Safety and immunogenicity of a recombinant Plasmodium falciparum AMA1-DiCo malaria vaccine adjuvanted with GLA-SE or Alhydrogel® in European and African adults: A phase 1a/1b, randomized, double-blind multi-centre trial

Vaccine. 2017 Oct 27;35(45):6218-6227. doi: 10.1016/j.vaccine.2017.09.027. Epub 2017 Sep 22.

Abstract

Background: Plasmodium falciparum Apical Membrane Antigen 1 Diversity Covering (PfAMA1-DiCo) candidate vaccine is a formulation of three recombinant variants of AMA1 designed to provide broader protection against parasites with varying AMA1 sequences.

Methods: In this staggered phase Ia/Ib randomized, double blind trial, healthy French adults received AMA1-DiCo with either Alhydrogel® (n=15) or GLA-SE (n=15). Following a safety assessment in French volunteers, GLA-SE was chosen for the phase Ib trial where healthy Burkinabe adults received either AMA1-DiCo/GLA-SE (n=18) or placebo (n=18). AMA1-DiCo (50µg) was administered intramuscularly at baseline, Week 4 and 26.

Results: AMAI-DiCo was safe, well tolerated either with Alhydrogel® or GLA-SE. In European volunteers, the ratios of IgG increase from baseline were about 100 fold in Alhydrogel® group and 200-300 fold in GLA-SE group for the three antigens. In African volunteers, immunization resulted in IgG levels exceeding those observed for the European volunteers with a 4-fold increase. DiCo-specific IgG remained higher 26weeks after the third immunization than at baseline in both European and African volunteers. Induced antibodies were reactive against whole parasite derived from different strains.

Conclusion: AMA1-DiCo vaccine was safe and immunogenic whatever the adjuvant although GLA-SE appeared more potent than Alhydrogel® at inducing IgG responses.

Clinical trials registration: ClinicalTrials.gov NCT02014727; PACTR201402000719423.

Keywords: Adjuvants; Apical membrane antigen 1; Immunogenicity; Malaria; Plasmodium falciparum; Safety; Vaccine trial.

Publication types

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

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Adjuvants, Immunologic / adverse effects*
  • Adult
  • Africa
  • Antibodies, Protozoan / immunology
  • Antibody Formation / immunology
  • Antigens, Protozoan / immunology*
  • Double-Blind Method
  • Europe
  • Female
  • Humans
  • Immunization / adverse effects
  • Immunogenicity, Vaccine / immunology*
  • Immunoglobulin G / immunology
  • Malaria Vaccines / adverse effects*
  • Malaria Vaccines / immunology*
  • Malaria, Falciparum / immunology
  • Malaria, Falciparum / prevention & control
  • Male
  • Membrane Proteins / immunology*
  • Plasmodium falciparum / immunology*
  • Protozoan Proteins / immunology*
  • Recombinant Proteins / adverse effects
  • Recombinant Proteins / immunology
  • Young Adult

Substances

  • Adjuvants, Immunologic
  • Antibodies, Protozoan
  • Antigens, Protozoan
  • Immunoglobulin G
  • Malaria Vaccines
  • Membrane Proteins
  • Protozoan Proteins
  • Recombinant Proteins
  • apical membrane antigen I, Plasmodium

Associated data

  • PACTR/PACTR201402000719423
  • ClinicalTrials.gov/NCT02014727