Project 1

Project summary

Porcine reproductive and respiratory syndrome (PRRS) remains a substantial economic and animal welfare burden for pig production in Europe. The widely used modified live virus vaccines only provide protection against related strains and bear the risk of reversion to more virulent forms. Research on PRRS pathogenesis, immunity and vaccine development has mainly focused on the respiratory form of the disease, even though the reproductive form causes close to 45% of the economic losses. This application brings together leading experts in the field of PRRS pathology and immunology, including its re-productive form. We propose to investigate in depth the interplay between the immune system and PRRS virus (PRRSV) during late gestation, focusing on local processes at the maternal-foetal interface.

We will investigate whether immune responses in the maternal endometrium and foetal placenta con-tribute to protective immunity or immunopathology. We will utilise the different stages of foetal demise occurring in the same litter during PRRSV infection, ranging from viable to fully autolysed, and apply high-dimensional flow cytometry and immunofluorescence histology in combination with single-cell and spatial transcriptomics. Understanding the factors driving protective immunity versus immuno-pathology are essential to the development of protective vaccines. Based on our recently published findings, we will also investigate whether CD8 effector T cells derived from the foetal compartment of the placenta are specific for PRRSV and of foetal origin. For this, we will develop major histocompatibility class I tetramers binding to PRRSV-specific CD8 T cells. If the hypothesis of foetal immunity can be confirmed, it will open new research avenues, such as the possibility of developing vaccines tailored to the foetal immune system. Such vaccines would circumvent the interference with maternal immunity, which frequently limits vaccine efficacy when administered post-partum.