Reduced Virus Load in Lungs of Pigs Challenged with Porcine Reproductive and Respiratory Syndrome Virus after Vaccination with Virus Replicon Particles Encoding Conserved PRRSV Cytotoxic T-Cell Epitopes

Porcine reproductive and respiratory syndrome virus (PRRSV) causes severe respiratory distress and reproductive failure in swine. Modified live virus (MLV) vaccines provide the highest degree of protection and are most often the preferred choice. While somewhat protective, the use of MLVs is accompa...

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Main Authors: Simon Welner, Nicolas Ruggli, Matthias Liniger, Artur Summerfield, Lars Erik Larsen, Gregers Jungersen
Format: Article
Language:English
Published: MDPI AG 2021-03-01
Series:Vaccines
Subjects:
Online Access:https://www.mdpi.com/2076-393X/9/3/208
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author Simon Welner
Nicolas Ruggli
Matthias Liniger
Artur Summerfield
Lars Erik Larsen
Gregers Jungersen
author_facet Simon Welner
Nicolas Ruggli
Matthias Liniger
Artur Summerfield
Lars Erik Larsen
Gregers Jungersen
author_sort Simon Welner
collection DOAJ
description Porcine reproductive and respiratory syndrome virus (PRRSV) causes severe respiratory distress and reproductive failure in swine. Modified live virus (MLV) vaccines provide the highest degree of protection and are most often the preferred choice. While somewhat protective, the use of MLVs is accompanied by multiple safety issues, why safer alternatives are urgently needed. Here, we describe the generation of virus replicon particles (VRPs) based on a classical swine fever virus genome incapable of producing infectious progeny and designed to express conserved PRRSV-2 cytotoxic T-cell epitopes. Eighteen pigs matched with the epitopes by their swine leucocyte antigen-profiles were vaccinated (N = 11, test group) or sham-vaccinated (N = 7, control group) with the VRPs and subsequently challenged with PRRSV-2. The responses to vaccination and challenge were monitored using serological, immunological, and virological analyses. Challenge virus load in serum did not differ significantly between the groups, whereas the virus load in the caudal part of the lung was significantly lower in the test group compared to the control group. The number of peptide-induced interferon-γ secreting cells after challenge was higher and more frequent in the test group than in the control group. Together, our results provide indications of a shapeable PRRSV-specific cell-mediated immune response that may inspire future development of effective PRRSV vaccines.
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spelling doaj.art-0a4b3e46ac7f4386955421839d1b0d7e2023-12-03T12:11:18ZengMDPI AGVaccines2076-393X2021-03-019320810.3390/vaccines9030208Reduced Virus Load in Lungs of Pigs Challenged with Porcine Reproductive and Respiratory Syndrome Virus after Vaccination with Virus Replicon Particles Encoding Conserved PRRSV Cytotoxic T-Cell EpitopesSimon Welner0Nicolas Ruggli1Matthias Liniger2Artur Summerfield3Lars Erik Larsen4Gregers Jungersen5Section for Veterinary Clinical Microbiology, Department of Veterinary and Animal Sciences, University of Copenhagen, Dyrlægevej 88, 1870 Frederiksberg C, DenmarkInstitute of Virology and Immunology IVI, Sensemattstrasse 293, 3147 Mittelhäusern, SwitzerlandInstitute of Virology and Immunology IVI, Sensemattstrasse 293, 3147 Mittelhäusern, SwitzerlandInstitute of Virology and Immunology IVI, Sensemattstrasse 293, 3147 Mittelhäusern, SwitzerlandSection for Veterinary Clinical Microbiology, Department of Veterinary and Animal Sciences, University of Copenhagen, Dyrlægevej 88, 1870 Frederiksberg C, DenmarkCenter for Vaccine Research, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen S, DenmarkPorcine reproductive and respiratory syndrome virus (PRRSV) causes severe respiratory distress and reproductive failure in swine. Modified live virus (MLV) vaccines provide the highest degree of protection and are most often the preferred choice. While somewhat protective, the use of MLVs is accompanied by multiple safety issues, why safer alternatives are urgently needed. Here, we describe the generation of virus replicon particles (VRPs) based on a classical swine fever virus genome incapable of producing infectious progeny and designed to express conserved PRRSV-2 cytotoxic T-cell epitopes. Eighteen pigs matched with the epitopes by their swine leucocyte antigen-profiles were vaccinated (N = 11, test group) or sham-vaccinated (N = 7, control group) with the VRPs and subsequently challenged with PRRSV-2. The responses to vaccination and challenge were monitored using serological, immunological, and virological analyses. Challenge virus load in serum did not differ significantly between the groups, whereas the virus load in the caudal part of the lung was significantly lower in the test group compared to the control group. The number of peptide-induced interferon-γ secreting cells after challenge was higher and more frequent in the test group than in the control group. Together, our results provide indications of a shapeable PRRSV-specific cell-mediated immune response that may inspire future development of effective PRRSV vaccines.https://www.mdpi.com/2076-393X/9/3/208porcine reproductive and respiratory syndrome virus (PRRSV)virus replicon particles (VRP)classical swine fever virus (CSFV)viral vectorvaccinepolyepitope antigen
spellingShingle Simon Welner
Nicolas Ruggli
Matthias Liniger
Artur Summerfield
Lars Erik Larsen
Gregers Jungersen
Reduced Virus Load in Lungs of Pigs Challenged with Porcine Reproductive and Respiratory Syndrome Virus after Vaccination with Virus Replicon Particles Encoding Conserved PRRSV Cytotoxic T-Cell Epitopes
Vaccines
porcine reproductive and respiratory syndrome virus (PRRSV)
virus replicon particles (VRP)
classical swine fever virus (CSFV)
viral vector
vaccine
polyepitope antigen
title Reduced Virus Load in Lungs of Pigs Challenged with Porcine Reproductive and Respiratory Syndrome Virus after Vaccination with Virus Replicon Particles Encoding Conserved PRRSV Cytotoxic T-Cell Epitopes
title_full Reduced Virus Load in Lungs of Pigs Challenged with Porcine Reproductive and Respiratory Syndrome Virus after Vaccination with Virus Replicon Particles Encoding Conserved PRRSV Cytotoxic T-Cell Epitopes
title_fullStr Reduced Virus Load in Lungs of Pigs Challenged with Porcine Reproductive and Respiratory Syndrome Virus after Vaccination with Virus Replicon Particles Encoding Conserved PRRSV Cytotoxic T-Cell Epitopes
title_full_unstemmed Reduced Virus Load in Lungs of Pigs Challenged with Porcine Reproductive and Respiratory Syndrome Virus after Vaccination with Virus Replicon Particles Encoding Conserved PRRSV Cytotoxic T-Cell Epitopes
title_short Reduced Virus Load in Lungs of Pigs Challenged with Porcine Reproductive and Respiratory Syndrome Virus after Vaccination with Virus Replicon Particles Encoding Conserved PRRSV Cytotoxic T-Cell Epitopes
title_sort reduced virus load in lungs of pigs challenged with porcine reproductive and respiratory syndrome virus after vaccination with virus replicon particles encoding conserved prrsv cytotoxic t cell epitopes
topic porcine reproductive and respiratory syndrome virus (PRRSV)
virus replicon particles (VRP)
classical swine fever virus (CSFV)
viral vector
vaccine
polyepitope antigen
url https://www.mdpi.com/2076-393X/9/3/208
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