Abstract
Porcine reproductive and respiratory syndrome virus (PRRSV), is a highly mutable RNA virus that affects swine worldwide and its control is very challenging due to its formidable heterogeneity in the field. In the present study, DNA vaccines constructed with PRRSV GP5-Mosaic sequences were complexed to cationic liposomes and administered to experimental pigs by intradermal and intramuscular injection, followed by three boosters 14, 28 and 42 days later. The GP5-Mosaic vaccine thus formulated was immunogenic and induced protection from challenge in vaccinated pigs comparable to that induced by a wild type (VR2332) GP5 DNA vaccine (GP5-WT). Periodic sampling of blood and testing of vaccine-induced responses followed. Interferon-γ (IFN-γ) mRNA expression by virus-stimulated peripheral blood mononuclear cells (PBMCs) of GP5-Mosaic-vaccinated pigs was significantly higher compared to pigs vaccinated with either GP5-WT or empty vector at 21, 35 and 48 days after vaccination. Cross-reactive cellular responses were also demonstrated in GP5-Mosaic vaccinated pigs after stimulation of PBMCs with divergent strains of PRRSV. Thus, significantly higher levels of IFN-γ mRNA were detected when PBMCs from GP5-Mosaic-vaccinated pigs were stimulated by four Genotype 2 strains (VR2332, NADC9, NADC30 and SDSU73), which have at least 10% difference in GP5 amino acid sequences, while such responses were recorded only upon VR2332 stimulation in GP5-WT-vaccinated pigs. In addition, the levels of virus-specific neutralizing antibodies were higher in GP5-Mosaic or GP5-WT vaccinated pigs than those in vector-control pigs. The experimental pigs vaccinated with either the GP5-Mosaic vaccine or the GP5-WT vaccine were partially protected from challenge with VR2332, as measured by significantly lower viral loads in sera and tissues and lower lung lesion scores than the vector control group. These data demonstrate that the GP5-Mosaic vaccine can induce cross-reactive cellular responses to diverse strains, neutralizing antibodies, and protection in pigs.
Highlights
Porcine reproductive and respiratory syndrome (PRRS) is the most important infectious disease of swine worldwide, and is characterized by reproductive failure and respiratory disease [1,2]
The GP5 amino acid sequences of Mosaic 1 and Mosaic 2 of the GP5-Mosaic vaccine [35], NADC9, NADC30 and SDSU73 were of the same size and with no deletions or insertions, when compared to VR2332, the prototype of PRRS virus (PRRSV) genotype 2 (Fig 1A)
In order to address the extraordinary diversity of PRRSV, a GP5-Mosaic vaccine was developed in our laboratory and its soundness was confirmed in pigs [35]
Summary
Porcine reproductive and respiratory syndrome (PRRS) is the most important infectious disease of swine worldwide, and is characterized by reproductive failure and respiratory disease [1,2]. The disease causes a major negative economic impact in all major pork producing countries. The causative pathogen, PRRS virus (PRRSV), is a positive-sense, single-stranded enveloped RNA virus and is classified as a member of the genus Arterivirus, family Arteriviridae, order Nidovirales [4,5]. The viral genome is approximately 15 kb, and encodes 8 structural proteins and 14 non-structural proteins [6,7,8,9]. The main challenge with PRRSV is its great genetic and antigenic heterogeneity in the field. There are two main genotypes, Genotype 1 (European type) and Genotype 2 (North American type) [10], with up to 40% difference documented in the whole genome between genotypes, and up to 20% divergence within the same genotype [11]. The virus is highly immunomodulatory [12,13] which adds another layer of complexity in the efforts to control PRRS
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