title: Vaccination with a heterologous respiratory syncytial virus chimeric FG glycoprotein demonstrates significant subgroup cross-reactivity.
abstract: A subunit vaccine candidate, termed FG, is a chimeric glycoprotein composed of the extracellular domains of the fusion (F) glycoprotein and the attachment (G) glycoproteins of a subgroup A respiratory syncytial virus (RSV). Two subgroups, A and B, of RSV differ primarily within the G glycoprotein. Therefore, it has been suggested that a subunit vaccine composed of the G glycoprotein would need to contain the G glycoproteins from both RSV subgroups. We have engineered a second chimeric glycoprotein, FGB, which is composed of the F glycoprotein from RSV subgroup A and the G glycoprotein from RSV subgroup B and is expressed in baculovirus. A comparison of protection between the two subunit vaccines (FG and FGB) was performed in cotton rats after homologous and heterologous virus challenge. FG and FGB appeared to afford the same degree of protection against either homologous or heterologous challenge. Serum neutralization titres against homologous or heterologous virus were nearly equivalent following FG or FGB vaccination. Radioimmunoprecipitation using sera from rats immunized with FG or FGB revealed cross-reactivity between the two G glycoproteins. Adsorption of anti-F antibody from serum of rats immunized with FG significantly reduced the RSV neutralizing activity of the serum suggesting that enhanced neutralization previously observed with FG antisera compared with F antisera alone may not be entirely attributed to antibodies against the G glycoprotein but may be attributed to a function associated with the G glycoprotein portion of FG which enhances the immunogenicity of the F portion of FG.
authors.affiliation: Cancer and Infectious Diseases Research, Upjohn Company, Kalamazoo, MI 49001.
authors.forename: N L
authors.initials: NL
authors.lastname: Oien
authors.forename: R J
authors.initials: RJ
authors.lastname: Brideau
authors.forename: D R
authors.initials: DR
authors.lastname: Thomsen
authors.forename: F L
authors.initials: FL
authors.lastname: Homa
authors.forename: M W
authors.initials: MW
authors.lastname: Wathen
mesh_terms: D000327:Adsorption; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D003001:Cloning, Molecular; D003429:Cross Reactions; D005260:Female; D015707:HN Protein; D008297:Male; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D016205:Sigmodontinae; D014611:Vaccination; D014759:Viral Envelope Proteins; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D015707:HN Protein; D011993:Recombinant Fusion Proteins; D014759:Viral Envelope Proteins; D014764:Viral Proteins; D014765:Viral Vaccines; C116204:attachment protein G