Respiratory Syncytial Virus Fusion Glycoprotein Expressed in Insect Cells Form Protein Nanoparticles That Induce Protective Immunity in Cotton Rats
| Autor: | Hanxin Lu, Bin Zhou, Gregory M. Glenn, Margret Nathan, Ye Liu, Sarathi Boddapati, Jingning Li, Yingyun Wu, Gale Smith, Michael J. Massare, Rama Raghunandan, David Flyer |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Male
Light viruses lcsh:Medicine Antibodies Viral Epitope Sf9 Cells Scattering Radiation lcsh:Science Lung Chromatography High Pressure Liquid Vaccines Multidisciplinary Cell fusion biology Immunogenicity Vaccination virus diseases respiratory system Respiratory Syncytial Viruses Medicine Antibody medicine.drug Research Article Palivizumab medicine.drug_class Respiratory Syncytial Virus Infections Monoclonal antibody Antibodies Monoclonal Humanized Microbiology Virus Virology Vaccine Development medicine Animals Humans Amino Acid Sequence Sigmodontinae Biology Glycoproteins lcsh:R Immunity Viral Vaccines Surface Plasmon Resonance Protein Structure Tertiary Disease Models Animal Viral replication biology.protein Nanoparticles lcsh:Q Clinical Immunology Mutant Proteins Viral Fusion Proteins |
| Zdroj: | PLoS ONE PLoS ONE, Vol 7, Iss 11, p e50852 (2012) |
| ISSN: | 1932-6203 |
| Popis: | Respiratory Syncytial Virus (RSV) is an important viral agent causing severe respiratory tract disease in infants and children as well as in the elderly and immunocompromised individuals. The lack of a safe and effective RSV vaccine represents a major unmet medical need. RSV fusion (F) surface glycoprotein was modified and cloned into a baculovirus vector for efficient expression in Sf9 insect cells. Recombinant RSV F was glycosylated and cleaved into covalently linked F2 and F1 polypeptides that formed homotrimers. RSV F extracted and purified from insect cell membranes assembled into 40 nm protein nanoparticles composed of multiple RSV F oligomers arranged in the form of rosettes. The immunogenicity and protective efficacy of purified RSV F nanoparticles was compared to live and formalin inactivated RSV in cotton rats. Immunized animals induced neutralizing serum antibodies, inhibited virus replication in the lungs, and had no signs of disease enhancement in the respiratory track of challenged animals. RSV F nanoparticles also induced IgG competitive for binding of palivizumab neutralizing monoclonal antibody to RSV F antigenic site II. Antibodies to this epitope are known to protect against RSV when passively administered in high risk infants. Together these data provide a rational for continued development a recombinant RSV F nanoparticle vaccine candidate. |
| Databáze: | OpenAIRE |
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