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Respiratory syncytial virus fusion glycoprotein expressed in insect cells form protein nanoparticles that induce protective immunity in cotton rats.
- Source :
-
PloS one [PLoS One] 2012; Vol. 7 (11), pp. e50852. Date of Electronic Publication: 2012 Nov 30. - Publication Year :
- 2012
-
Abstract
- 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.
- Subjects :
- Amino Acid Sequence
Animals
Antibodies, Monoclonal, Humanized immunology
Antibodies, Viral immunology
Chromatography, High Pressure Liquid
Disease Models, Animal
Humans
Light
Lung pathology
Lung virology
Male
Mutant Proteins chemistry
Mutant Proteins immunology
Nanoparticles ultrastructure
Palivizumab
Protein Structure, Tertiary
Respiratory Syncytial Virus Infections immunology
Scattering, Radiation
Sf9 Cells
Sigmodontinae virology
Surface Plasmon Resonance
Viral Fusion Proteins chemistry
Viral Fusion Proteins isolation & purification
Glycoproteins immunology
Immunity immunology
Nanoparticles chemistry
Respiratory Syncytial Virus Infections prevention & control
Respiratory Syncytial Viruses immunology
Sigmodontinae immunology
Viral Fusion Proteins immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 7
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 23226404
- Full Text :
- https://doi.org/10.1371/journal.pone.0050852