title: Protection against henipaviruses in swine requires both, cell-mediated and humoral immune response.
abstract: Hendra virus (HeV) and Nipah virus (NiV) are members of the genus Henipavirus, within the family Paramyxoviridae. Nipah virus has caused outbreaks of human disease in Bangladesh, Malaysia, Singapore, India and Philippines, in addition to a large outbreak in swine in Malaysia in 1998/1999. Recently, NiV was suspected to be a causative agent of an outbreak in horses in 2014 in the Philippines, while HeV has caused multiple human and equine outbreaks in Australia since 1994. A swine vaccine able to prevent shedding of infectious virus is of veterinary and human health importance, and correlates of protection against henipavirus infection in swine need to be better understood. In the present study, three groups of animals were employed. Pigs vaccinated with adjuvanted recombinant soluble HeV G protein (sGHEV) and challenged with HeV, developed antibody levels considered to be protective prior to the challenge (titers of 320). However, activation of the cell-mediated immune response was not detected, and the animals were only partially protected against challenge with 5×10(5) PFU of HeV per animal. In the second group, cross-neutralizing antibody levels against NiV in the sGHEV vaccinated animals did not reach protective levels, and with no activation of cellular immune memory, these animals were not protected against NiV. Only pigs orally infected with 5×10(4) PFU of NiV per animal were protected against nasal challenge with 5×10(5) PFU of NiV per animal. This group of pigs developed protective antibody levels, as well as cell-mediated immune memory. Peripheral blood mononuclear cells restimulated with UV-inactivated NiV upregulated IFN-gamma, IL-10 and the CD25 activation marker on CD4(+)CD8(+) T memory helper cells and to lesser extent on CD4(-)CD8(+) T cells. In conclusion, both humoral and cellular immune responses were required for protection of swine against henipaviruses.
authors.affiliation: National Centre for Foreign Animal Disease, Canadian Food Inspection Agency, Winnipeg, Manitoba, Canada; Department of Medical Microbiology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
authors.forename: Brad S
authors.initials: BS
authors.lastname: Pickering
authors.affiliation: Zoetis, Veterinary Medicine Research & Development, Kalamazoo, MI 49007, USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Hardham
authors.affiliation: National Centre for Foreign Animal Disease, Canadian Food Inspection Agency, Winnipeg, Manitoba, Canada.
authors.forename: Greg
authors.initials: G
authors.lastname: Smith
authors.affiliation: School of Public Health, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Eva T
authors.initials: ET
authors.lastname: Weingartl
authors.affiliation: Zoetis, Veterinary Medicine Research & Development, Kalamazoo, MI 49007, USA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Dominowski
authors.affiliation: Zoetis, Veterinary Medicine Research & Development, Kalamazoo, MI 49007, USA.
authors.forename: Dennis L
authors.initials: DL
authors.lastname: Foss
authors.affiliation: Zoetis, Veterinary Medicine Research & Development, Kalamazoo, MI 49007, USA.
authors.forename: Duncan
authors.initials: D
authors.lastname: Mwangi
authors.affiliation: Department of Microbiology and Immunology, Uniformed Services University, Bethesda, MD 20814, USA.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Broder
authors.affiliation: Center for Food Security and Public Health, College of Veterinary Medicine, Iowa State University, Ames, IA 50010, USA; Transboundary Animal Biologics, Inc, Ames, IA 50010, USA.
authors.forename: James A
authors.initials: JA
authors.lastname: Roth
authors.affiliation: National Centre for Foreign Animal Disease, Canadian Food Inspection Agency, Winnipeg, Manitoba, Canada; Department of Medical Microbiology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada. Electronic address: hana.weingartl@inspection.gc.ca.
authors.forename: Hana M
authors.initials: HM
authors.lastname: Weingartl
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D056738:Cross Protection; D045404:Hendra Virus; D045464:Henipavirus Infections / Q000276:immunology / Q000517:prevention & control*; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D009500:Neutralization Tests; D045405:Nipah Virus; D011994:Recombinant Proteins / Q000276:immunology; D013552:Swine / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology*; D017201:Virus Shedding
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D011994:Recombinant Proteins; D014765:Viral Vaccines; D016753:Interleukin-10; D007371:Interferon-gamma
keywords: Cell-mediated immune response; Hendra virus; Neutralizing antibody; Nipah virus; Swine