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Development of a porcine reproductive and respiratory syndrome virus-like-particle-based vaccine and evaluation of its immunogenicity in pigs

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Abstract

Porcine reproductive and respiratory syndrome (PRRS) is a leading cause of economic burden to the pork industry worldwide. The routinely used modified live PRRS virus vaccine (PRRS-MLV) induces clinical protection, but it has safety concerns. Therefore, in an attempt to develop a safe and protective inactivated PRRSV vaccine, we generated PRRS-virus-like-particles (PRRS-VLPs) containing the viral surface proteins GP5-GP4-GP3-GP2a-M or GP5-M using a novel baculovirus expression system. Our in vitro results indicated that the desired PRRSV proteins were incorporated in both the VLPs preparations based on their reactivity in immunogold electron microscopy and ELISA. To boost their immunogenicity in pigs, we entrapped the PRRS-VLPs in PLGA nanoparticles and coadministered them intranasally with a potent adjuvant. We then evaluated their efficacy in pigs against a viral challenge using a virulent heterologous field isolate. Our results indicated that PRRS-VLPs induced an anamnestic immune response, since we observed boosted IgG and IFN-γ production in vaccinated and virus-challenged animals, but not during the pre-challenge period. Importantly, a two-log reduction in the lung viral load was detected in PRRS-VLP-vaccinated animals. In conclusion, we generated PRRS-VLPs containing up to five viral surface proteins and demonstrated their immunogenicity in pigs, but further studies are required to improve its immunogenicity and efficacy as a vaccine candidate.

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Acknowledgments

We acknowledge Dr. Quihong Wang for help in generating rBVs and VLPs. Drs. Fernando Osorio and Asit Patnaik (University of Nebraska Lincoln) and Mike Murtaugh (University of Minnesota) provided PRRSV reagents. Dr. Juliette Hanson provided help in animal studies. Mr. Suren R Gourapura edited the manuscript.

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Authors and Affiliations

  1. Food Animal Health Research Program (FAHRP), Ohio Agricultural Research and Development Center (OARDC), Department of Veterinary Preventive Medicine, College of Food Agriculture and Environmental Sciences, The Ohio State University, 1680 Madison Avenue, Wooster, OH, 44691, USA

    Basavaraj Binjawadagi, Yashavanth Shaan Lakshmanappa, Santosh Dhakal, Jagadish Hiremath, Kang Ouyang, Duan-Liang Shyu, Daral Jackwood & Gourapura J. Renukaradhya

  2. Department of Diagnostic Medicine and Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, 66506, USA

    Zhu Longchao, Shang Pengcheng & Ying Fang

  3. Department of Microbial Infection and Immunity, College of Medicine, The Ohio State University, Columbus, OH, 43210, USA

    Jesus Arcos & Jordi B. Torrelles

  4. Aptimmune Biologics Inc., Champaign, IL, 61820, USA

    Aaron Gilbertie

  5. Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Illinois, Urbana, IL, 61802, USA

    Federico Zuckermann

Authors
  1. Basavaraj Binjawadagi
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  2. Yashavanth Shaan Lakshmanappa
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  3. Zhu Longchao
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  4. Santosh Dhakal
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  5. Jagadish Hiremath
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  6. Kang Ouyang
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  7. Duan-Liang Shyu
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  8. Jesus Arcos
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  9. Shang Pengcheng
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  10. Aaron Gilbertie
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  11. Federico Zuckermann
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  12. Jordi B. Torrelles
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  13. Daral Jackwood
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  14. Ying Fang
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  15. Gourapura J. Renukaradhya
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Corresponding author

Correspondence to Gourapura J. Renukaradhya.

Ethics declarations

This study was funded by a National Pork Board (NPB# 09-213) award to GJR. Salaries and research support were provided by state and federal funds appropriated to OARDC.

Conflict of interest

All the authors declare no conflict of interest.

Ethics statement

This study was carried out in strict accordance with the recommendations of Public Health Service Policy, United States Department of Agriculture Regulations, the National Research Council’s Guide for the Care and Use of Laboratory Animals, and the Federation of Animal Science Societies’ Guide for the Care and Use of Agricultural Animals in Agricultural Research and Teaching; as well as all relevant institutional, state, and federal regulations and policies regarding animal care and use at The Ohio State University. The protocol was approved by the Committee on the Ethics of Animal Experiments of The Ohio State University (Protocol Number: 2012A00000109). During maintenance of pigs, sample collection, and euthanasia, all efforts were made to minimize suffering of pigs.

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Binjawadagi, B., Lakshmanappa, Y.S., Longchao, Z. et al. Development of a porcine reproductive and respiratory syndrome virus-like-particle-based vaccine and evaluation of its immunogenicity in pigs. Arch Virol 161, 1579–1589 (2016). https://doi.org/10.1007/s00705-016-2812-0

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  • DOI: https://doi.org/10.1007/s00705-016-2812-0

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