Phase I Safety and Immunogenicity Trial of FMP1/AS02A, a Plasmodium Falciparum MSP-1 Asexual Blood Stage Vaccine

Vaccine. 2006 Apr 5;24(15):3009-17. doi: 10.1016/j.vaccine.2005.11.028. Epub 2005 Nov 28.

Abstract

We report the first safety and immunogenicity trial of the Plasmodium falciparum malaria blood stage vaccine candidate, FMP1/AS02A consisting of the FMP1 antigen, an Escherichia coli-expressed His-tagged fusion protein from the 42 kDa C-terminal fragment from the 3D7 clone of the merozoite surface protein 1 formulated in the AS02A adjuvant. An open label, prospective, single-center Phase I dose escalation trial of FMP1/AS02A was conducted in 15 adult malaria-naïve human volunteers to assess safety, reactogenicity, and immunogenicity. The vaccine was safe and well-tolerated and no serious adverse events were observed. The vaccine induced high-titer ELISA and IFA responses in all volunteers. Proliferative and ELISPOT responses were induced to vaccine antigen. Biologically active antibodies were induced as measured by GIA. This study establishes the foundation to further evaluate and measure the vaccine's ability to reduce morbidity and mortality in target populations directly affected by P. falciparum malaria.

Publication types

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

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Adjuvants, Immunologic / pharmacology
  • Adolescent
  • Adult
  • Animals
  • Antibodies, Protozoan / blood
  • Drug Combinations
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Fluorescent Antibody Technique, Indirect
  • Humans
  • Interferon-gamma / biosynthesis
  • L-Lactate Dehydrogenase / analysis
  • Lipid A / administration & dosage
  • Lipid A / analogs & derivatives*
  • Lipid A / pharmacology
  • Malaria Vaccines / administration & dosage
  • Malaria Vaccines / adverse effects
  • Malaria Vaccines / immunology*
  • Male
  • Merozoite Surface Protein 1 / immunology*
  • Middle Aged
  • Plasmodium falciparum / growth & development
  • Plasmodium falciparum / immunology*
  • Saponins / administration & dosage
  • Saponins / pharmacology*
  • T-Lymphocytes / immunology
  • Vaccines, Subunit / administration & dosage
  • Vaccines, Subunit / adverse effects
  • Vaccines, Subunit / immunology
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / adverse effects
  • Vaccines, Synthetic / immunology

Substances

  • ASO2A adjuvant
  • Adjuvants, Immunologic
  • Antibodies, Protozoan
  • Drug Combinations
  • Lipid A
  • Malaria Vaccines
  • Merozoite Surface Protein 1
  • Saponins
  • Vaccines, Subunit
  • Vaccines, Synthetic
  • Interferon-gamma
  • L-Lactate Dehydrogenase