Recent Advances in the Development of Peptide Vaccines and Their Delivery Systems against Group A Streptococcus

Abstract

Group A Streptococcus (GAS) infection can cause a variety of diseases in humans, ranging from common sore throats and skin infections, to more invasive diseases and life-threatening post-infectious diseases, such as rheumatic fever and rheumatic heart disease. Although research has been ongoing since 1923, vaccines against GAS are still not available to the public. Traditional approaches taken to develop vaccines for GAS failed due to poor efficacy and safety. Fortunately, headway has been made and modern subunit vaccines that administer minimal bacterial components provide an opportunity to finally overcome previous hurdles in GAS vaccine development. This review details the major antigens and strategies used for GAS vaccine development. The combination of antigen selection, peptide epitope modification and delivery systems have resulted in the discovery of promising peptide vaccines against GAS; these are currently in preclinical and clinical studies.

Polyacrylate–Peptide Antigen Conjugate as a Single-Dose Oral Vaccine against Group A Streptococcus

“…The risk of a resurgence of invasive diseases and poor disease management in developing countries also dictates the need for better solutions to control GAS infection. Unfortunately, no commercial vaccine is available for GAS infection [19,20].…”

“…However, advances in epitope mapping have enabled the identification of several B-cell epitopes based on M protein [24]. New-generation GAS vaccine designs are focusing on the conserved C-repeat region epitopes, as they have shown potential for providing protection against most GAS strains without inducing autoimmune responses [20,[25][26][27]. The α-helical B-cell epitope J8 (QAEDKVKQSREAKKQVEKALKQLEDKVQ) derived from M protein has recently passed Phase I clinical trials [28,29].…”

Opsonic Activity of Conservative Versus Variable Regions of the Group A Streptococcus M Protein

“…Tripalmitoyl- S -glyceryl cysteine (Pam 3 Cys) and dipalmitoyl-S-glyceryl cysteine (Pam 2 Cys), identified from Braun’s lipoprotein from Escherichia coli , was developed as a fully-synthetic vaccine adjuvant and applied in the development of vaccines, including the HIV vaccine (in clinical trials) and the GAS vaccine (preclinical trials). Pam 3 Cys has also been approved by the Food and Drug Administration of the United States for the Neisseria meningitides vaccine [ 6 , 38 ]. The lipid core peptide is a fully synthetic lipo-peptide-based vaccine delivery system based on lipoamino acids with a long alkyl side chain (e.g., 12 to 20 carbons in length) coupled to a peptide epitope.…”

“…Peptides as antigens are a modern vaccine approach that uses minimal microbial components to stimulate adaptive immunity against a pathogen [ 6 ]. Peptides are seen as a safer alternative to using the whole organism or protein, which in the case of GAS, have been associated with allergic and autoimmune responses [ 6 ].…”

“…Peptides as antigens are a modern vaccine approach that uses minimal microbial components to stimulate adaptive immunity against a pathogen [ 6 ]. Peptides are seen as a safer alternative to using the whole organism or protein, which in the case of GAS, have been associated with allergic and autoimmune responses [ 6 ]. The GAS M protein ( Figure 1 ), a coiled-coil homodimer surface-anchored protein encoded by the emm gene, has been identified as one of the major virulence factors of GAS infection preventing opsonophagocytosis, and as a result, has been a major focus in GAS vaccine development [ 7 ].…”