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

K. Stepanova, M. Toman, J. Sinkorova, S. Sinkora, S. Pfeiferova, H. Kupcova Skalnikova, S. Abuhajiar, R. Moutelikova, J. Salat, H. Stepanova, K. Nechvatalova, L. Leva, P. Hermanova, M. Kratochvilova, B. Dusankova, M. Sinkora, V. Horak, T....

. 2023 ; 14 (-) : 1292381. [pub] 20240112

Jazyk angličtina Země Švýcarsko

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc24007584

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

Citace poskytuje Crossref.org

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$a INTRODUCTION: Porcine reproductive and respiratory syndrome virus (PRRSV) emerged about 30 years ago and continues to cause major economic losses in the pork industry. The lack of effective modified live vaccines (MLV) allows the pandemic to continue. BACKGROUND AND OBJECTIVE: We have previously shown that wild strains of PRRSV affect the nascent T cell repertoire in the thymus, deplete T cell clones recognizing viral epitopes essential for neutralization, while triggering a chronic, robust, but ineffective antibody response. Therefore, we hypothesized that the current MLV are inappropriate because they cause similar damage and fail to prevent viral-induced dysregulation of adaptive immunity. METHODS: We tested three MLV strains to demonstrate that all have a comparable negative effect on thymocytes in vitro. Further in vivo studies compared the development of T cells in the thymus, peripheral lymphocytes, and antibody production in young piglets. These three MLV strains were used in a mixture to determine whether at least some of them behave similarly to the wild virus type 1 or type 2. RESULTS: Both the wild and MLV strains cause the same immune dysregulations. These include depletion of T-cell precursors, alteration of the TCR repertoire, necrobiosis at corticomedullary junctions, low body weight gain, decreased thymic cellularity, lack of virus-neutralizing antibodies, and production of non-neutralizing anti-PRRSV antibodies of different isotypes. DISCUSSION AND CONCLUSION: The results may explain why the use of current MLV in young animals may be ineffective and why their use may be potentially dangerous. Therefore, alternative vaccines, such as subunit or mRNA vaccines or improved MLV, are needed to control the PRRSV pandemic.
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$a Toman, Miroslav $u Department of Infectious Diseases and Preventive Medicine, Veterinary Research Institute, Brno, Czechia
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$a Kupcova Skalnikova, Helena $u Laboratory of Applied Proteome Analyses and Research Center PIGMOD (Pig Models of Diseases), Institute of Animal Physiology and Genetics, Czech Academy of Sciences, Libechov, Czechia $u Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University, Prague, Czechia
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$a Abuhajiar, Salim $u Laboratory of Applied Proteome Analyses and Research Center PIGMOD (Pig Models of Diseases), Institute of Animal Physiology and Genetics, Czech Academy of Sciences, Libechov, Czechia $u Department of Cell Biology, Faculty of Science, Charles University, Prague, Czechia
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$a Moutelikova, Romana $u Department of Infectious Diseases and Preventive Medicine, Veterinary Research Institute, Brno, Czechia
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$a Salat, Jiri $u Department of Infectious Diseases and Preventive Medicine, Veterinary Research Institute, Brno, Czechia
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$a Leva, Lenka $u Department of Infectious Diseases and Preventive Medicine, Veterinary Research Institute, Brno, Czechia
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$a Hermanova, Petra $u Laboratory of Gnotobiology, Institute of Microbiology, Czech Academy of Sciences, Novy Hradek, Czechia
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$a Butler, John E $u Department of Microbiology and Immunology, Carver College of Medicine, University of Iowa, Iowa City, IA, United States
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