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

Simon Welner; Nicolas Ruggli; Matthias Liniger; Artur Summerfield; Lars Erik Larsen; Gregers Jungersen

doi:10.3390/vaccines9030208

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 (Basel). 2021 Mar 2;9(3):208. doi: 10.3390/vaccines9030208.

Authors

Simon Welner¹, Nicolas Ruggli^{2

3}, Matthias Liniger^{2

3}, Artur Summerfield^{2

3}, Lars Erik Larsen¹, Gregers Jungersen⁴

Affiliations

¹ Section for Veterinary Clinical Microbiology, Department of Veterinary and Animal Sciences, University of Copenhagen, Dyrlægevej 88, 1870 Frederiksberg C, Denmark.
² Institute of Virology and Immunology IVI, Sensemattstrasse 293, 3147 Mittelhäusern, Switzerland.
³ Department of Infectious Diseases and Pathobiology (DIP), Vetsuisse Faculty, University of Bern, Länggassstrasse 120, 3012 Bern, Switzerland.
⁴ Center for Vaccine Research, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen S, Denmark.

Abstract

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.

Keywords: cell-mediated immunity; classical swine fever virus (CSFV); cytotoxic T cells; polyepitope antigen; porcine reproductive and respiratory syndrome virus (PRRSV); vaccine; viral vector; virus replicon particles (VRP).