Abstract
Group A streptococcus (GAS) is known to cause a broad spectrum of illness, from pharyngitis and impetigo, to autoimmune sequelae such as rheumatic heart disease, and invasive diseases. It is a significant cause of infectious disease morbidity and mortality worldwide, but no efficacious vaccine is currently available. Progress in GAS vaccine development has been hindered by a number of obstacles, including a lack of standardization in immunoassays and the need to define human correlates of protection. In this review, we have examined the current immunoassays used in both GAS and other organisms, and explored the various challenges in their implementation in order to propose potential future directions to identify a correlate of protection and facilitate the development of M protein-based vaccines, which are currently the main GAS vaccine candidates.
Highlights
Group A streptococcus (GAS, otherwise known as Streptococcus pyogenes) is one of the most important causes of infectious disease morbidity and mortality, with an estimated prevalence of severe disease of at least 18.1 million cases leading to more than 500,000 deaths annually [1]
In the case of other bacterial pathogens, such as Streptococcus pneumoniae and group B streptococcus (GBS), for which vaccines are widely available or development is underway, correlate of protection (CoP) provide a means of assessing the true efficacy and immunogenicity of potential vaccines [6, 7]
Non-M protein virulence factors such as C5a peptidase, lipoteichoic acid, protein F, and Streptococcal fibronectin-binding protein have been shown in animal studies to raise protective antibodies that contribute to host immunity, in preventing colonization [18, 25]
Summary
Group A streptococcus (GAS, otherwise known as Streptococcus pyogenes) is one of the most important causes of infectious disease morbidity and mortality, with an estimated prevalence of severe disease of at least 18.1 million cases leading to more than 500,000 deaths annually [1]. Much of the burden exists in less developed countries where control strategies are difficult to implement and ensure efficacy. A vaccine is widely acknowledged as an important strategy to reduce the burden of GAS disease globally. A key element in vaccine development is the availability of a validated and standardized immunoassay that correlates with immune protection. Despite decades of research, there is no single standardized immunoassay and certainly no human correlate of protection (CoP) established for GAS [5]. In the case of other bacterial pathogens, such as Streptococcus pneumoniae and group B streptococcus (GBS), for which vaccines are widely available or development is underway, CoPs provide a means of assessing the true efficacy and immunogenicity of potential vaccines [6, 7]
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