Vaccination of autologous dendritic cells induces early protection against the Foot-and-mouth disease virus in pigs by enhancing T-cell immunity

Abstract

Abstract Foot-and-mouth disease virus (FMDV) remains a challenge for cloven-hooved animals. The currently-licensed FMDV vaccines induce neutralizing antibody (NAb)-mediated protection but have early protection defects. Dendritic cell (DC) vaccines have shown great potency in producing rapid T-cell immunity in humans and mice. However, this strategy has not been elaborately explored in domestic animals, and it is unknown how much effectiveness can be achieved for a specific pathogen in pigs. In this study, we tested the potency of DC immunization in the protective immunity against FMDV in pigs. Autologous DCs were differentiated from each pig's periphery blood mononuclear cells, pulsed with inactivated FMDV (iFMDV-DC), and injected into the original pigs. The cellular immune responses and protective efficacy elicited by the iFMDV-DC were examined by multicolor flow cytometry and tested by FMDV challenge. The results showed that autologous iFMDV-DC immunization induces predominantly FMDV-specific IFN-γ-producing CD4+ T cells and cytotoxic CD8+ T cells (CTLs), high NAb titers, compared to the inactivated FMDV vaccine, and accelerated the development of memory CD4 and CD8 T cells, which was concomitantly associated with early protection against FMDV virulent strain in pigs. Early protection was associated with the rapid proliferation of secondary T cell response after the FMDV challenge and conferred more by secondary CD8 effector memory T cells rather than NAbs. These results demonstrated that rapid induction of cellular immunity by DC immunization is critical to improving early protection. To enhance cytotoxic CD8+ T cells in addition to Th1 immunity via a strategy or adjuvant comparable to DC immunization may facilitate the development of more effective FMDV vaccines and overcoming the defects of the current FMDV vaccines in the future.