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

By Gale Smith, R. Raghunandan, Yingyun Wu, Ye V. Liu, M. Massare, Margret Nathan, Bin Zhou, Hanxin Lu, S. Boddapati, Jingning Li and 2 more. 2012

148 citations recorded by the source corpus.

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.

Subfields: Epidemiology, Infectious Diseases

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In Epidemiology

1. F. Sallusto
2. A. Lanzavecchia
3. D. Veesler

In Infectious Diseases

1. David Baker
2. D. Veesler

Citations in the corpus

• Induction of Potent Neutralizing Antibody Responses by a Designed Protein Nanoparticle Vaccine for Respiratory Syncytial Virus (2019, background): “Due to the relative instability of the prefusion conformation, subunit vaccine candidates were until recently limited to themore stable postfusion structure (McLellan et al., 2011; Smith et al., 2012; Swanson et al., 2011).”
• Self-assembling protein nanoparticles in the design of vaccines (2015, unknown): “In order to circumvent the fact that Abs others than the so-called broadly neutralizing antibodies (bNAbs) might occlude highly vulnerable HIV sites, Kwong and co-workers grafted a series of these HIV target motifs into different protein templates and the resultant chimeras were named ‘ supersite tr”