Provided are streptolysin S (SLS) polypeptides, peptides, and variants thereof, antibodies directed thereto, and isolated nucleic acids encoding such proteins. In one embodiment, a method is provided wherein a synthetic peptide of SLS is used to elicit an immune response specific for SLS in a subject to treat or prevent a streptococcal infection. In other embodiments, antibodies that neutralize the hemolytic activity of the SLS toxin may be used as a vaccinating agent.