title: Mucosal delivery of human papillomavirus pseudovirus-encapsidated plasmids improves the potency of DNA vaccination.
abstract: Mucosal immunization may be important for protection against pathogens whose transmission and pathogenesis target the mucosal tissue. The capsid proteins of human papillomavirus (HPV) confer tropism for the basal epithelium and can encapsidate DNA during self-assembly to form pseudovirions (PsVs). Therefore, we produced mucosal vaccine vectors by HPV PsV encapsidation of DNA plasmids expressing an experimental antigen derived from the M and M2 proteins of respiratory syncytial virus (RSV). Intravaginal (IVag) delivery elicited local and systemic M-M2-specific CD8+ T-cell and antibody responses in mice that were comparable to an approximately 10,000-fold higher dose of naked DNA. A single HPV PsV IVag immunization primed for M-M2-specific-IgA in nasal and vaginal secretions. Based on light emission and immunofluorescent microscopy, immunization with HPV PsV-encapsidated luciferase- and red fluorescent protein (RFP)-expressing plasmids resulted in transient antigen expression (<5 days), which was restricted to the vaginal epithelium. HPV PsV encapsidation of plasmid DNA is a novel strategy for mucosal immunization that could provide new vaccine options for selected mucosal pathogens.
authors.affiliation: Viral Pathogenesis Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA. bgraham@nih.gov
authors.forename: B S
authors.initials: BS
authors.lastname: Graham
authors.forename: R C
authors.initials: RC
authors.lastname: Kines
authors.forename: K S
authors.initials: KS
authors.lastname: Corbett
authors.forename: J
authors.initials: J
authors.lastname: Nicewonger
authors.forename: T R
authors.initials: TR
authors.lastname: Johnson
authors.forename: M
authors.initials: M
authors.lastname: Chen
authors.forename: D
authors.initials: D
authors.lastname: LaVigne
authors.forename: J N
authors.initials: JN
authors.lastname: Roberts
authors.forename: N
authors.initials: N
authors.lastname: Cuburu
authors.forename: J T
authors.initials: JT
authors.lastname: Schiller
authors.forename: C B
authors.initials: CB
authors.lastname: Buck
mesh_terms: D000282:Administration, Intravaginal; D058956:Administration, Mucosal; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D004848:Epithelium / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000821:virology; D005260:Female; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D009092:Mucous Membrane / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000517:prevention & control / Q000635:transmission / Q000821:virology; D022261:Respiratory Syncytial Virus Vaccines; D012136:Respiratory Syncytial Viruses / Q000472:pathogenicity / Q000502:physiology*; D019444:Vaccines, DNA; D014621:Vagina / Q000473:pathology; D014763:Viral Matrix Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014771:Virion / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity
chemical_list: D007070:Immunoglobulin A; D022261:Respiratory Syncytial Virus Vaccines; D019444:Vaccines, DNA; D014763:Viral Matrix Proteins; D014764:Viral Proteins