Immunization of N terminus of enterovirus 71 VP4 elicits cross-protective antibody responses

BMC Microbiol. 2013 Dec 10:13:287. doi: 10.1186/1471-2180-13-287.

Abstract

Background: Enterovirus 71 (EV71) is major cause of hand, foot and mouth disease. Large epidemics of EV71 infection have been recently reported in the Asian-Pacific region. Currently, no vaccine is available to prevent EV71 infection.

Results: The peptide (VP4N20) consisting of the first 20 amino acids at the N-terminal of VP4 of EV71 genotype C4 were fused to hepatitis B core (HBcAg) protein. Expression of fusion proteins in E. coli resulted in the formation of chimeric virus-like particles (VLPs). Mice immunized with the chimeric VLPs elicited anti-VP4N20 antibody response. In vitro microneutralization experiments showed that anti-chimeric VLPs sera were able to neutralize not only EV71 of genotype C4 but also EV71 of genotype A. Neonatal mice model confirmed the neutralizing ability of anti-chimeric VLPs sera. Eiptope mapping led to the identification of a "core sequence" responsible for antibody recognition within the peptide.

Conclusions: Immunization of chimeric VLPs is able to elicit antibodies displaying a broad neutralizing activity against different genotypes of EV71 in vitro. The "core sequence" of EV71-VP4 is highly conserved across EV71 genotypes. The chimeric VLPs have a great potential to be a novel vaccine candidate with a broad cross-protection against different EV71 genotypes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Viral / blood
  • Cross Protection*
  • Cross Reactions
  • Disease Models, Animal
  • Enterovirus A, Human / genetics
  • Enterovirus A, Human / immunology*
  • Female
  • Hand, Foot and Mouth Disease / immunology
  • Hand, Foot and Mouth Disease / prevention & control*
  • Hepatitis B Core Antigens / genetics
  • Hepatitis B Core Antigens / immunology
  • Mice
  • Mice, Inbred BALB C
  • Neutralization Tests
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / immunology
  • Vaccines, Virus-Like Particle / administration & dosage
  • Vaccines, Virus-Like Particle / genetics
  • Vaccines, Virus-Like Particle / immunology*
  • Viral Proteins / genetics
  • Viral Proteins / immunology*
  • Viral Vaccines / administration & dosage
  • Viral Vaccines / genetics
  • Viral Vaccines / immunology*

Substances

  • Antibodies, Viral
  • Hepatitis B Core Antigens
  • Recombinant Fusion Proteins
  • Vaccines, Synthetic
  • Vaccines, Virus-Like Particle
  • Viral Proteins
  • Viral Vaccines