Vaccination of weaning piglets with the recombinant IgM degrading enzyme of Streptococcus suis (S. suis), rIde _Ssuis, elicits protection against disease caused by serotype (cps) 2 infection. In Europe, S. suis cps9 is at least as important as cps2 in causing severe herd problems associated with meningitis, septicemia and arthritis. The objective of this study was to determine humoral and cellular immunogenicities of rIde _Ssuis suckling piglet vaccination and to investigate protection against a virulent cps9 strain. Vaccination in the 2nd and 4th week of life with rIde _Ssuis and an oil-in-water adjuvant induced seroconversion against Ide _Ssuis in 13 of 20 vaccinated piglets. In the 5th week, survival of the S. suis cps9 strain was significantly reduced in the blood of prime-booster vaccinated piglets. After a 2nd booster vaccination Ide _Ssuis -reactive T helper (Th) cells partially producing TNF-α, IL-17A or IFN-ɣ were detectable in rIde _Ssuis -vaccinated but not in placebo-treated piglets and frequencies of Ide _Ssuis -reactive Th cells correlated with α-Ide _Ssuis-IgG levels. An intravenous challenge, conducted with a cps9 strain of sequence type (ST) 94, led to 89% mortality in placebo-treated piglets due to septicemia and meningitis. In contrast, all rIde _Ssuis prime-booster-booster vaccinated littermates survived the challenge despite signs of disease such as fever and lameness. In conclusion, the described rIde _Ssuis vaccination induces humoral and detectable Ide _Ssuis -reactive Th cell responses and leads to protection against a highly virulent cps9 strain.

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