An innovative approach to induce cross-protective immunity against porcine reproductive and respiratory syndrome virus in the lungs of pigs through adjuvanted nanotechnology-based vaccination

Basavaraj Binjawadagi,1,2 Varun Dwivedi,1 Cordelia Manickam,1,2 Kang Ouyang,1 Jordi B Torrelles,3 Gourapura J Renukaradhya1,21Food Animal Health Research Program, Ohio Agricultural Research and Development Center, 2Department of Veterinary Preventive Medicine, The Ohio State University, Wooster, OH...

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Autores principales:	Binjawadagi B, Dwivedi V, Manickam C, Ouyang K, Torrelles JB, Renukaradhya GJ
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2014
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/c6424047938e4e6f947b02904f011243
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spelling	oai:doaj.org-article:c6424047938e4e6f947b02904f0112432021-12-02T00:22:13ZAn innovative approach to induce cross-protective immunity against porcine reproductive and respiratory syndrome virus in the lungs of pigs through adjuvanted nanotechnology-based vaccination1178-2013https://doaj.org/article/c6424047938e4e6f947b02904f0112432014-03-01T00:00:00Zhttp://www.dovepress.com/an-innovative-approach-to-induce-cross-protective-immunity-against-por-a16206https://doaj.org/toc/1178-2013 Basavaraj Binjawadagi,1,2 Varun Dwivedi,1 Cordelia Manickam,1,2 Kang Ouyang,1 Jordi B Torrelles,3 Gourapura J Renukaradhya1,21Food Animal Health Research Program, Ohio Agricultural Research and Development Center, 2Department of Veterinary Preventive Medicine, The Ohio State University, Wooster, OH, USA; 3Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH, USAAbstract: Porcine reproductive and respiratory syndrome (PRRS) is an economically devastating respiratory disease of pigs. The disease is caused by the PRRS virus (PRRSV), an Arterivirus which is a highly mutating RNA virus. Widely used modified live PRRSV vaccines have failed to prevent PRRS outbreaks and reinfections; moreover, safety of the live virus vaccines is questionable. Though poorly immunogenic, inactivated PRRSV vaccine is safe. The PRRSV infects primarily the lung macrophages. Therefore, we attempted to strengthen the immunogenicity of inactivated/killed PRRSV vaccine antigens (KAg), especially in the pig respiratory system, through: 1) entrapping the KAg in biodegradable poly(lactic-co-glycolic acid) nanoparticles (NP-KAg); 2) coupling the NP-KAg with a potent mucosal adjuvant, whole cell lysate of Mycobacterium tuberculosis (M. tb WCL); and 3) delivering the vaccine formulation twice intranasally to growing pigs. We have previously shown that a single dose of NP-KAg partially cleared the challenged heterologous PRRSV. Recently, we reported that NP-KAg coupled with unentrapped M. tb WCL significantly cleared the viremia of challenged heterologous PRRSV. Since PRRSV is primarily a lung disease, our goal in this study was to investigate lung viral load and various immune correlates of protection at the lung mucosal surfaces and its parenchyma in vaccinated heterologous PRRSV-challenged pigs. Our results indicated that out of five different vaccine-adjuvant formulations, the combination of NP-KAg and unentrapped M. tb WCL significantly cleared detectable replicating infective PRRSV with a tenfold reduction in viral RNA load in the lungs, associated with substantially reduced gross and microscopic lung pathology. Immunologically, strong humoral (enhanced virus neutralization titers by high avidity antibodies) and cell-mediated immune responses (augmented population of interferon-γ secreting CD4+ and CD8+ lymphocytes and reduced secretion of immunosuppressive cytokines) in the lungs were observed. In conclusion, combination of NP-KAg and soluble M. tb WCL elicits broadly cross-protective anti-PRRSV immunity in the pig respiratory system.Keywords: PRRSV, mucosal vaccine, PLGA nanoparticles, cross-protection, M. tb WCLBinjawadagi BDwivedi VManickam COuyang KTorrelles JBRenukaradhya GJDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2014, Iss Issue 1, Pp 1519-1535 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Binjawadagi B Dwivedi V Manickam C Ouyang K Torrelles JB Renukaradhya GJ An innovative approach to induce cross-protective immunity against porcine reproductive and respiratory syndrome virus in the lungs of pigs through adjuvanted nanotechnology-based vaccination
description	Basavaraj Binjawadagi,1,2 Varun Dwivedi,1 Cordelia Manickam,1,2 Kang Ouyang,1 Jordi B Torrelles,3 Gourapura J Renukaradhya1,21Food Animal Health Research Program, Ohio Agricultural Research and Development Center, 2Department of Veterinary Preventive Medicine, The Ohio State University, Wooster, OH, USA; 3Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH, USAAbstract: Porcine reproductive and respiratory syndrome (PRRS) is an economically devastating respiratory disease of pigs. The disease is caused by the PRRS virus (PRRSV), an Arterivirus which is a highly mutating RNA virus. Widely used modified live PRRSV vaccines have failed to prevent PRRS outbreaks and reinfections; moreover, safety of the live virus vaccines is questionable. Though poorly immunogenic, inactivated PRRSV vaccine is safe. The PRRSV infects primarily the lung macrophages. Therefore, we attempted to strengthen the immunogenicity of inactivated/killed PRRSV vaccine antigens (KAg), especially in the pig respiratory system, through: 1) entrapping the KAg in biodegradable poly(lactic-co-glycolic acid) nanoparticles (NP-KAg); 2) coupling the NP-KAg with a potent mucosal adjuvant, whole cell lysate of Mycobacterium tuberculosis (M. tb WCL); and 3) delivering the vaccine formulation twice intranasally to growing pigs. We have previously shown that a single dose of NP-KAg partially cleared the challenged heterologous PRRSV. Recently, we reported that NP-KAg coupled with unentrapped M. tb WCL significantly cleared the viremia of challenged heterologous PRRSV. Since PRRSV is primarily a lung disease, our goal in this study was to investigate lung viral load and various immune correlates of protection at the lung mucosal surfaces and its parenchyma in vaccinated heterologous PRRSV-challenged pigs. Our results indicated that out of five different vaccine-adjuvant formulations, the combination of NP-KAg and unentrapped M. tb WCL significantly cleared detectable replicating infective PRRSV with a tenfold reduction in viral RNA load in the lungs, associated with substantially reduced gross and microscopic lung pathology. Immunologically, strong humoral (enhanced virus neutralization titers by high avidity antibodies) and cell-mediated immune responses (augmented population of interferon-γ secreting CD4+ and CD8+ lymphocytes and reduced secretion of immunosuppressive cytokines) in the lungs were observed. In conclusion, combination of NP-KAg and soluble M. tb WCL elicits broadly cross-protective anti-PRRSV immunity in the pig respiratory system.Keywords: PRRSV, mucosal vaccine, PLGA nanoparticles, cross-protection, M. tb WCL
format	article
author	Binjawadagi B Dwivedi V Manickam C Ouyang K Torrelles JB Renukaradhya GJ
author_facet	Binjawadagi B Dwivedi V Manickam C Ouyang K Torrelles JB Renukaradhya GJ
author_sort	Binjawadagi B
title	An innovative approach to induce cross-protective immunity against porcine reproductive and respiratory syndrome virus in the lungs of pigs through adjuvanted nanotechnology-based vaccination
title_short	An innovative approach to induce cross-protective immunity against porcine reproductive and respiratory syndrome virus in the lungs of pigs through adjuvanted nanotechnology-based vaccination
title_full	An innovative approach to induce cross-protective immunity against porcine reproductive and respiratory syndrome virus in the lungs of pigs through adjuvanted nanotechnology-based vaccination
title_fullStr	An innovative approach to induce cross-protective immunity against porcine reproductive and respiratory syndrome virus in the lungs of pigs through adjuvanted nanotechnology-based vaccination
title_full_unstemmed	An innovative approach to induce cross-protective immunity against porcine reproductive and respiratory syndrome virus in the lungs of pigs through adjuvanted nanotechnology-based vaccination
title_sort	innovative approach to induce cross-protective immunity against porcine reproductive and respiratory syndrome virus in the lungs of pigs through adjuvanted nanotechnology-based vaccination
publisher	Dove Medical Press
publishDate	2014
url	https://doaj.org/article/c6424047938e4e6f947b02904f011243
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An innovative approach to induce cross-protective immunity against porcine reproductive and respiratory syndrome virus in the lungs of pigs through adjuvanted nanotechnology-based vaccination

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