title: Non-propagating, recombinant vesicular stomatitis virus vectors encoding respiratory syncytial virus proteins generate potent humoral and cellular immunity against RSV and are protective in mice.
abstract: Respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract illness in infants, the elderly, and other high-risk individuals. Despite years of research in this field, there is no effective licensed vaccine to prevent RSV infection. We have generated candidate RSV vaccines using a recombinant vesicular stomatitis virus (rVSV) replicon in which the attachment and fusion domains of the VSV glycoprotein (G) have been deleted (rVSV-Gstem), rendering the virus propagation-defective except in the presence of complementing VSV G provided in trans. A form of this vector encoding the RSV fusion protein (F) gene expressed high levels of F in vitro and elicited durable neutralizing antibody responses as well as complete protection against RSV challenge in vivo. Mice vaccinated with rVSV-Gstem-RSV-F replicons also developed robust cellular responses characterized by both primary and memory Th1-biased CD8+ and CD4+ T cells. Furthermore, a single high dose of the Gstem-RSV-F replicon was effective against challenge with both RSV A and B subgroup viruses. Finally, addition of an RSV glycoprotein (G)-expressing Gstem vector significantly improved the incomplete protection achieved with a single low dose of Gstem-RSV-F vector alone.
authors.affiliation: Pfizer Vaccine Research, 401 North Middletown Road, Pearl River, NY 10965, USA. erik.johnson@pfizer.com
authors.forename: J Erik
authors.initials: JE
authors.lastname: Johnson
authors.forename: Lisa K
authors.initials: LK
authors.lastname: McNeil
authors.forename: Shakuntala
authors.initials: S
authors.lastname: Megati
authors.forename: Susan E
authors.initials: SE
authors.lastname: Witko
authors.forename: Vidia S
authors.initials: VS
authors.lastname: Roopchand
authors.forename: Jennifer H
authors.initials: JH
authors.lastname: Obregon
authors.forename: Deanne M
authors.initials: DM
authors.lastname: Illenberger
authors.forename: Cheryl S
authors.initials: CS
authors.lastname: Kotash
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Nowak
authors.forename: Emily
authors.initials: E
authors.lastname: Braunstein
authors.forename: Irene
authors.initials: I
authors.lastname: Yurgelonis
authors.forename: Kathrin U
authors.initials: KU
authors.lastname: Jansen
authors.forename: Narender K
authors.initials: NK
authors.lastname: Kalyan
authors.forename: Maninder K
authors.initials: MK
authors.lastname: Sidhu
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D023061:Gene Order; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007114:Immunization; D007156:Immunologic Memory; D051379:Mice; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000517:prevention & control; D012136:Respiratory Syncytial Viruses / Q000235:genetics* / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018116:Vesiculovirus / Q000235:genetics*; D014760:Viral Fusion Proteins / Q000235:genetics / Q000276:immunology
chemical_list: C526850:F protein, human respiratory syncytial virus; D014760:Viral Fusion Proteins