Novel 6xHis tagged foot-and-mouth disease virus vaccine bound to nanolipoprotein adjuvant via metal ions provides antigenic distinction and effective protective immunity

Virology. 2016 Aug:495:136-47. doi: 10.1016/j.virol.2016.04.027. Epub 2016 May 20.

Abstract

Here, we engineered two FMD viruses with histidine residues inserted into or fused to the FMDV capsid. Both 6xHis viruses exhibited growth kinetics, plaque morphologies and antigenic characteristics similar to wild-type virus. The 6xHis tag allowed one-step purification of the mutant virions by Co(2+) affinity columns. Electron microscopy and biochemical assays showed that the 6xHis FMDVs readily assembled into antigen: adjuvant complexes in solution, by conjugating with Ni(2+)-chelated nanolipoprotein and monophosphoryl lipid A adjuvant (MPLA:NiNLP). Animals Immunized with the inactivated 6xHis-FMDV:MPLA:NiNLP vaccine acquired enhanced protective immunity against FMDV challenge compared to virions alone. Induction of anti-6xHis and anti-FMDV neutralizing antibodies in the immunized animals could be exploited in the differentiation of vaccinated from infected animals needed for the improvement of FMD control measures. The novel marker vaccine/nanolipid technology described here has broad applications for the development of distinctive and effective immune responses to other pathogens of importance.

Keywords: 6xHis Tag; FMD vaccine; FMDV; Nanolipoprotein adjuvants.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adjuvants, Immunologic*
  • Animals
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / immunology
  • Antigens, Viral / immunology
  • Foot-and-Mouth Disease / immunology*
  • Foot-and-Mouth Disease / prevention & control*
  • Foot-and-Mouth Disease Virus / genetics
  • Foot-and-Mouth Disease Virus / immunology*
  • Gene Order
  • Genome, Viral
  • Ions*
  • Lipoproteins / immunology
  • Metals*
  • Models, Molecular
  • Mutation
  • Nanoparticles*
  • Protein Binding
  • Protein Conformation
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • Viral Vaccines / genetics
  • Viral Vaccines / immunology*

Substances

  • Adjuvants, Immunologic
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Antigens, Viral
  • Ions
  • Lipoproteins
  • Metals
  • Recombinant Fusion Proteins
  • Viral Vaccines