Chimeric hepatitis B virus core particles carrying an epitope of anthrax protective antigen induce protective immunity against Bacillus anthracis

Vaccine. 2008 Oct 29;26(46):5814-21. doi: 10.1016/j.vaccine.2008.08.031. Epub 2008 Sep 9.

Abstract

The major aim of present study is to develop and evaluate chimeric virus-like particles (VLPs) displaying a neutralizing epitope of anthrax protective antigen (PA) as a potential vaccine against anthrax. The truncated hepatitis B virus core (HBc) protein (aa 1-144) was used as a carrier, and the 2beta2-2beta3 loop of the PA domain 2 (aa 302-325) which has been shown contains a dominant neutralizing epitope was inserted into the major immunodominant region (MIR) of the HBc. The recombinant protein HBc-N144-PA-loop2 was expressed in Escherichia coli, and was able to form HBc-like particles confirmed by electron microscopy. The immunogenicity of these chimeric particles was evaluated in mice and guinea pigs. In mice the HBc-N144-PA-loop2 was able to induce PA-epitope specific antibodies; in guinea pigs it was able to induce PA-epitope specific antibodies and anthrax toxin-neutralizing antibodies regardless of whether alum adjuvant was used or not, and was able to partially protect the immunized guinea pigs against virulent anthrax spores challenge. This study suggests chimeric HBc particles carrying a neutralizing epitope of PA can induce protective immunity against Bacillus anthracis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / pharmacology
  • Alum Compounds
  • Animals
  • Anthrax / immunology
  • Anthrax / prevention & control*
  • Anthrax Vaccines / immunology*
  • Bacillus anthracis / immunology*
  • Bacillus anthracis / pathogenicity
  • Blotting, Western
  • Electrophoresis, Polyacrylamide Gel
  • Enzyme-Linked Immunosorbent Assay
  • Epitopes / immunology*
  • Female
  • Guinea Pigs
  • Hepatitis B Core Antigens / immunology*
  • Hepatitis B virus / ultrastructure
  • Mice
  • Mice, Inbred BALB C
  • Microscopy, Electron
  • Mutant Chimeric Proteins / immunology*
  • Neutralization Tests
  • Plasmids
  • Reverse Transcriptase Polymerase Chain Reaction
  • Spores, Bacterial / immunology
  • Spores, Bacterial / pathogenicity
  • Vaccines, Synthetic / immunology
  • Viral Fusion Proteins / immunology

Substances

  • Adjuvants, Immunologic
  • Alum Compounds
  • Anthrax Vaccines
  • Epitopes
  • Hepatitis B Core Antigens
  • Mutant Chimeric Proteins
  • Vaccines, Synthetic
  • Viral Fusion Proteins
  • aluminum sulfate