Progress in M-protein-based subunit vaccines to prevent rheumatic fever and rheumatic heart disease

Infection with the human bacterial pathogen group A Streptococcus (GAS) is estimated to cause over 500,000 deaths per year, the majority of which are related to rheumatic fever (RF) and rheumatic heart disease (RHD). While GAS is an important cause of morbidity and mortality globally, the burden of GAS-associated diseases is greater in less developed countries and in indigenous populations of developed countries. The antiphagocytic bacterial surface M protein is a major candidate antigen in the development of a vaccine to prevent GAS infection and RF/RHD. A major obstacle, however, in the development of an M-protein-based vaccine is the widespread diversity of circulating GAS strains and M protein types. Added to this is the possibility of inducing autoimmunity following vaccination as a result of molecular mimicry between the M protein and host tissue proteins. Research has been aimed at the development of a safe GAS vaccine that is able to induce broad-coverage protective immunity. The development of subunit vaccine approaches targeting the M protein using various vaccine delivery technologies is the focus of this review.