  
  
  CONCLUSIONS
  The safety profile of the AMA1-C1/Alhydrogel+CPG 7909 malaria vaccine is acceptable, given the significant increase in immunogenicity observed. Further clinical development is ongoing.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00344539.
authors.affiliation: Malaria Vaccine Development Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America. greg.mullen@kcl.ac.uk
authors.forename: Gregory E D
authors.initials: GE
authors.lastname: Mullen
authors.forename: Ruth D
authors.initials: RD
authors.lastname: Ellis
authors.forename: Kazutoyo
authors.initials: K
authors.lastname: Miura
authors.forename: Elissa
authors.initials: E
authors.lastname: Malkin
authors.forename: Caroline
authors.initials: C
authors.lastname: Nolan
authors.forename: Mhorag
authors.initials: M
authors.lastname: Hay
authors.forename: Michael P
authors.initials: MP
authors.lastname: Fay
authors.forename: Allan
authors.initials: A
authors.lastname: Saul
authors.forename: Daming
authors.initials: D
authors.lastname: Zhu
authors.forename: Kelly
authors.initials: K
authors.lastname: Rausch
authors.forename: Samuel
authors.initials: S
authors.lastname: Moretz
authors.forename: Hong
authors.initials: H
authors.lastname: Zhou
authors.forename: Carole A
authors.initials: CA
authors.lastname: Long
authors.forename: Louis H
authors.initials: LH
authors.lastname: Miller
authors.forename: John
authors.initials: J
authors.lastname: Treanor
mesh_terms: D000293:Adolescent; D000328:Adult; D000536:Aluminum Hydroxide / Q000633:toxicity; D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology* / Q000633:toxicity; D006801:Humans; D017780:Malaria Vaccines / Q000633:toxicity*; D016778:Malaria, Falciparum / Q000276:immunology*; D008565:Membrane Proteins / Q000276:immunology / Q000633:toxicity; D008875:Middle Aged; D009838:Oligodeoxyribonucleotides / Q000633:toxicity; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology / Q000633:toxicity; D012449:Safety
chemical_list: 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