TbpB-based oral mucosal vaccine provides heterologous protection against Glässer’s disease caused by different serovars of Spanish field isolates ofGlaesserella parasuis

Background Glaesserella parasuis has a substantial impact on the pig production as the primary agent of Glässer’s disease, particularly affecting nursery and early fattening stages. Current prophylactic measures, mainly based in serovar-specific bacterins administered parenterally to sows, face limitations due to maternal immunity, which may interfere with the active immunization of piglets. The mucosal administration of TbpB-based subunit vaccines offers a promising approach to overcome these limitations for the control of the disease in weaning piglets. This study evaluates the immunogenicity and heterologous protection of the oral mucosal TbpB Y167A subunit vaccine in colostrum-deprived piglets challenged with four G. parasuis clinical isolates belonging to different TbpB clusters and serovars (SVs) recovered from Spanish pig farms. Results The mucosal administration of a two-dose TbpB-based vaccine induced a robust humoral immune response in immunized colostrum-deprived piglets, significantly increasing IgA ( p < 0.01) and IgM ( p < 0.01) concentration 15 days after the second dose. Subsequent infection challenge with four G. parasuis clinical isolates demonstrated heterologous protection, markedly improving survival rates (OR: 8.45; CI 95%: 4.97-14.36) and significantly reducing clinical signs and lesions, regardless of the G. parasuis TbpB cluster and serovar. The vaccine not only reduced G. parasuis colonization in the respiratory tract of immunized piglets ( p < 0.0001), but also in systemic target tissues, such as the tarsus and carpus joints, liver, and brain ( p < 0.05). Further immunohistochemical analysis in different lung locations revealed a significantly lower macrophage count in immunized piglets ( p < 0.0001). Conclusions Overall, this study demonstrates that the oral mucosal administration of the TbpB Y167A subunits vaccine in piglets provides effective heterologous protection against different virulent European G. parasuis field isolates, significantly reducing bacterial colonization and dissemination. These facts position this TbpB-based vaccine as a leading candidate for a universal vaccine against Glässer’s disease.