Replication-competent or attenuated, nonpropagating vesicular stomatitis viruses expressing respiratory syncytial virus (RSV) antigens protect mice against RSV challenge.
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.
Kahn
J S
JS
Department of Pediatrics, Division of Infectious Diseases, Yale University School of Medicine, New Haven, Connecticut 06520, USA. jeffrey.kahn@yale.edu
Roberts
A
A
Weibel
C
C
Buonocore
L
L
Rose
J K
JK
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
D000956:Antigens, Viral; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic; D014764:Viral Proteins; D014765:Viral Vaccines