Glutamate-rich protein (GLURP) induces antibodies that inhibit in vitro growth of Plasmodium falciparum in a phase 1 malaria vaccine trial

Vaccine. 2007 Apr 12;25(15):2930-40. doi: 10.1016/j.vaccine.2006.06.081. Epub 2006 Aug 2.

Abstract

The glutamate-rich protein (GLURP) of P. falciparum is the target of cytophilic antibodies which are significantly associated with protection against clinical malaria. A phase 1 clinical trial was conducted in healthy adult volunteers with the long synthetic peptide (LSP) GLURP(85-213) combined with either Aluminum Hydroxide (Alum, 18 volunteers) or Montanide ISA 720 (ISA, 18 volunteers) as adjuvants. Immunizations with 10, 30 or 100 microg GLURP(85-213) were administered subcutaneously at days 0, 30, and 120. Adverse events occurred more frequently with increasing dosage of GLURP(85-213) LSP and were more prevalent in the ISA group. Serious vaccine-related adverse events were not observed. The vaccine induced dose-dependent cellular and humoral immune responses, with high levels of (mainly cytophilic IgG1) antibodies that recognize parasites by immunofluorescence (IFA). Plasma samples collected 30 days after the last immunization induced a dose-dependent inhibition of parasite growth in vitro in the presence of monocytes. In conclusion, immunizations with GLURP(85-213) LSP formulations induce adverse events but can be administered safely, generating antibodies with capacity to mediate growth-inhibitory activity against P. falciparum in vitro.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Antibodies, Protozoan / biosynthesis*
  • Antibodies, Protozoan / immunology
  • Dose-Response Relationship, Immunologic
  • Female
  • Humans
  • Immunoglobulin G / biosynthesis
  • Immunoglobulin G / immunology
  • Malaria Vaccines / administration & dosage*
  • Malaria Vaccines / adverse effects
  • Malaria Vaccines / immunology
  • Malaria, Falciparum / immunology*
  • Malaria, Falciparum / parasitology
  • Malaria, Falciparum / prevention & control*
  • Male
  • Middle Aged
  • Neutrophils / immunology
  • Peptide Fragments / immunology
  • Plasmodium falciparum / growth & development
  • Plasmodium falciparum / immunology*
  • Protozoan Proteins / immunology*
  • Protozoan Proteins / metabolism

Substances

  • Antibodies, Protozoan
  • Immunoglobulin G
  • Malaria Vaccines
  • Peptide Fragments
  • Protozoan Proteins
  • glutamate-rich protein, Plasmodium