Cross-protective immunity to porcine reproductive and respiratory syndrome virus by intranasal delivery of a live virus vaccine with a potent adjuvant

Varun Dwivedi, Cordelia Manickam, Ruthi Patterson, Katie Dodson, Michael Murtaugh, Jordi B. Torrelles, Larry S. Schlesinger, Gourapura J. Renukaradhya

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

Porcine reproductive and respiratory syndrome (PRRS) is an immunosuppressive chronic respiratory viral disease of pigs that is responsible for major economic losses to the swine industry worldwide. The efficacy of parenteral administration of widely used modified live virus PRRS vaccine (PRRS-MLV) against genetically divergent PRRSV strains remains questionable. Therefore, we evaluated an alternate and proven mucosal immunization approach by intranasal delivery of PRRS-MLV (strain VR2332) with a potent adjuvant to elicit cross-protective immunity against a heterologous PRRSV (strain MN184). Mycobacterium tuberculosis whole cell lysate (Mtb WCL) was chosen as a potent mucosal adjuvant due to its Th1 biased immune response to PRRS-MLV. Unvaccinated pigs challenged with MN184 had clinical PRRS with severe lung pathology; however, vaccinated (PRRS-MLV+ Mtb WCL) pigs challenged with MN184 were apparently healthy. There was a significant increase in the body weight gain in vaccinated compared to unvaccinated PRRSV challenged pigs. Vaccinated compared to unvaccinated, virus-challenged pigs had reduced lung pathology associated with enhanced PRRSV neutralizing antibody titers and reduced viremia. Immunologically, an increased frequency of Th cells, Th/memory cells, γδ T cells, dendritic cells, and activated Th cells and a reduced frequency of T-regulatory cells were detected at both mucosal and systemic sites. Further, reduced secretion of immunosuppressive cytokines (IL-10 and TGF-β) and upregulation of the Th1 cytokine IFN-γ in blood and lungs were detected in mucosally vaccinated, PRRSV-challenged pigs. In conclusion, intranasal immunization of pigs with PRRS-MLV administered with Mtb WCL generated effective cross-protective immunity against PRRSV.

Original languageEnglish (US)
Pages (from-to)4058-4066
Number of pages9
JournalVaccine
Volume29
Issue number23
DOIs
StatePublished - May 23 2011

Bibliographical note

Funding Information:
This work was supported by a National Pork Board award (NPB #08-187 ) and a USDA-NIFA PRRS CAP2 award ( 2008-55620-19132 ) to RJG. Salaries and research support were provided by the state and federal funds appropriated to Ohio Agricultural Research and Development Center, The Ohio State University. We would like to thank Drs. Juliette Hanson, Mahesh Khatri, and Hadi Yassine, and Todd Root and Matthew Weeman for their help in animal studies. We would like to thank Drs. Eric Nelson, Mike Roof, Dobos, and Belisle for providing reagents. We also thank Bert Bishop for statistics, and Dr. Michele Williams for editing the manuscript.

Keywords

  • Cross-protection
  • Cytokines
  • Immune cells
  • M. tuberculosis whole cell lysate
  • Mucosal vaccination
  • Porcine reproductive and respiratory syndrome virus

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