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

猪繁殖与呼吸综合征病毒减毒活疫苗株引起与野生株类似的免疫系统失调

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作者:Katerina Stepanova, Miroslav Toman, Jana Sinkorova, Simon Sinkora, Sarka Pfeiferova, Helena Kupcova Skalnikova, Salim Abuhajiar, Romana Moutelikova, Jiri Salat, Hana Stepanova, Katerina Nechvatalova, Lenka Leva, Petra Hermanova, Mirka Kratochvilova, Blanka Dusankova, Marek Sinkora Jr, Vratislav Hora

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.

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.

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.

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.

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