In the present study, we further indicated that SPE B binds to human serum C3 through its C-terminal domain, and the major C3-binding motif is located between residues 376 and 398 in SPE B. Furthermore, immunization with a 23mer synthetic peptide that consisted of residues 376–398 of SPE B protected mice from a lethal GAS invasive infection. The gene discussed is C3; the disease is flatulence.