The efficacy of c-di-AMP as an immunopotentiator for inactivated PRV vaccine

Abstract Pseudorabies is an acute infectious disease caused by pseudorabies virus which bring huge losses to the swine industry. Compared to live vaccine, the inactivated Pseudorabies virus (PRV)vaccine is generally safe, but it could not elicit strong immunity protection as live vaccine. Improve the efficacy of the inactivated vaccines with immunopotentiator is a research hotspot. Viability-associated pathogen-related molecular patterns(vita-PAMPs) are a type of PAMPs that only exist in active microorganisms. Once entering the body, vita-PAMPs could quickly and efficiently initiate the immune response, and then produce a high level and lasting immune efficacy similar to live vaccine immunity. C-di-AMP is a type of vita-PAMPs which recognized by antigen presenting cell (APC), they can mobilize a high degree of inflammation and activate the adaptive immune response. Hence, we evaluate the effect of c-di-AMP on the efficacy of the pseudorabies inactivated vaccine using a murine model. The immunological enhancement characteristics of c-di-AMP were evaluated for PRV inactivated vaccine in mice. In this study, we measured the level of early inflammatory factors and the recruitment of antigen presenting cells in draining lymph nodes, the activation of follicular helper T cells (Tfh) and the formation of germinal center (GC) by flow cytometry analysis. We also tested the level of serum antibody and the duration of it. The result showed that PRV inactivated vaccine adding c-di-AMP promote the secretion of TNF-α, IL-1β, and IFN-β, recruitment of DCs, Mo and MPh at 7days post-immunization(dpi), and enhance murine antibody levels of PRV by promoting Tfh activated, which directly controls the magnitude of the GC B cell response. These results indicate that c-di-AMP can enhance the immunogenicity of PRV inactivated vaccines, thus providing a novel strategy for improving its efficacy.