Subunit Vaccine Targeting Phosphate ABC Transporter ATP-Binding Protein, PstB, Provides Cross-Protection against Streptococcus suis Serotype 2, 7, and 9 in Mice

Simple Summary Streptococcus suis is an important bacterial pathogen, causing meningitis, arthritis, and endocarditis in pigs. Infections caused by S. suis lead to significant economic losses in the pig industry worldwide. The increasing prevalence of antimicrobial resistance (AMR), resulting in heightened global regulations on antibiotic use in livestock, has highlighted the critical need for alternative S. suis control strategies, such as vaccination. In the present study, we evaluated the protective effect of a subunit protein-based vaccine, targeting the phosphate ABC transporter ATP-binding protein (PstB) of S. suis serotype 2. PstB was shown to be highly conserved across various S. suis isolates. In mice, a candidate vaccine targeting the PstB protein induced the production of high levels of cytokines IFN-gamma and IL-4, both considered to be important for protection against S. suis. Furthermore, the PstB-based vaccine was shown to provide a high level of (87.5%) protection against S. suis serotypes 2 and 9, with lower protection (62.5%) against S. suis serotype 7. These data indicate that PstB is a promising target antigen for development as a universal subunit vaccine against different S. suis serotypes. Streptococcus suis is a significant pathogen in pigs and a newly emerging zoonotic agent in humans. The presence of multiple serotypes and strains with diversified sequence types in pig herds highlights the need for the identification of broadly cross-reactive universal vaccine antigen targets, capable of providing cross-protection against S. suis infection. Subunit vaccines based on the conserved proteins shared between different S. suis serotypes are potential candidates for such a universally protective vaccine. In the present study, phosphate ABC transporter ATP-binding protein PstB (PstB), an immunogenic protein of the S. suis bacterium, was expressed and purified, and then subjected to cross-protection evaluation in mice. The PstB protein showed nearly 100% amino acid similarity across a panel of 31 S. suis isolates representing different serotypes, which were collected from different countries. A recombinant PstB (rPstB) protein (S. suis serotype 2) was recognized by rabbit sera specific to this serotype, and induced high levels of IFN-gamma and IL-4 in mice immunized with the recombinant protein. These cytokines are considered important for protection against S. suis infection. Immunization of mice with rPstB resulted in an 87.5% protection against challenge with S. suis serotype 2 and 9 strains, suggesting a high level of cross-protection for S. suis serotypes 2 and 9. A lower protection rate (62.5%) was observed in mice challenged with the S. suis serotype 7 strain. These data demonstrate that PstB is a promising target antigen for development as a component of a universal subunit vaccine against multiple S. suis serotypes.