TY - JOUR

T1 - 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

AU - Welner, Simon

AU - Ruggli, Nicolas

AU - Liniger, Matthias

AU - Summerfield, Artur

AU - Larsen, Lars Erik

AU - Jungersen, Gregers

PY - 2021

Y1 - 2021

N2 - 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 antigenprofiles 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.

AB - 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 antigenprofiles 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.

KW - Cell-mediated immunity

KW - Classical swine fever virus (CSFV)

KW - Cytotoxic T cells

KW - Polyepitope antigen

KW - Porcine reproductive and respiratory syndrome virus (PRRSV)

KW - Vaccine

KW - Viral vector

KW - Virus replicon particles (VRP)

U2 - 10.3390/vaccines9030208

DO - 10.3390/vaccines9030208

M3 - Journal article

C2 - 33801369

AN - SCOPUS:85102697568

VL - 9

SP - 1

EP - 22

JO - Vaccines

JF - Vaccines

SN - 2076-393X

IS - 3

M1 - 208

ER -