Development and immunological evaluation of a Streptococcus suis serotype 2 capsular polysaccharide conjugate vaccine

Streptococcus suis serotype 2 (SS2) is a major zoonotic pathogen responsible for severe infections in both pigs and humans. Despite its clinical significance, no effective vaccine is currently available, and the influence of capsular polysaccharide (CPS2) structural features on host immunity remains unclear. Here, we identified a fast-growing SS2 strain from a panel of 40 clinical isolates and established a novel, reliable CPS2 purification method. This approach combines polyethylenimine-mediated nucleic acid precipitation with phenol-based protein denaturation, eliminating the need for column chromatography and enabling gram-scale CPS2 recovery per liter of culture while preserving structural integrity. To examine the role of sialic acid, we compared antibody responses induced by native and desialylated CPS2 conjugates in mice, which revealed no significant differences. Based on this finding, a native CPS2 conjugate vaccine was subsequently evaluated in pigs, where it induced robust IgG responses and conferred significant protection against virulent SS2 challenge. The effects of different adjuvants and dosages were also investigated. Collectively, these results establish an efficient CPS2 production platform, clarify the limited impact of sialic acid on conjugate-induced antibody responses, and highlight the potential of CPS2-based conjugates as promising vaccine candidates against SS2 infection.