Development and delivery of a peptide-based vaccine against group A Streptococcus

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Group A Streptococcus
Streptococcus pyogenes (group A Streptococcus (GAS)) is a beta-hemolytic Gram-positive bacterium. It causes a variety of human diseases ranging from common bacterial pharyngitis (‘strep throat’) to life-threatening disease such as streptococcal toxic shock syndrome. Importantly, it is also responsible for post-infectious autoimmune complications including rheumatic fever and rheumatic heart disease. These diseases are the major cause of GAS-related morbidity and mortality – it was recently estimated that around 70 million individuals worldwide have rheumatic heart disease, which was expected to result in 1.4 million deaths per annum [1].

While antibiotics are generally effective against GAS, repeated reinfection and late intervention are major contributors to the development of autoimmunity, resulting in mortality, especially in developing countries and indigenous populations. This highlights the need to develop an effective vaccine against GAS [2]. Remarkably, despite 100 years of effort, no vaccine candidates against this infection have reached the market.

Vaccines

The first attempts to produce a vaccine against GAS utilized the classical approach – heat-killed GAS bacteria [3]. However, this bacterium caused autoimmune responses and these trials were abandoned. The M-protein, an outer membrane protein and GAS virulence factor, was then selected for vaccine development. However, early clinical trials again suggested the risk of autoimmune responses caused by immunization with the whole protein. Although other proteins could also be utilized as antigens for vaccine development, M-protein stimulated the most robust protective immunity [4].

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