Peptide nanoparticles as novel immunogens: design and analysis of a prototypic severe acute respiratory syndrome vaccine

Chem Biol Drug Des. 2009 Jan;73(1):53-61. doi: 10.1111/j.1747-0285.2008.00746.x.

Abstract

Severe acute respiratory syndrome (SARS) is an infectious disease caused by a novel coronavirus that cost nearly 800 lives. While there have been no recent outbreaks of the disease, the threat remains as SARS coronavirus (SARS-CoV) like strains still exist in animal reservoirs. Therefore, the development of a vaccine against SARS is in grave need. Here, we have designed and produced a prototypic SARS vaccine: a self-assembling polypeptide nanoparticle that repetitively displays a SARS B-cell epitope from the C-terminal heptad repeat of the virus' spike protein. Biophysical analyses with circular dichroism, transmission electron microscopy and dynamic light scattering confirmed the computational design showing alpha-helcial nanoparticles with sizes of about 25 nm. Immunization experiments with no adjuvants were performed with BALB/c mice. An investigation of the binding properties of the elicited antibodies showed that they were highly conformation specific for the coiled-coil epitope because they specifically recognized the native trimeric conformation of C-terminal heptad repeat region. Consequently, the antisera exhibited neutralization activity in an in vitro infection inhibition assay. We conclude that these peptide nanoparticles represent a promising platform for vaccine design, in particular for diseases that are characterized by neutralizing epitopes with coiled-coil conformation such as SARS-CoV or other enveloped viruses.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies / immunology
  • Enzyme-Linked Immunosorbent Assay / methods
  • Epitopes / chemistry
  • Epitopes / immunology
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Models, Molecular
  • Molecular Sequence Data
  • Nanoparticles* / chemistry
  • Nanoparticles* / ultrastructure
  • Peptides / chemistry*
  • Peptides / genetics
  • Peptides / immunology*
  • Protein Conformation
  • Protein Subunits / chemistry
  • Protein Subunits / immunology
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Severe Acute Respiratory Syndrome / immunology
  • Severe Acute Respiratory Syndrome / prevention & control*
  • Severe acute respiratory syndrome-related coronavirus / immunology*
  • Vaccines / chemistry
  • Vaccines / immunology*

Substances

  • Antibodies
  • Epitopes
  • Peptides
  • Protein Subunits
  • Recombinant Fusion Proteins
  • Vaccines