Chapter 14 - Group A Streptococcus Vaccines

Abstract

Substantial morbidity and mortality due to group A Streptococcus (GAS) diseases persist worldwide, yet development of safe and effective vaccines has been impeded by scientific, regulatory, and commercial obstacles. Most deaths from GAS occur in low- and middle-income countries, most due to rheumatic heart disease (RHD). New cases of RHD are now rarely seen in high-income countries outside of high-risk subgroups. In settings endemic for RHD, even the most intensive control efforts have only demonstrated a partial effect. In addition to RHD, severe life-threatening invasive GAS infections occur worldwide, often presenting so acutely that there is no realistic window for prevention with early antibiotic treatment. More common milder syndromes including pharyngitis and skin infections cause significant social and economic disruption and costs. Technically, development of GAS vaccines has been impeded by concerns that vaccine-induced responses might trigger autoimmunity and precipitate acute rheumatic fever (ARF), mimicking the relationship between GAS infection and the immunopathogenesis of ARF and RHD. The extensive strain diversity of GAS is a separate and additional technical challenge. Several approaches have attempted to address these safety and efficacy concerns, avoiding the inclusion of antigens suspected to be responsible for autoimmunity and adopting either a multivalent design or focusing on broadly conserved antigens. A reenergized global vaccine development effort has organized around the vision of a safe, globally effective, and affordable GAS vaccine to prevent acute GAS infections and associated antibiotic use, immune-mediated sequelae, and mortality. Its near-term aspiration is to demonstrate the safety and efficacy of a candidate vaccine against GAS pharyngitis and skin infections in children. Although RHD and severe invasive infections are the most fatal GAS syndromes, they are too uncommon and/or have too-long a latency period to be primary endpoints in clinical trials before licensure. Finally, demonstrating the value of a GAS vaccine to all stakeholders is crucial to attract the interest and investment from funders and industry required for development to proceed efficiently. This chapter will summarize the status of GAS vaccine research and development and the road ahead.