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A PRRSV GP5-Mosaic vaccine: Protection of pigs from challenge and ex vivo detection of IFNγ responses against several genotype 2 strains.

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.

SUBMITTER: Cui J

PROVIDER: S-EPMC6354972 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Simple Summary The gut microbiota could directly induce immune responses and affect the health of the host. In this study, we assessed changes in the gut microbiota of resistant segregated phenotypic pigs under Porcine Reproductive and Respiratory Syndrome Virus exposure. The results showed that the resistance of pigs was related to the composition of gut microbiota. The quantity and relative abundance of probiotics in resistant individuals positively affected host immunity and growth performance, whereas high levels of pathogenic bacteria in susceptible individuals were associated with poorer clinical outcomes. The results of this study suggest that gut microbiota may serve as an effective probiotic resource to provide new methods for PRRS prevention and treatment. Abstract Porcine Reproductive and Respiratory Syndrome (PRRS) is one of the serious infectious diseases that threatens the swine industry. Increasing evidence shows that gut microbiota plays an important role in regulating host immune responses to PRRS virus (PRRSV). The aim of this study was to investigate gut microbiota difference between PRRSV-resistant pigs and PRRSV-suspectable pigs derived from a Tongcheng pigs and Large White pigs crossed population. PRRSV infection induces an increase in the abundance and diversity of gut microbiota. Correlation analysis showed that 36 genera were correlated with viral loads or weight gain after PRRSV infection. Prevotellaceae-NK3B31-group, Christensenellaceae-R7-group, and Parabacteroides were highly correlated with both viral load and weight gain. Notably, the diversity and abundance of beneficial bacteria such as Prevotellaceae-NK3B31-group was high in resistant pigs, and the diversity and abundance of pathogenic bacteria such as Campylobacter and Desulfovibrio were high in susceptible pigs. Gut microbiota were significantly associated with immune function and growth performance, suggesting that these genera might be related to viremia, clinical symptoms, and disease resistance. Altogether, this study revealed the correlation of gut microbiota with PRRSV infection and gut microbiota interventions may provide an effective prevention against PRRSV infection.

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A PRRSV GP5-Mosaic vaccine: Protection of pigs from challenge and ex vivo detection of IFNγ responses against several genotype 2 strains.

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