A Self-Assembling β-Annulus Nanoparticle Vaccine Incorporating OX40L Confers Partial Protection Against NADC30-Like PRRSV in Piglets

Abstract

Porcine reproductive and respiratory syndrome (PRRS) remains one of the most economically significant viral diseases affecting the global swine industry, and currently available commercial vaccines provide only limited protection against circulating PRRS virus (PRRSV) strains. Therefore, alternative vaccination strategies are urgently needed to enhance protection against PRRSV infection. In this study, selected antigenic regions derived from the PRRSV structural proteins GP3, GP4, GP5, and M were incorporated into a β-annulus peptide-based nanoparticle scaffold derived from tomato bushy stunt virus (TBSV), and the resulting construct was further fused with the immunostimulatory molecule OX40L. The resulting OX40L-β-MEs protein formed nanoscale particles and was evaluated for immunogenicity and protective efficacy in piglets. Immunization with the OX40L-β-MEs nanoparticle vaccine induced measurable PRRSV-specific humoral responses and cellular immune-related responses in piglets. Following the challenge with the NADC30-like PRRSV strain GX-3264, piglets in the OX40L-β-MEs group showed shorter fever duration, reduced serum viremia and lung viral loads, and milder pulmonary lesions compared with PBS controls. In summary, these findings demonstrate that the β-annulus-based nanoparticle formulation can induce measurable immune responses and provide partial protection against NADC30-like PRRSV challenge, supporting further evaluation of this strategy for PRRSV vaccine development.