Phase 1 trial of AMA1-C1/Alhydrogel plus CPG 7909: an asexual blood-stage vaccine for Plasmodium falciparum malaria

PLoS One. 2008 Aug 13;3(8):e2940. doi: 10.1371/journal.pone.0002940.


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.

Conclusion/significance: 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.

Trial registration: NCT00344539.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aluminum Hydroxide / toxicity
  • Animals
  • Antigens, Protozoan / immunology*
  • Antigens, Protozoan / toxicity
  • Humans
  • Malaria Vaccines / toxicity*
  • Malaria, Falciparum / immunology*
  • Membrane Proteins / immunology
  • Membrane Proteins / toxicity
  • Middle Aged
  • Oligodeoxyribonucleotides / toxicity
  • Plasmodium falciparum / immunology*
  • Protozoan Proteins / immunology
  • Protozoan Proteins / toxicity
  • Safety


  • Antigens, Protozoan
  • Malaria Vaccines
  • Membrane Proteins
  • Oligodeoxyribonucleotides
  • ProMune
  • Protozoan Proteins
  • apical membrane antigen I, Plasmodium
  • Aluminum Hydroxide

Associated data