We identified mechanisms that can explain an aspect of the potent immunogenicity of the Bartha vaccine against the porcine alphaherpesvirus pseudorabies virus. We showed that and revealed how the Bartha vaccine triggers strongly increased cytokine responses by plasmacytoid dendritic cells (pDC).

Our findings may help to rationally design vaccines against other (alphaherpes)virus vaccines.

Interestingly, we show that the increased pDC response correlates with a faster production of extracellular infectious virus in Bartha-infected epithelial cells and a reduced production of non-infectious light (L-)particles which are known to suppress pDC responses. We show that the large deletion in the unique short (US) region of the viral genome in Bartha is responsible for these effects, and in particular the viral gE/gI and US2 genes that are deleted in Bartha.

The attenuated Bartha vaccine strain was generated by repeated passage in cell culture. Our data therefore suggest that this cell passage culture has led to a micro-evolution of PRV towards increased production of extracellular virus (which is beneficial for virus spread in cell culture) and reduced expression of L-particles. This appears to have resulted in a reduced ability of the virus to suppress the host immune response, including pDC.

https://journals.asm.org/doi/10.1128/jvi.02199-21