Abstract
Streptococcus pyogenes, also known as Group A Streptococcus (GAS), is a Gram-positive human-exclusive pathogen, responsible for more than 500 000 deaths annually worldwide. Upon infection, GAS commonly triggers mild symptoms such as pharyngitis, pyoderma and fever. However, recurrent infections or prolonged exposure to GAS might lead to life-threatening conditions. Necrotizing fasciitis, streptococcal toxic shock syndrome and post-immune mediated diseases, such as poststreptococcal glomerulonephritis, acute rheumatic fever and rheumatic heart disease, contribute to very high mortality rates in non-industrialized countries. Though an initial reduction in GAS infections was observed in high-income countries, global outbreaks of GAS, causing rheumatic fever and acute poststreptococcal glomerulonephritis, have been reported over the last decade. At the same time, our understanding of GAS pathogenesis and transmission has vastly increased, with detailed insight into the various stages of infection, beginning with adhesion, colonization and evasion of the host immune system. Despite deeper knowledge of the impact of GAS on the human body, the development of a successful vaccine for prophylaxis of GAS remains outstanding. In this review, we discuss the challenges involved in identifying a universal GAS vaccine and describe several potential vaccine candidates that we believe warrant pursuit.
Highlights
Group A Streptococcus (GAS) or Streptococcus pyogenes is a virulent Gram-positive pathogen responsible for a plethora of diseases ranging from mild, superficial infections to lifethreatening diseases with high morbidity and mortality in humans [1]
The vaccine candidates in pre-clinical trials include non-M antigens such as streptococcal pyrogenic exotoxin, streptococcal C5a peptidase, streptolysin O, group A carbohydrate and derivatives, streptococcal pyrogenic exotoxin B, fibronectin-binding protein S. pyogenes fibronectin-binding adhesin (SfbI), Streptococcus pyogenes cell envelope proteinase, arginine deiminase and serum opacity factor
By van Sorge et al, using mouse and rabbit GAS infection models revealed that Group A Carbohydrate (GAC) antibodies raised against the polyrhamnose backbone promoted opsonophagocytic killing of multiple GAS serotypes, suggesting the GAC backbone could be viewed as a potential universal vaccine for GAS infection [29]
Summary
Group A Streptococcus (GAS) or Streptococcus pyogenes is a virulent Gram-positive pathogen responsible for a plethora of diseases ranging from mild, superficial infections to lifethreatening diseases with high morbidity and mortality in humans [1]. A recent study demonstrated that a rare mutation, found in the penicillin-binding protein 2B in two GAS strains, confers reduced susceptibility to β-lactam antibiotics from the penicillin family, including amoxicillin [8]. The only non-protein GAS vaccine candidate antigen is a carbohydrate component of the ubiquitous surface-exposed Group A Carbohydrate (GAC) [29]. There are drawbacks to the use of non-M protein GAS antigens such as the high level of sequence variation and low sequence coverage across global GAS strains. These protein vaccine targets must be present in all strains to achieve protection against all GAS isolates. This review focuses on (i) outlining pathogenic mechanisms of GAS, (ii) the challenges of developing a universal GAS vaccine, and (iii) the vaccine candidates currently being developed to prevent GAS infections
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