A shared N-terminal hydrophobic tail for the formation of nanoparticulates

Nanomedicine (Lond). 2016 Sep;11(17):2289-303. doi: 10.2217/nnm-2016-0146. Epub 2016 Aug 8.

Abstract

Aim: Nanoparticulate design is important for the production of nanotechnological materials and passive immunogens. Using lessons from our hepatitis E vaccine, we herein design protein-based nanoparticles through incorporation of an N-terminal hydrophobic tail (NHT, located on HEV ORF2 aa368-460).

Materials & methods: Flu HA1, HIV gp41/gp120/p24, HBsAg and HPV16 L2 were fused with NHT, expressed in Escherichia coli and subjected to self-assembly in vitro. Nanosized particles were characterized by size-exclusion chromatography and negative electron microscopy. Immunogenicity was assessed in mice.

Results: All the NHT-fused proteins spontaneously formed nanoparticulates and presented with immunogenicity approximately 2-log over their nonassembling forms.

Conclusion: Protein self-assembly provides an attractive means to create nanosized particles that bear specific antigens. Our strategy outlines a novel and shared method for the design of immunogenic nanoparticles.

Keywords: hydrophobic tail; immunogenicity; particulate formation; protein-based nanoparticle; vaccine design.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Hepatitis E / prevention & control
  • Hydrophobic and Hydrophilic Interactions
  • Immunization
  • Mice
  • Mice, Inbred BALB C
  • Models, Molecular
  • Nanoparticles / chemistry*
  • Nanoparticles / ultrastructure
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / immunology
  • Viral Proteins / chemistry*
  • Viral Proteins / immunology
  • Viral Vaccines / chemistry*
  • Viral Vaccines / immunology
  • Virus Diseases / immunology
  • Virus Diseases / prevention & control*
  • Viruses / chemistry*
  • Viruses / immunology

Substances

  • ORF2 protein, Hepatitis E virus
  • Recombinant Fusion Proteins
  • Viral Proteins
  • Viral Vaccines