Group A streptococcus is an important human pathogen that causes a variety of infections ranging in severity from pharyngitis and pyoderma to severe invasive diseases such as necrotizing fasciitis and toxic shock syndrome. Streptococcal non-suppurative sequelae like acute rheumatic fever and rheumatic heart disease remain major public health problems among most of the world’s population. The use of antibiotics and an improved standard of living have not significantly eliminated the high morbidity and mortality of group A streptococcal infections as seen by many outbreaks of rheumatic fever and invasive disease in the United States and Europe. Observations of increased incidence of macrolide resistance among isolates of group a streptococci, as well as reports of clinical and microbiological failures after penicillin treatment make the development of a safe and efficacious vaccine more urgent than ever. Among the different surface proteins that have been considered as potential candidate vaccines, the group A streptococcal C5a peptidase (SCPA) plays a major role as a virulence factor by allowing the group A streptococci to establish a mucosal site of infection. The objective of the present study was to explore the human immunogenicity of SCPA after natural infection with group A streptococcus using a standardized enzyme linked immunosorbent assay (ELISA).