title: Multiple efficacy studies of an adenovirus-vectored foot-and-mouth disease virus serotype A24 subunit vaccine in cattle using homologous challenge.
abstract: The safety and efficacy of an experimental, replication-deficient, human adenovirus-vectored foot-and-mouth disease virus (FMDV) serotype A24 Cruzeiro capsid-based subunit vaccine (AdtA24) was examined in eight independent cattle studies. AdtA24 non-adjuvanted vaccine was administered intramuscularly to a total of 150 steers in doses ranging from approximately 1.0×10(8) to 2.1×10(11) particle units per animal. No detectable local or systemic reactions were observed after vaccination. At 7 days post-vaccination (dpv), vaccinated and control animals were challenged with FMDV serotype A24 Cruzeiro via the intradermal lingual route. Vaccine efficacy was measured by FMDV A24 serum neutralizing titers and by protection from clinical disease and viremia after challenge. The results of eight studies demonstrated a strong correlation between AdtA24 vaccine dose and protection from clinical disease (R(2)=0.97) and viremia (R(2)=0.98). There was also a strong correlation between FMDV A24 neutralization titers on day of challenge and protection from clinical disease (R(2)=0.99). Vaccination with AdtA24 enabled differentiation of infected from vaccinated animals (DIVA) as demonstrated by the absence of antibodies to the FMDV nonstructural proteins in vaccinates prior to challenge. Lack of AdtA24 vaccine shedding after vaccination was indicated by the absence of neutralizing antibody titers to both the adenovector and FMDV A24 Cruzeiro in control animals after co-mingling with vaccinated cattle for three to four weeks. In summary, a non-adjuvanted AdtA24 experimental vaccine was shown to be safe, immunogenic, consistently protected cattle at 7 dpv against direct, homologous FMDV challenge, and enabled differentiation of infected from vaccinated cattle prior to challenge.
authors.affiliation: Plum Island Animal Disease Center, U. S. Department of Homeland Security Science and Technology Directorate, P.O. Box 848, Greenport, NY 11944, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Schutta
authors.affiliation: The McConnell Group, Inc., Plum Island Animal Disease Center, P.O. Box 848, Greenport, NY 11944, USA.
authors.forename: José
authors.initials: J
authors.lastname: Barrera
authors.affiliation: The McConnell Group, Inc., Plum Island Animal Disease Center, P.O. Box 848, Greenport, NY 11944, USA; Oak Ridge Institute for Science and Education, PIADC Research Participation Program, Oak Ridge, TN, USA.
authors.forename: Melia
authors.initials: M
authors.lastname: Pisano
authors.affiliation: Plum Island Animal Disease Center, U. S. Department of Homeland Security Science and Technology Directorate, P.O. Box 848, Greenport, NY 11944, USA.
authors.forename: Laszlo
authors.initials: L
authors.lastname: Zsak
authors.affiliation: Plum Island Animal Disease Center, Foreign Animal Disease Research Unit, Agricultural Research Service, U. S. Department of Agriculture, P.O. Box 848, Greenport, NY 11944, USA.
authors.forename: Marvin J
authors.initials: MJ
authors.lastname: Grubman
authors.affiliation: Plum Island Animal Disease Center, Foreign Animal Disease Research Unit, Agricultural Research Service, U. S. Department of Agriculture, P.O. Box 848, Greenport, NY 11944, USA.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Mayr
authors.affiliation: Plum Island Animal Disease Center, Foreign Animal Disease Research Unit, Agricultural Research Service, U. S. Department of Agriculture, P.O. Box 848, Greenport, NY 11944, USA.
authors.forename: Mauro P
authors.initials: MP
authors.lastname: Moraes
authors.affiliation: Leidos, Inc., Plum Island Animal Disease Center, P.O. Box 848, Greenport, NY 11944, USA.
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Kamicker
authors.affiliation: Leidos, Inc., Plum Island Animal Disease Center, P.O. Box 848, Greenport, NY 11944, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Brake
authors.affiliation: GenVec, Inc., 910 Clopper Road, Suite 220N, Gaithersburg, MD 20878, USA.
authors.forename: Damodar
authors.initials: D
authors.lastname: Ettyreddy
authors.affiliation: GenVec, Inc., 910 Clopper Road, Suite 220N, Gaithersburg, MD 20878, USA.
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Brough
authors.affiliation: GenVec, Inc., 910 Clopper Road, Suite 220N, Gaithersburg, MD 20878, USA.
authors.forename: Bryan T
authors.initials: BT
authors.lastname: Butman
authors.affiliation: Plum Island Animal Disease Center, U. S. Department of Homeland Security Science and Technology Directorate, P.O. Box 848, Greenport, NY 11944, USA. Electronic address: john.neilan@st.dhs.gov.
authors.forename: John G
authors.initials: JG
authors.lastname: Neilan
mesh_terms: D000256:Adenoviridae; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D036022:Capsid Proteins / Q000276:immunology; D002417:Cattle; D002418:Cattle Diseases / Q000517:prevention & control* / Q000821:virology; D005536:Foot-and-Mouth Disease / Q000517:prevention & control*; D029544:Foot-and-Mouth Disease Virus; D008297:Male; D009500:Neutralization Tests; D065288:Serogroup; D022223:Vaccines, Subunit / Q000276:immunology; D017361:Viral Nonstructural Proteins / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology*; D017201:Virus Shedding
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D036022:Capsid Proteins; D022223:Vaccines, Subunit; D017361:Viral Nonstructural Proteins; D014765:Viral Vaccines
keywords: DIVA; FMDV serotype A24 Cruzeiro; Foot-and-mouth disease virus; Replication-deficient human adenovirus vectored vaccine; Vaccine efficacy