Respiratory Syncytial Virus Fusion Glycoprotein Expressed in Insect Cells Form Protein Nanoparticles That Induce Protective Immunity in Cotton Rats

Gale Smith, Rama Raghunandan, Yingyun Wu, Ye Liu, Michael Massare, Margret Nathan, Bin Zhou, Hanxin Lu, Sarathi Boddapati, Jingning Li, David Flyer, Gregory Glenn

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article numbere50852
JournalPLoS One
Volume7
Issue number11
DOIs
StatePublished - Nov 30 2012
Externally publishedYes

Fingerprint

Sigmodon
Sigmodontinae
Respiratory Syncytial Viruses
nanoparticles
Viruses
Nanoparticles
Cotton
Insects
Rats
glycoproteins
Immunity
Glycoproteins
Fusion reactions
immunity
viruses
insects
Proteins
proteins
cells
Neutralizing Antibodies

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Respiratory Syncytial Virus Fusion Glycoprotein Expressed in Insect Cells Form Protein Nanoparticles That Induce Protective Immunity in Cotton Rats. / Smith, Gale; Raghunandan, Rama; Wu, Yingyun; Liu, Ye; Massare, Michael; Nathan, Margret; Zhou, Bin; Lu, Hanxin; Boddapati, Sarathi; Li, Jingning; Flyer, David; Glenn, Gregory.

In: PLoS One, Vol. 7, No. 11, e50852, 30.11.2012.

Research output: Contribution to journalArticle

Smith, G, Raghunandan, R, Wu, Y, Liu, Y, Massare, M, Nathan, M, Zhou, B, Lu, H, Boddapati, S, Li, J, Flyer, D & Glenn, G 2012, 'Respiratory Syncytial Virus Fusion Glycoprotein Expressed in Insect Cells Form Protein Nanoparticles That Induce Protective Immunity in Cotton Rats', PLoS One, vol. 7, no. 11, e50852. https://doi.org/10.1371/journal.pone.0050852
Smith, Gale ; Raghunandan, Rama ; Wu, Yingyun ; Liu, Ye ; Massare, Michael ; Nathan, Margret ; Zhou, Bin ; Lu, Hanxin ; Boddapati, Sarathi ; Li, Jingning ; Flyer, David ; Glenn, Gregory. / Respiratory Syncytial Virus Fusion Glycoprotein Expressed in Insect Cells Form Protein Nanoparticles That Induce Protective Immunity in Cotton Rats. In: PLoS One. 2012 ; Vol. 7, No. 11.
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