title: Induction of Robust Immune Responses in Swine by Using a Cocktail of Adenovirus-Vectored African Swine Fever Virus Antigens.
abstract: The African swine fever virus (ASFV) causes a fatal hemorrhagic disease in domestic swine, and at present no treatment or vaccine is available. Natural and gene-deleted, live attenuated strains protect against closely related virulent strains; however, they are yet to be deployed and evaluated in the field to rule out chronic persistence and a potential for reversion to virulence. Previous studies suggest that antibodies play a role in protection, but induction of cytotoxic T lymphocytes (CTLs) could be the key to complete protection. Hence, generation of an efficacious subunit vaccine depends on identification of CTL targets along with a suitable delivery method that will elicit effector CTLs capable of eliminating ASFV-infected host cells and confer long-term protection. To this end, we evaluated the safety and immunogenicity of an adenovirus-vectored ASFV (Ad-ASFV) multiantigen cocktail formulated in two different adjuvants and at two immunizing doses in swine. Immunization with the cocktail rapidly induced unprecedented ASFV antigen-specific antibody and cellular immune responses against all of the antigens. The robust antibody responses underwent rapid isotype switching within 1 week postpriming, steadily increased over a 2-month period, and underwent rapid recall upon boost. Importantly, the primed antibodies strongly recognized the parental ASFV (Georgia 2007/1) by indirect fluorescence antibody (IFA) assay and Western blotting. Significant antigen-specific gamma interferon-positive (IFN-γ+) responses were detected postpriming and postboosting. Furthermore, this study is the first to demonstrate induction of ASFV antigen-specific CTL responses in commercial swine using Ad-ASFV multiantigens. The relevance of the induced immune responses in regard to protection needs to be evaluated in a challenge study.
authors.affiliation: Department of Veterinary Pathobiology, Texas A&M University, College Station, Texas, USA SLokhandwala@cvm.tamu.edu WMwangi@cvm.tamu.edu.
authors.forename: Shehnaz
authors.identifier: http://orcid.org/0000-0002-0873-8611
authors.initials: S
authors.lastname: Lokhandwala
authors.affiliation: Department of Veterinary Pathobiology, Texas A&M University, College Station, Texas, USA.
authors.forename: Suryakant D
authors.initials: SD
authors.lastname: Waghela
authors.affiliation: Department of Veterinary Pathobiology, Texas A&M University, College Station, Texas, USA.
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Bray
authors.affiliation: Department of Veterinary Pathobiology, Texas A&M University, College Station, Texas, USA.
authors.forename: Cameron L
authors.initials: CL
authors.lastname: Martin
authors.affiliation: Department of Veterinary Pathobiology, Texas A&M University, College Station, Texas, USA.
authors.forename: Neha
authors.initials: N
authors.lastname: Sangewar
authors.affiliation: Department of Veterinary Pathobiology, Texas A&M University, College Station, Texas, USA.
authors.forename: Chloe
authors.initials: C
authors.lastname: Charendoff
authors.affiliation: Department of Veterinary Pathobiology, Texas A&M University, College Station, Texas, USA.
authors.forename: Rashmi
authors.initials: R
authors.lastname: Shetti
authors.affiliation: Department of Large Animal Clinical Sciences, Texas A&M University, College Station, Texas, USA.
authors.forename: Clay
authors.initials: C
authors.lastname: Ashley
authors.affiliation: Department of Poultry Science, Texas A&M University, College Station, Texas, USA.
authors.forename: Chang-Hsin
authors.initials: CH
authors.lastname: Chen
authors.affiliation: Department of Poultry Science, Texas A&M University, College Station, Texas, USA.
authors.forename: Luc R
authors.initials: LR
authors.lastname: Berghman
authors.affiliation: Zoetis, Kalamazoo, Michigan, USA.
authors.forename: Duncan
authors.initials: D
authors.lastname: Mwangi
authors.affiliation: Zoetis, Kalamazoo, Michigan, USA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Dominowski
authors.affiliation: Zoetis, Kalamazoo, Michigan, USA.
authors.forename: Dennis L
authors.initials: DL
authors.lastname: Foss
authors.affiliation: Zoetis, Kalamazoo, Michigan, USA.
authors.forename: Sharath
authors.initials: S
authors.lastname: Rai
authors.affiliation: Zoetis, Kalamazoo, Michigan, USA.
authors.forename: Shaunak
authors.initials: S
authors.lastname: Vora
authors.affiliation: Plum Island Animal Disease Center, U.S. Department of Homeland Security Science and Technology Directorate, Greenport, New York, USA.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Gabbert
authors.affiliation: Plum Island Animal Disease Center, U.S. Department of Homeland Security Science and Technology Directorate, Greenport, New York, USA.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Burrage
authors.affiliation: Plum Island Animal Disease Center, U.S. Department of Homeland Security Science and Technology Directorate, Greenport, New York, USA.
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 Directorate, Greenport, New York, USA.
authors.forename: John
authors.initials: J
authors.lastname: Neilan
authors.affiliation: Department of Veterinary Pathobiology, Texas A&M University, College Station, Texas, USA SLokhandwala@cvm.tamu.edu WMwangi@cvm.tamu.edu.
authors.forename: Waithaka
authors.initials: W
authors.lastname: Mwangi
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000358:African Swine Fever Virus / Q000276:immunology*; D000818:Animals; D000956:Antigens, Viral / Q000737:chemistry / Q000276:immunology*; D005822:Genetic Vectors; D007111:Immunity, Cellular; D000071497:Immunogenicity, Vaccine; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D013552:Swine; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D022223:Vaccines, Subunit / Q000009:adverse effects / Q000276:immunology; D014765:Viral Vaccines / Q000009:adverse effects / Q000276:immunology*; D014774:Virulence
chemical_list: D000956:Antigens, Viral; D022223:Vaccines, Subunit; D014765:Viral Vaccines; D007371:Interferon-gamma