title: Replication-competent or attenuated, nonpropagating vesicular stomatitis viruses expressing respiratory syncytial virus (RSV) antigens protect mice against RSV challenge.
abstract: Foreign glycoproteins expressed in recombinant vesicular stomatitis virus (VSV) can elicit specific and protective immunity in the mouse model. We have previously demonstrated the expression of respiratory syncytial virus (RSV) G (attachment) and F (fusion) glycoprotein genes in recombinant VSV. In this study, we demonstrate the expression of RSV F and G glycoproteins in attenuated, nonpropagating VSVs which lack the VSV G gene (VSVDeltaG) and the incorporation of these RSV proteins into recombinant virions. We also show that intranasal vaccination of mice with nondefective VSV recombinants expressing RSV G (VSV-RSV G) or RSV F (VSV-RSV F) elicited RSV-specific antibodies in serum (by enzyme-linked immunosorbent assay [ELISA]) as well as neutralizing antibodies to RSV and afford complete protection against RSV challenge. In contrast, VSVDeltaG-RSV F induced detectable serum antibodies to RSV by ELISA, but no detectable neutralizing antibodies, yet it still protected from RSV challenge. VSVDeltaG-RSV G failed to induce any detectable serum (by ELISA) or neutralizing antibodies and failed to protect from RSV challenge. The attenuated, nonpropagating VSVDeltaG-RSV F is a particularly attractive candidate for a live attenuated recombinant RSV vaccine.
authors.affiliation: Department of Pediatrics, Division of Infectious Diseases, Yale University School of Medicine, New Haven, Connecticut 06520, USA. jeffrey.kahn@yale.edu
authors.forename: J S
authors.initials: JS
authors.lastname: Kahn
authors.forename: A
authors.initials: A
authors.lastname: Roberts
authors.forename: C
authors.initials: C
authors.lastname: Weibel
authors.forename: L
authors.initials: L
authors.lastname: Buonocore
authors.forename: J K
authors.initials: JK
authors.lastname: Rose
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000956:Antigens, Viral / Q000276:immunology*; D001483:Base Sequence; D002460:Cell Line; D006224:Cricetinae; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D018357:Respiratory Syncytial Virus Infections / Q000473:pathology / Q000517:prevention & control*; D014613:Vaccines, Attenuated / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology*; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics*; D014764:Viral Proteins / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology*; D014779:Virus Replication
chemical_list: D000956:Antigens, Viral; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic; D014764:Viral Proteins; D014765:Viral Vaccines