The highest prevalence of RHD in 5- to 14-years-old children is observed in developing and newly industrial¬ized countries, amounting to 5.7 cases per 1,000 population in sub-Saharan Africa and 2.2 cases per 1,000 population in south-central Asia. Even in industrialized countries, the prevalence is as high as 0.3 cases per 1,000 population. The substantial impact of S. pyogenes on human health and the associated high economic losses have motivated a long, extensive, and continuous search for a vaccine; a search that, after more than half a century, has not yet led to a licensed product on the market that prevents S. pyogenes infections or their sequelae in humans.