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

Identifieur interne : 001E28 ( Ncbi/Merge ); précédent : 001E27; suivant : 001E29

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

Auteurs : Tais A P F. Pimentel [États-Unis] ; Zhe Yan ; Scott A. Jeffers ; Kathryn V. Holmes ; Robert S. Hodges ; Peter Burkhard

Source :

RBID : pubmed:19152635

Descripteurs français

English descriptors

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.

DOI: 10.1111/j.1747-0285.2008.00746.x
PubMed: 19152635

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pubmed:19152635

Le document en format XML

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<div type="abstract" xml:lang="en">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.</div>
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