Nanoparticle Vaccine Triggers Interferon-Gamma Production and Confers Protective Immunity against Porcine Reproductive and Respiratory Syndrome Virus

The swine industry annually suffers significant economic losses caused by porcine reproductive and respiratory syndrome virus (PRRSV). Because the available commercial vaccines have limited protective efficacy against epidemic PRRSV, there is an urgent need for innovative solutions. Nanoparticle vaccines induce robust immune responses and have become a promising direction in vaccine development. In this study, we designed and produced a self-assembling nanoparticle vaccine derived from thermophilic archaeal ferritin to combat epidemic PRRSV. First, multiple T cell epitopes targeting viral structural proteins were identified by IFN-γ screening after PRRSV infection. Three different self-assembled nanoparticles with epitopes targeting viral GP3, GP4, and GP5 proteins were constructed and mixed to generate a FeCocktail vaccine. Experiments showed that the FeCocktail vaccine effectively activated CD4⁺ and CD8⁺ T cells and effector memory T cells in mice. Piglets immunized with the FeCocktail vaccine generated specific antibodies and exhibited increased levels of PRRSV-specific IFN-γ produced by functional CD4⁺ and CD8⁺ cells. The FeCocktail also provided protective efficacy against PRRSV challenge, including mitigation of clinical symptoms, reduction of viral loads in serum and lungs, and the alleviation of lung tissue damage. In conclusion, this study offers a promising candidate vaccine for combating epidemic PRRSV, and affirms the utility of nanoparticle protein as a platform for next-generation PRRSV vaccine development.