title: Safety and immunogenicity of mammalian cell derived and Modified Vaccinia Ankara vectored African swine fever subunit antigens in swine.
abstract: A reverse vaccinology system, Vaxign, was used to identify and select a subset of five African Swine Fever (ASF) antigens that were successfully purified from human embryonic kidney 293 (HEK) cells and produced in Modified vaccinia virus Ankara (MVA) viral vectors. Three HEK-purified antigens [B646L (p72), E183L (p54), and O61R (p12)], and three MVA-vectored antigens [B646L, EP153R, and EP402R (CD2v)] were evaluated using a prime-boost immunization regimen swine safety and immunogenicity study. Antibody responses were detected in pigs following prime-boost immunization four weeks apart with the HEK-293-purified p72, p54, and p12 antigens. Notably, sera from the vaccinees were positive by immunofluorescence on ASFV (Georgia 2007/1)-infected primary macrophages. Although MVA-vectored p72, CD2v, and EP153R failed to induce antibody responses, interferon-gamma (IFN-γ+) spot forming cell responses against all three antigens were detected one week post-boost. The highest IFN-γ+spot forming cell responses were detected against p72 in pigs primed with MVA-p72 and boosted with the recombinant p72. Antigen-specific (p12, p72, CD2v, and EP153R) T-cell proliferative responses were also detected post-boost. Collectively, these results are the first demonstration that ASFV subunit antigens purified from mammalian cells or expressed in MVA vectors are safe and can induce ASFV-specific antibody and T-cell responses following a prime-boost immunization regimen in swine.
authors.affiliation: Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, 53706, United States. Electronic address: loperamadrid@wisc.edu.
authors.forename: Jaime
authors.initials: J
authors.lastname: Lopera-Madrid
authors.affiliation: Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, 53706, United States. Electronic address: osorio@svm.vetmed.wisc.edu.
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Osorio
authors.affiliation: Unit for Laboratory Animal Medicine, Department of Microbiology and Immunology, Center for Computational Medicine and Bioinformatics, and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI, 48109, United States. Electronic address: yongqunh@med.umich.edu.
authors.forename: Yongqun
authors.initials: Y
authors.lastname: He
authors.affiliation: Unit for Laboratory Animal Medicine, Department of Microbiology and Immunology, Center for Computational Medicine and Bioinformatics, and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI, 48109, United States. Electronic address: xiangzsh@gmail.com.
authors.forename: Zuoshuang
authors.initials: Z
authors.lastname: Xiang
authors.affiliation: Department of Veterinary Pathobiology, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX, 77843-4467, United States. Electronic address: GADAMS@cvm.tamu.edu.
authors.forename: L Garry
authors.initials: LG
authors.lastname: Adams
authors.affiliation: Department of Veterinary Pathobiology, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX, 77843-4467, United States. Electronic address: richard.laughlin@tamuk.edu.
authors.forename: Richard C
authors.initials: RC
authors.lastname: Laughlin
authors.affiliation: Department of Veterinary Pathobiology, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX, 77843-4467, United States. Electronic address: wmwangi@vet.k-state.edu.
authors.forename: Waithaka
authors.initials: W
authors.lastname: Mwangi
authors.affiliation: Bioo Scientific Corporation, 7050 Burleson Rd., Austin, TX, 78744, United States. Electronic address: sandeshs@biooscientific.com.
authors.forename: Sandesh
authors.initials: S
authors.lastname: Subramanya
authors.affiliation: Plum Island Animal Disease Center, U. S. Department of Homeland Security Science and Technology, Greenport, New York, United States. Electronic address: john.neilan@HQ.DHS.GOV.
authors.forename: John
authors.initials: J
authors.lastname: Neilan
authors.affiliation: Plum Island Animal Disease Center, U. S. Department of Homeland Security Science and Technology, Greenport, New York, United States. Electronic address: David.Brake@ST.DHS.GOV.
authors.forename: David
authors.initials: D
authors.lastname: Brake
authors.affiliation: Plum Island Animal Disease Center, U. S. Department of Homeland Security Science and Technology, Greenport, New York, United States. Electronic address: thomas.burrage@HQ.DHS.GOV.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Burrage
authors.affiliation: Life Sciences Institute, University of Michigan, Ann Arbor, MI, 48109, United States. Electronic address: wclayb@umich.edu.
authors.forename: William Clay
authors.initials: WC
authors.lastname: Brown
authors.affiliation: Institute for Infectious Animal Disease, 2501 Earl Rudder Hwy, Suite 701, College Station, TX, 77845, United States. Electronic address: Alfonso.Clavijo@inspection.gc.ca.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Clavijo
authors.affiliation: Texas A&M Veterinary Medical Diagnostic Laboratory,1 Sippel Rd., College Station, TX, 77843, United States. Electronic address: mbounpheng@gmail.com.
authors.forename: Mangkey A
authors.initials: MA
authors.lastname: Bounpheng
mesh_terms: D000357:African Swine Fever / Q000276:immunology / Q000517:prevention & control*; D000358:African Swine Fever Virus / Q000235:genetics / Q000276:immunology*; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology*; D005822:Genetic Vectors; D016679:Genome, Viral; D057809:HEK293 Cells; D006801:Humans; D000071497:Immunogenicity, Vaccine; D008297:Male; D013552:Swine; D013601:T-Lymphocytes / Q000276:immunology; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D014614:Vaccines, Synthetic; D014765:Viral Vaccines
keywords: African swine fever virus; HEK-293; MVA; Recombinant protein expression; Reverse vaccinology; Vaccine development