Toll-like receptor ligands enhance the protective effects of vaccination against porcine reproductive and respiratory syndrome virus in swine

Porcine reproductive and respiratory syndrome virus (PRRSV) is mainly responsible for the heavy economic losses in pig industry in the world. Current vaccination strategies provide only a limited protection. Previous studies have demonstrated the immunostimulatory adjuvant effects of Toll-like receptor (TLR) ligands, synthetic double-stranded RNA polyriboinosinic polyribocytidylic [poly(I:C)], lipoteichoic acid (LTA) and CL097 in humans and animals. To study the effects of these compounds on the induction of PRRSV-specific immune responses, mice were immunized subcutaneously with killed virus (KV) antigens incorporating pairs of TLR ligands. It was found that poly(I:C) and CL097 induced the higher IFN-γ levels and PRRSV-specific antibodies, comparing with that KV with or without LTA in mice. Piglets were vaccinated with the KV mixed with poly(I:C) or CL097 and the protective effects of the vaccination were evaluated. The results showed that PRRSV-specific antibodies and T lymphocyte proliferation levels in KV mixed with poly(I:C) or CL097 groups were higher than those in KV group. Following challenge with PRRSV, pigs inoculated with KV mixed with poly(I:C) or CL097 showed lighter clinical signs, lower viremia and less pathological lesion of lungs, as compared to those of KV and challenge control groups. It indicated that co-administration of poly(I:C) and CL097 with killed PRRSV vaccine conferred higher protection against PRRSV challenge. TLR3 and TLR7/8 ligands are promising adjuvant candidates for the development of novel vaccines against PRRSV.