Group A streptococcal (GrAS) infections continue to pose a significant threat to human health. It is estimated that annually in the United States there are approximately 15 million cases of streptococcal pharyngitis, with a total cost of $2 billion. Streptococcal pharyngitis may trigger acute rheumatic fever resulting in chronic valvular disease with its attendant morbidity and mortality. In addition, the Centers for Disease Control and Prevention estimates that in the United States there are approximately 10,000 to 15,000 cases of serious, invasive GrAS infections annually, many of which result in death. A safe and effective vaccine that prevents GrAS infections could have a significant impact on human health.