A Modular T4 Phage-Based Nanoparticle Displaying Multiepitopes Provides Cross-Serotype Protection against...

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.