A Modular T4 Phage-Based Nanoparticle Displaying Multiepitopes Provides Cross-Serotype Protection against Streptococcus suis in Mice and Swine.

Streptococcus suis is an important zoonotic pathogen that is widely distributed in the global swine industry. Our previous studies demonstrated that the bacterial elongation factor IF-2 protein provides protection against S. suis infection in mice. On this basis, the T-cell and B-cell epitopes of IF-2 were predicted and concatenated to generate the IF2-1 and IF2-2 polypeptides. We successfully constructed IF2-1-T4 and IF2-2-T4 nanoparticles on the basis of the IF-2 protein via the T4 in vivo assembly platform. Both IF2-1-T4 and IF2-2-T4 nanoparticles exhibited superior immunoprotective efficacy compared with IF-2 in mouse models, regardless of the presence of adjuvants. Among them, IF2-2-T4 showed the strongest protection and demonstrated the potential to induce cross-protection against multiple S. suis serotypes, providing a promising strategy for the development of broad-spectrum S. suis vaccines. Furthermore, this study systematically evaluated the immunoprotective efficacy of a recombinant T4 phage-based vaccine in a swine model and compared the effects of intramuscular and needle-free immunization routes. Collectively, these results establish a foundation for the application of T4 nanoparticle-based vaccines in swine and offer new insights into the design of cross-protective vaccines against S. suis and other bacterial pathogens.