title: Evaluation of a Fiber-Modified Adenovirus Vector Vaccine against Foot-and-Mouth Disease in Cattle.
abstract: Novel vaccination approaches against foot-and-mouth disease (FMD) include the use of replication-defective human adenovirus type 5 (Ad5) vectors that contain the capsid-encoding regions of FMD virus (FMDV). Ad5 containing serotype A24 capsid sequences (Ad5.A24) has proved to be effective as a vaccine against FMD in livestock species. However, Ad5-vectored FMDV serotype O1 Campos vaccine (Ad5.O1C.2B) provides only partial protection of cattle against homologous challenge. It has been reported that a fiber-modified Ad5 vector expressing Arg-Gly-Asp (RGD) enhances transduction of antigen-presenting cells (APC) in mice. In the current study, we assessed the efficacy of a fiber-modified Ad5 (Adt.O1C.2B.RGD) in cattle. Expression of FMDV capsid proteins was superior in cultured cells infected with the RGD-modified vector. Furthermore, transgene expression of Adt.O1C.2B.RGD was enhanced in cell lines that constitutively express integrin αvβ6, a known receptor for FMDV. In contrast, capsid expression in cattle-derived enriched APC populations was not enhanced by infection with this vector. Our data showed that vaccination with the two vectors yielded similar levels of protection against FMD in cattle. Although none of the vaccinated animals had detectable viremia, FMDV RNA was detected in serum samples from animals with clinical signs. Interestingly, CD4(+) and CD8(+) gamma interferon (IFN-γ)(+) cell responses were detected at significantly higher levels in animals vaccinated with Adt.O1C.2B.RGD than in animals vaccinated with Ad5.O1C.2B. Our results suggest that inclusion of an RGD motif in the fiber of Ad5-vectored FMD vaccine improves transgene delivery and cell-mediated immunity but does not significantly enhance vaccine performance in cattle.
authors.affiliation: Plum Island Animal Disease Center, Agricultural Research Service, U.S. Department of Agriculture, Northeast Area, Greenport, New York, USA.
authors.forename: Gisselle N
authors.initials: GN
authors.lastname: Medina
authors.affiliation: Plum Island Animal Disease Center, Agricultural Research Service, U.S. Department of Agriculture, Northeast Area, Greenport, New York, USA Oak Ridge Institute for Science and Education, Plum Island Animal Disease Center Research Participation Program, Oak Ridge, Tennessee, USA.
authors.forename: Nestor
authors.initials: N
authors.lastname: Montiel
authors.affiliation: Plum Island Animal Disease Center, Agricultural Research Service, U.S. Department of Agriculture, Northeast Area, Greenport, New York, USA.
authors.forename: Fayna
authors.initials: F
authors.lastname: Diaz-San Segundo
authors.affiliation: Plum Island Animal Disease Center, Agricultural Research Service, U.S. Department of Agriculture, Northeast Area, Greenport, New York, USA Oak Ridge Institute for Science and Education, Plum Island Animal Disease Center Research Participation Program, Oak Ridge, Tennessee, USA.
authors.forename: Diego
authors.initials: D
authors.lastname: Sturza
authors.affiliation: Plum Island Animal Disease Center, Agricultural Research Service, U.S. Department of Agriculture, Northeast Area, Greenport, New York, USA Oak Ridge Institute for Science and Education, Plum Island Animal Disease Center Research Participation Program, Oak Ridge, Tennessee, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Ramirez-Medina
authors.affiliation: Plum Island Animal Disease Center, Agricultural Research Service, U.S. Department of Agriculture, Northeast Area, Greenport, New York, USA.
authors.forename: Marvin J
authors.initials: MJ
authors.lastname: Grubman
authors.affiliation: Plum Island Animal Disease Center, Agricultural Research Service, U.S. Department of Agriculture, Northeast Area, Greenport, New York, USA teresa.delossantos@ars.usda.gov.
authors.forename: Teresa
authors.initials: T
authors.lastname: de los Santos
mesh_terms: D000260:Adenoviruses, Human / Q000235:genetics*; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000938:Antigen-Presenting Cells / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology*; D002417:Cattle; D002460:Cell Line; D005536:Foot-and-Mouth Disease / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D029544:Foot-and-Mouth Disease Virus / Q000276:immunology*; D005822:Genetic Vectors; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000276:immunology; D009842:Oligopeptides / Q000276:immunology; D012367:RNA, Viral / Q000097:blood; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D014766:Viremia
chemical_list: D000914:Antibodies, Viral; D036022:Capsid Proteins; D009842:Oligopeptides; D012367:RNA, Viral; D014614:Vaccines, Synthetic; D014765:Viral Vaccines; C047981:arginyl-glycyl-aspartic acid; D007371:Interferon-gamma