VACCINATION WITH STREPTOCOCCAL EXTRACELLULAR CYSTEINE PROTEASE (INTERLEUKIN-1-BETA CONVERTASE) PROTECTS MICE AGAINST CHALLENGE WITH HETEROLOGOUS GROUP-A STREPTOCOCCI

Virtually all clinical isolates of group A streptococci secrete a high ly conserved extracellular cysteine protease that cleaves human fibron ectin and vitronectin, and converts IL-1 beta precursor to biologicall y active IL-1 beta. Based on the high degree of gene conservation with in the species and its role in host pathogenicity, it was postulated t hat antibodies to the cysteine protease would confer protective immuni ty against S. pyogenes infection. To test this hypothesis, Swiss CD1 m ice were intraperitoneally administered either saline, rabbit IgG, or IgG from rabbits immunized with the protease, and challenged with a hi ghly virulent(minimum lethal dose similar to 10 cfu) clinical isolate of S. pyogenes expressing a heterologous cysteine protease. The result s indicate that mice administered IgG from rabbits immunized with puri fied cysteine protease had significantly enhanced survival when compar ed with mice given either non-specific rabbit IgG (log rank test; X(2) ; p=0.0195) or saline (log rank test; X(2); p=0.0002). Moreover, mice actively immunized with the cysteine protease had a significantly long er time to death than the control group (log rank test; X(2); p=0.0418 ). The results show that the cysteine protease elicits non-type-specif ic immunity to challenge with heterologous S. pyogenes.