Protective Efficacy of an Orf Virus-Vector Encoding the Hemagglutinin and the Nucleoprotein of Influenza A Virus in Swine

Swine influenza is a highly contagious respiratory disease of pigs caused by influenza A viruses (IAV-S). IAV-S causes significant economic losses to the swine industry and poses challenges to public health given its zoonotic potential. Thus effective IAV-S vaccines are needed and highly desirable a...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Lok R. Joshi, David Knudsen, Pablo Piñeyro, Santosh Dhakal, Gourapura J. Renukaradhya, Diego G. Diel
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	orf virus swine influenza virus vectored-vaccine neutralizing antibodies cell-mediated immunity Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/c3fc71d4de8548f4aa7f221115f5763b
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:c3fc71d4de8548f4aa7f221115f5763b
record_format	dspace
spelling	oai:doaj.org-article:c3fc71d4de8548f4aa7f221115f5763b2021-11-05T12:27:43ZProtective Efficacy of an Orf Virus-Vector Encoding the Hemagglutinin and the Nucleoprotein of Influenza A Virus in Swine1664-322410.3389/fimmu.2021.747574https://doaj.org/article/c3fc71d4de8548f4aa7f221115f5763b2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.747574/fullhttps://doaj.org/toc/1664-3224Swine influenza is a highly contagious respiratory disease of pigs caused by influenza A viruses (IAV-S). IAV-S causes significant economic losses to the swine industry and poses challenges to public health given its zoonotic potential. Thus effective IAV-S vaccines are needed and highly desirable and would benefit both animal and human health. Here, we developed two recombinant orf viruses, expressing the hemagglutinin (HA) gene (OV-HA) or the HA and the nucleoprotein (NP) genes of IAV-S (OV-HA-NP). The immunogenicity and protective efficacy of these two recombinant viruses were evaluated in pigs. Both OV-HA and OV-HA-NP recombinants elicited robust virus neutralizing antibody response in pigs, with higher levels of neutralizing antibodies (NA) being detected in OV-HA-NP-immunized animals pre-challenge infection. Although both recombinant viruses elicited IAV-S-specific T-cell responses, the frequency of IAV-S-specific proliferating CD8+ T cells upon re-stimulation was higher in OV-HA-NP-immunized animals than in the OV-HA group. Importantly, IgG1/IgG2 isotype ELISAs revealed that immunization with OV-HA induced Th2-biased immune responses, whereas immunization with OV-HA-NP virus resulted in a Th1-biased immune response. While pigs immunized with either OV-HA or OV-HA-NP were protected when compared to non-immunized controls, immunization with OV-HA-NP resulted in incremental protection against challenge infection as evidenced by a reduced secondary antibody response (NA and HI antibodies) following IAV-S challenge and reduced virus shedding in nasal secretions (lower viral RNA loads and frequency of animals shedding viral RNA and infectious virus), when compared to animals in the OV-HA group. Interestingly, broader cross neutralization activity was also observed in serum of OV-HA-NP-immunized animals against a panel of contemporary IAV-S isolates representing the major genetic clades circulating in swine. This study demonstrates the potential of ORFV-based vector for control of swine influenza virus in swine.Lok R. JoshiLok R. JoshiDavid KnudsenPablo PiñeyroSantosh DhakalGourapura J. RenukaradhyaDiego G. DielDiego G. DielFrontiers Media S.A.articleorf virusswine influenza virusvectored-vaccineneutralizing antibodiescell-mediated immunityImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	orf virus swine influenza virus vectored-vaccine neutralizing antibodies cell-mediated immunity Immunologic diseases. Allergy RC581-607
spellingShingle	orf virus swine influenza virus vectored-vaccine neutralizing antibodies cell-mediated immunity Immunologic diseases. Allergy RC581-607 Lok R. Joshi Lok R. Joshi David Knudsen Pablo Piñeyro Santosh Dhakal Gourapura J. Renukaradhya Diego G. Diel Diego G. Diel Protective Efficacy of an Orf Virus-Vector Encoding the Hemagglutinin and the Nucleoprotein of Influenza A Virus in Swine
description	Swine influenza is a highly contagious respiratory disease of pigs caused by influenza A viruses (IAV-S). IAV-S causes significant economic losses to the swine industry and poses challenges to public health given its zoonotic potential. Thus effective IAV-S vaccines are needed and highly desirable and would benefit both animal and human health. Here, we developed two recombinant orf viruses, expressing the hemagglutinin (HA) gene (OV-HA) or the HA and the nucleoprotein (NP) genes of IAV-S (OV-HA-NP). The immunogenicity and protective efficacy of these two recombinant viruses were evaluated in pigs. Both OV-HA and OV-HA-NP recombinants elicited robust virus neutralizing antibody response in pigs, with higher levels of neutralizing antibodies (NA) being detected in OV-HA-NP-immunized animals pre-challenge infection. Although both recombinant viruses elicited IAV-S-specific T-cell responses, the frequency of IAV-S-specific proliferating CD8+ T cells upon re-stimulation was higher in OV-HA-NP-immunized animals than in the OV-HA group. Importantly, IgG1/IgG2 isotype ELISAs revealed that immunization with OV-HA induced Th2-biased immune responses, whereas immunization with OV-HA-NP virus resulted in a Th1-biased immune response. While pigs immunized with either OV-HA or OV-HA-NP were protected when compared to non-immunized controls, immunization with OV-HA-NP resulted in incremental protection against challenge infection as evidenced by a reduced secondary antibody response (NA and HI antibodies) following IAV-S challenge and reduced virus shedding in nasal secretions (lower viral RNA loads and frequency of animals shedding viral RNA and infectious virus), when compared to animals in the OV-HA group. Interestingly, broader cross neutralization activity was also observed in serum of OV-HA-NP-immunized animals against a panel of contemporary IAV-S isolates representing the major genetic clades circulating in swine. This study demonstrates the potential of ORFV-based vector for control of swine influenza virus in swine.
format	article
author	Lok R. Joshi Lok R. Joshi David Knudsen Pablo Piñeyro Santosh Dhakal Gourapura J. Renukaradhya Diego G. Diel Diego G. Diel
author_facet	Lok R. Joshi Lok R. Joshi David Knudsen Pablo Piñeyro Santosh Dhakal Gourapura J. Renukaradhya Diego G. Diel Diego G. Diel
author_sort	Lok R. Joshi
title	Protective Efficacy of an Orf Virus-Vector Encoding the Hemagglutinin and the Nucleoprotein of Influenza A Virus in Swine
title_short	Protective Efficacy of an Orf Virus-Vector Encoding the Hemagglutinin and the Nucleoprotein of Influenza A Virus in Swine
title_full	Protective Efficacy of an Orf Virus-Vector Encoding the Hemagglutinin and the Nucleoprotein of Influenza A Virus in Swine
title_fullStr	Protective Efficacy of an Orf Virus-Vector Encoding the Hemagglutinin and the Nucleoprotein of Influenza A Virus in Swine
title_full_unstemmed	Protective Efficacy of an Orf Virus-Vector Encoding the Hemagglutinin and the Nucleoprotein of Influenza A Virus in Swine
title_sort	protective efficacy of an orf virus-vector encoding the hemagglutinin and the nucleoprotein of influenza a virus in swine
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/c3fc71d4de8548f4aa7f221115f5763b
work_keys_str_mv	AT lokrjoshi protectiveefficacyofanorfvirusvectorencodingthehemagglutininandthenucleoproteinofinfluenzaavirusinswine AT lokrjoshi protectiveefficacyofanorfvirusvectorencodingthehemagglutininandthenucleoproteinofinfluenzaavirusinswine AT davidknudsen protectiveefficacyofanorfvirusvectorencodingthehemagglutininandthenucleoproteinofinfluenzaavirusinswine AT pablopineyro protectiveefficacyofanorfvirusvectorencodingthehemagglutininandthenucleoproteinofinfluenzaavirusinswine AT santoshdhakal protectiveefficacyofanorfvirusvectorencodingthehemagglutininandthenucleoproteinofinfluenzaavirusinswine AT gourapurajrenukaradhya protectiveefficacyofanorfvirusvectorencodingthehemagglutininandthenucleoproteinofinfluenzaavirusinswine AT diegogdiel protectiveefficacyofanorfvirusvectorencodingthehemagglutininandthenucleoproteinofinfluenzaavirusinswine AT diegogdiel protectiveefficacyofanorfvirusvectorencodingthehemagglutininandthenucleoproteinofinfluenzaavirusinswine
_version_	1718444314015563776

Protective Efficacy of an Orf Virus-Vector Encoding the Hemagglutinin and the Nucleoprotein of Influenza A Virus in Swine

Ejemplares similares