Correlates of Protection for M Protein-Based Vaccines against Group A Streptococcus

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.

Figure 1

Schematic representation of incidence of group A streptococcal diseases by age using data from epidemiological reports [, –33].

Figure 2

Process of immunity and correlates of protection. Immune markers 1 and 2 (IM-1, IM-2) are correlates of protection, but only IM-1 is a surrogate. Arrows imply direct causal relationships. Figure adapted from WHO [34].