Immunization with phage virus-like particles displaying Zika virus potential B-cell epitopes neutralizes Zika virus infection of monkey kidney cells

Vaccine. 2018 Feb 28;36(10):1256-1264. doi: 10.1016/j.vaccine.2018.01.056. Epub 2018 Feb 1.

Abstract

Zika virus (ZIKV) is a mosquito-borne flavivirus that has re-emerged and is associated with many debilitating clinical manifestations. Research is currently being conducted to develop a prophylactic vaccine against the virus; however, there has not been any licensed ZIKV vaccine. Recent studies have identified potential B-cell epitopes (amino acids 241-259, 294-315, 317-327, 346-361, 377-388 and 421-437) on the envelope protein of ZIKV, which could be explored to develop peptide vaccines against ZIKV infection. Nevertheless, the immunogenicity of these epitopes has never been assessed. Here, we displayed these epitopes on highly immunogenic bacteriophage virus-like particles (VLPs; MS2, PP7 and Qβ) platforms and assessed their immunogenicity in mice. Mice immunized with a mixture of VLPs displaying ZIKV envelope B-cell epitopes elicited anti-ZIKV antibodies. Although, immunized mice were not protected against a high challenge dose of ZIKV, sera - albeit at low titers - from immunized mice neutralized (in vitro) a low dose of ZIKV. Taken together, these results show that these epitopes are B-cell epitopes and they are immunogenic when displayed on a Qβ VLP platform. Furthermore, the results also show that immunization with VLPs displaying a single B-cell epitope minimally reduces ZIKV infection whereas immunization with a mixture of VLPs displaying a combination of the B-cell epitopes neutralizes ZIKV infection. Thus, immunization with a mixture of VLPs displaying multiple ZIKV B-cell epitopes is a good strategy to enhance ZIKV neutralization.

Keywords: B-cell epitopes; Bacteriophage virus-like particles; Neutralization; PRNT; Protection; Vaccine; Zika virus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / immunology*
  • Antibodies, Viral / immunology*
  • Bacteriophages / immunology*
  • Capsid Proteins / genetics
  • Capsid Proteins / immunology
  • Capsid Proteins / metabolism
  • Cell Line
  • Cell Surface Display Techniques*
  • Epitopes, B-Lymphocyte / genetics
  • Epitopes, B-Lymphocyte / immunology*
  • Haplorhini
  • Immunization
  • Immunogenicity, Vaccine
  • Mice
  • Neutralization Tests
  • Recombinant Proteins / genetics
  • Recombinant Proteins / immunology
  • Recombinant Proteins / metabolism
  • Vaccines, Virus-Like Particle / administration & dosage
  • Vaccines, Virus-Like Particle / immunology*
  • Vaccines, Virus-Like Particle / ultrastructure
  • Zika Virus / immunology*
  • Zika Virus / ultrastructure
  • Zika Virus Infection / immunology*
  • Zika Virus Infection / prevention & control

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Capsid Proteins
  • Epitopes, B-Lymphocyte
  • Recombinant Proteins
  • Vaccines, Virus-Like Particle