1. Development of a porcine reproductive and respiratory syndrome virus-like-particle-based vaccine and evaluation of its immunogenicity in pigs.
- Author
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Binjawadagi B, Lakshmanappa YS, Longchao Z, Dhakal S, Hiremath J, Ouyang K, Shyu DL, Arcos J, Pengcheng S, Gilbertie A, Zuckermann F, Torrelles JB, Jackwood D, Fang Y, and Renukaradhya GJ
- Subjects
- Animals, Antibodies, Viral blood, Cell Line, Cytokines metabolism, Genes, Viral, Lung immunology, Lung virology, Porcine Reproductive and Respiratory Syndrome virology, Porcine respiratory and reproductive syndrome virus genetics, Sus scrofa, Swine, Vaccines, Inactivated genetics, Vaccines, Inactivated immunology, Vaccines, Virus-Like Particle genetics, Vaccines, Virus-Like Particle immunology, Viral Envelope Proteins genetics, Viral Envelope Proteins immunology, Viral Load, Viral Vaccines genetics, Porcine Reproductive and Respiratory Syndrome immunology, Porcine Reproductive and Respiratory Syndrome prevention & control, Porcine respiratory and reproductive syndrome virus immunology, Viral Vaccines immunology
- 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.
- Published
- 2016
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