Construction, characterization and evaluation of the protective efficacy of the Streptococcus suis double mutant strain ΔSsPep/ΔSsPspC as a live vaccine candidate in mice.

Abstract Streptococcus suis serotype 2 ( S. suis 2) causes sepsis and meningitis in piglets and humans, and results in one of the most serious bacterial diseases affecting the production of commercial pigs around the world. Due to the failure of the current inactivated vaccine to protect against the disease, development of a new attenuated live vaccine against S. suis 2 by deleting essential virulence factors is urgently needed. We have previously reported the construction and characterization of an SsPep single gene deletion mutant strain Δ SsPep based on S. suis 2. Our previous results have shown that SsPep plays a critical role in the pathogenesis of S. suis 2. In this study, a precisely defined double-deletion mutant Δ SsPep /Δ SsPspC of S. suis 2 without antibiotic-resistance markers was constructed based on Δ SsPep , and the levels of virulence of the wild-type (WT) and Δ SsPep /Δ SsPspC were compared in a mouse experimental infection model. We demonstrated that the double mutant Δ SsPep /Δ SsPspC was less virulent than the WT, and could induce a noticeable antibody response. Analysis of IgG subclasses (IgG1 and IgG2a) indicated that both Th1 and Th2 responses were induced by Δ SsPep /Δ SsPspC , although the IgG2a (Th1) response predominated over the IgG1 (Th2) response. Moreover, Δ SsPep /Δ SsPspC could confer 90% protective efficacy against challenge with a lethal dose of fully virulent S. suis 2. Taken together, these data demonstrate that Δ SsPep /Δ SsPspC can be used as an effective live vaccine and provide a novel strategy against infection of S. suis 2.