Peptide nanoparticles as novel immunogens: design and analysis of a prototypic severe acute respiratory syndrome vaccine.
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.
Pimentel
Tais A P F
TA
Institute of Materials Science, University of Connecticut, Storrs, CT 06269-3136, USA.
Yan
Zhe
Z
Jeffers
Scott A
SA
Holmes
Kathryn V
KV
Hodges
Robert S
RS
Burkhard
Peter
P
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D008969:Molecular Sequence Data; D053758:Nanoparticles / Q000737:chemistry / Q000648:ultrastructure; D010455:Peptides / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D011487:Protein Conformation; D021122:Protein Subunits / Q000737:chemistry / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D045473:Severe acute respiratory syndrome-related coronavirus / Q000276:immunology*; D017386:Sequence Homology, Amino Acid; D045169:Severe Acute Respiratory Syndrome / Q000276:immunology / Q000517:prevention & control*; D014612:Vaccines / Q000737:chemistry / Q000276:immunology*
D000906:Antibodies; D000939:Epitopes; D010455:Peptides; D021122:Protein Subunits; D011993:Recombinant Fusion Proteins; D014612:Vaccines