Abstract
No commercial vaccine exists against Group A streptococci (GAS; Streptococcus pyogenes) and only little is known about anti-GAS protective immunity. In our effort to discover new protective vaccine candidates, we selected 21 antigens based on an in silico evaluation. These were all well-conserved among different GAS strains, upregulated in host-pathogen interaction studies, and predicted to be extracellular or associated with the surface of the bacteria. The antigens were tested for both antibody recognition and T cell responses in human adults and children. The antigenicity of a selected group of antigens was further validated using a high-density peptide array technology that also identified the linear epitopes. Based on immunological recognition, four targets were selected and tested for protective capabilities in an experimental GAS infection model in mice. Shown for the first time, three of these targets (spy0469, spy1228 and spy1801) conferred significant protection whereas one (spy1643) did not.
Highlights
Group A streptococci (GAS; Streptococcus pyogenes) are major human pathogens causing a wide variety of diseases ranging from uncomplicated infections like pharyngitis and impetigo to life-threatening invasive diseases1
It is already well-established that antibodies have protective capacity12–17 but cellular responses have been suggested to possess antibody-independent protective capacity in a murine GAS infection model18–20
We show that the three antigens were able to protect against infection with GAS in a murine infection model
Summary
Group A streptococci (GAS; Streptococcus pyogenes) are major human pathogens causing a wide variety of diseases ranging from uncomplicated infections like pharyngitis and impetigo to life-threatening invasive diseases. The most studied antigen is the surface M protein where both the variable N-terminal and its conserved C-terminal region have been proposed as vaccine candidates. The goal for this study was to identify new protective non-M protein vaccine candidates. We decided that our vaccine candidates should be recognized by both antibodies and T cells. It is already well-established that antibodies have protective capacity but cellular responses have been suggested to possess antibody-independent protective capacity in a murine GAS infection model. In a recent study we showed that the majority of both children and adults possess antibody responses, and strong Th1 responses against GAS antigens. MtsA; metal ABC transporter substrate binding Lipoprot FtsK; DNA translocase Putative 42 kDa protein, surface antigen Chromosome segregation ATPase Putative membrane spanning protein Putative membrane associated protein Putative lipoprotein, nucleoside-binding protein
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