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Induction of Robust Immune Responses in Swine by Using a Cocktail of Adenovirus-Vectored African Swine Fever Virus Antigens

Induction of Robust Immune Responses in Swine by Using a Cocktail of Adenovirus-Vectored African... Induction of Robust Immune Responses in Swine by Using a Cocktail of Adenovirus-Vectored African Swine Fever Virus Antigens Shehnaz Lokhandwala a , Suryakant D. Waghela a , Jocelyn Bray a , Cameron L. Martin a , Neha Sangewar a , Chloe Charendoff a , Rashmi Shetti a , Clay Ashley b , Chang-Hsin Chen c * , Luc R. Berghman c , Duncan Mwangi d , Paul J. Dominowski d , Dennis L. Foss d , Sharath Rai d , Shaunak Vora d , Lindsay Gabbert e , Thomas G. Burrage e , David Brake e , John Neilan e and Waithaka Mwangi a a Department of Veterinary Pathobiology, Texas A&M University, College Station, Texas, USA b Department of Large Animal Clinical Sciences, Texas A&M University, College Station, Texas, USA c Department of Poultry Science, Texas A&M University, College Station, Texas, USA d Zoetis, Kalamazoo, Michigan, USA e Plum Island Animal Disease Center, U.S. Department of Homeland Security Science and Technology Directorate, Greenport, New York, USA D. W. Pascual , Editor University of Florida 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Clinical and Vaccine Immunology American Society For Microbiology

Induction of Robust Immune Responses in Swine by Using a Cocktail of Adenovirus-Vectored African Swine Fever Virus Antigens

Clinical and Vaccine Immunology , Volume 23 (11): 888 – Nov 1, 2016

Abstract

Induction of Robust Immune Responses in Swine by Using a Cocktail of Adenovirus-Vectored African Swine Fever Virus Antigens Shehnaz Lokhandwala a , Suryakant D. Waghela a , Jocelyn Bray a , Cameron L. Martin a , Neha Sangewar a , Chloe Charendoff a , Rashmi Shetti a , Clay Ashley b , Chang-Hsin Chen c * , Luc R. Berghman c , Duncan Mwangi d , Paul J. Dominowski d , Dennis L. Foss d , Sharath Rai d , Shaunak Vora d , Lindsay Gabbert e , Thomas G. Burrage e , David Brake e , John Neilan e and Waithaka Mwangi a a Department of Veterinary Pathobiology, Texas A&M University, College Station, Texas, USA b Department of Large Animal Clinical Sciences, Texas A&M University, College Station, Texas, USA c Department of Poultry Science, Texas A&M University, College Station, Texas, USA d Zoetis, Kalamazoo, Michigan, USA e Plum Island Animal Disease Center, U.S. Department of Homeland Security Science and Technology Directorate, Greenport, New York, USA D. W. Pascual , Editor University of Florida 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.

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References (42)

Publisher
American Society For Microbiology
Copyright
Copyright © 2016 by the American society for Microbiology.
ISSN
1556-6811
eISSN
1556-679X
DOI
10.1128/CVI.00395-16
pmid
27628166
Publisher site
See Article on Publisher Site

Abstract

Induction of Robust Immune Responses in Swine by Using a Cocktail of Adenovirus-Vectored African Swine Fever Virus Antigens Shehnaz Lokhandwala a , Suryakant D. Waghela a , Jocelyn Bray a , Cameron L. Martin a , Neha Sangewar a , Chloe Charendoff a , Rashmi Shetti a , Clay Ashley b , Chang-Hsin Chen c * , Luc R. Berghman c , Duncan Mwangi d , Paul J. Dominowski d , Dennis L. Foss d , Sharath Rai d , Shaunak Vora d , Lindsay Gabbert e , Thomas G. Burrage e , David Brake e , John Neilan e and Waithaka Mwangi a a Department of Veterinary Pathobiology, Texas A&M University, College Station, Texas, USA b Department of Large Animal Clinical Sciences, Texas A&M University, College Station, Texas, USA c Department of Poultry Science, Texas A&M University, College Station, Texas, USA d Zoetis, Kalamazoo, Michigan, USA e Plum Island Animal Disease Center, U.S. Department of Homeland Security Science and Technology Directorate, Greenport, New York, USA D. W. Pascual , Editor University of Florida 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.

Journal

Clinical and Vaccine ImmunologyAmerican Society For Microbiology

Published: Nov 1, 2016

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