Modified live vaccine strains of porcine reproductive and respiratory syndrome virus cause immune system dysregulation similar to wild strains

• DOI: 10.3389/fimmu.2023.1292381
• Publication Date: 2024-01-12T04:31:22Z
• Authors: Katerina Stepanova; Miroslav Toman; Jana Sinkorova; Simon Sinkora; Sarka Pfeiferova; Helena Kupcova Sk...; Salim Abuhajiar; Romana Moutelikova; Jiri Salat; Hana Stepanova; Katerina Nechvata...; Lenka Leva; Petra Hermanova; Mirka Kratochvilova; Blanka Dusankova; Marek Sinkora; Vratislav Horak; Tomas Hudcovic; John E. Butler; Marek Sinkora
• Keywords: Immune Dysregulation; Attenuated vaccine

Porcine reproductive and respiratory syndrome virus (PRRSV) emerged about 30 years ago continues to cause major economic losses in the pork industry. The lack of effective modified live vaccines (MLV) allows pandemic continue. We have previously shown that wild strains PRRSV affect nascent T cell repertoire thymus, deplete clones recognizing viral epitopes essential for neutralization, while triggering a chronic, robust, but ineffective antibody response. Therefore, we hypothesized current MLV are inappropriate because they similar damage fail prevent viral-induced dysregulation adaptive immunity. tested three demonstrate all comparable negative effect on thymocytes vitro. Further vivo studies compared development cells peripheral lymphocytes, production young piglets. These were used mixture determine whether at least some them behave similarly type 1 or 2. Both same immune dysregulations. include depletion T-cell precursors, alteration TCR repertoire, necrobiosis corticomedullary junctions, low body weight gain, decreased thymic cellularity, virus-neutralizing antibodies, non-neutralizing anti-PRRSV antibodies different isotypes. results may explain why use animals be their potentially dangerous. alternative vaccines, such as subunit mRNA improved MLV, needed control pandemic.