Abstract
Group A Streptococcus (GAS) causes a variety of diseases globally. The DNases in GAS promote GAS evasion of neutrophil killing by degrading neutrophil extracellular traps (NETs). Sda1 is a prophage-encoded DNase associated with virulent GAS strains. However, protective immunity against Sda1 has not been determined. In this study, we explored the potential of Sda1 as a vaccine candidate. Sda1 was used as a vaccine to immunize mice intranasally. The effect of anti-Sda1 IgG in neutralizing degradation of NETs was determined and the protective role of Sda1 was investigated with intranasal and systemic challenge models. Antigen-specific antibodies were induced in the sera and pharyngeal mucosal site after Sda1 immunization. The anti-Sda1 IgG efficiently prevented degradation of NETs by supernatant samples from different GAS serotypes with or without Sda1. Sda1 immunization promoted clearance of GAS from the nasopharynx independent of GAS serotypes but did not reduce lethality after systemic GAS challenge. Anti-Sda1 antibody can neutralize degradation of NETs by Sda1 and other phage-encoded DNases and decrease GAS colonization at the nasopharynx across serotypes. These results indicate that Sda1 can be a potential vaccine candidate for reduction in GAS reservoir and GAS tonsillitis-associated diseases.
Highlights
Group A Streptococcus (GAS) species cause more than 700 million human infections each year [1], resulting in over half a million deaths globally [2]
To estimate the potential utility of the Mu-Sda1 as a vaccine candidate, mice were immunized with Mu-Sda1 i.n. and samples of serum and mouthwash from the mice were taken to determine the immunogenicity of Mu-Sda1
Anti-Sda1 antibody was not detected in mice that were infected with GAS (Figure 2A–C)
Summary
Group A Streptococcus (GAS) species cause more than 700 million human infections each year [1], resulting in over half a million deaths globally [2]. In response to inflammatory stimuli, neutrophils migrate from the circulating blood to infected tissues, where they efficiently eradicate pathogens through phagocytosis, release of reactive oxygen species, and degranulation [5]. Aside from these well-documented mechanisms, neutrophils are able to extrude neutrophil extracellular traps (NETs), which consist of DNA lattices composed of antimicrobial molecules, to entrap and facilitate the killing of microbial pathogens [6]. The DNases of GAS have been identified as virulence factors and contribute significantly to disease progression by protecting GAS against neutrophil killing through degrading of NETs [8]. At least one of the DNases is produced by all strains of GAS and multiple DNases can be produced by a single GAS strain [8]
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