title: A nonproliferating parvovirus vaccine vector elicits sustained, protective humoral immunity following a single intravenous or intranasal inoculation.
abstract: An ideal vaccine delivery system would elicit persistent protection following a single administration, preferably by a noninvasive route, and be safe even in the face of immunosuppression, either inherited or acquired, of the recipient. We have exploited the unique life cycle of the autonomous parvoviruses to develop a nonproliferating vaccine platform that appears to both induce priming and continually boost a protective immune response following a single inoculation. A crippled parvovirus vector was constructed, based on a chimera between minute virus of mice (MVM) and LuIII, which expresses Borrelia burgdorferi outer surface protein A (OspA) instead of its coat protein. The vector was packaged into an MVM lymphotropic capsid and inoculated into naive C3H/HeNcr mice. Vaccination with a single vector dose, either intravenously or intranasally, elicited high-titer anti-OspA-specific antibody that provided protection from live spirochete challenge and was sustained over the lifetime of the animal. Both humoral and cell-mediated Th(1) immunity was induced, as shown by anti-OspA immunoglobulin G2a antibody and preferential gamma interferon production by OspA-specific CD4(+) T cells.
authors.affiliation: Department of Laboratory Medicine, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
authors.forename: Gene A
authors.initials: GA
authors.lastname: Palmer
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Brogdon
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Constant
authors.forename: Peter
authors.initials: P
authors.lastname: Tattersall
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood*; D000954:Antigens, Surface / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D001428:Bacterial Vaccines; D025065:Borrelia burgdorferi / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D005822:Genetic Vectors / Q000008:administration & dosage / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D007275:Injections, Intravenous; D008074:Lipoproteins; D008193:Lyme Disease / Q000276:immunology / Q000517:prevention & control; D022123:Lyme Disease Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008915:Minute Virus of Mice / Q000235:genetics* / Q000502:physiology; D017992:Parvovirus / Q000235:genetics* / Q000502:physiology; D011995:Recombination, Genetic
chemical_list: D000907:Antibodies, Bacterial; D000954:Antigens, Surface; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D008074:Lipoproteins; D022123:Lyme Disease Vaccines; C072045:OspA protein