Peptide Nanoparticles as Novel Immunogens: Design and Analysis of a Prototypic Severe Acute Respiratory Syndrome Vaccine

• Published in: Chemical biology & drug design 2009-01, Vol.73 (1), p.53-61
• Main Authors: Pimentel, Tais A.P.F, Yan, Zhe, Jeffers, Scott A, Holmes, Kathryn V, Hodges, Robert S, Burkhard, Peter
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Antibodies - immunology; coiled-coils; Enzyme-Linked Immunosorbent Assay - methods; Epitopes - chemistry; Epitopes - immunology; Humans; Mice; Mice, Inbred BALB C; Models, Molecular; Molecular Sequence Data; Nanoparticles - chemistry; Nanoparticles - ultrastructure; peptide nanoparticles; Peptides - chemistry; Peptides - genetics; Peptides - immunology; Protein Conformation; protein design; Protein Subunits - chemistry; Protein Subunits - immunology; Recombinant Fusion Proteins - chemistry; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - metabolism; repetitive antigen display; SARS coronavirus; SARS spike glycoprotein; SARS Virus - immunology; Sequence Homology, Amino Acid; Severe Acute Respiratory Syndrome - immunology; Severe Acute Respiratory Syndrome - prevention & control; subunit vaccines; Vaccines - chemistry; Vaccines - immunology
• ISSN: 1747-0277; 1747-0285
• DOI: 10.1111/j.1747-0285.2008.00746.x

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 α-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.