Abstract
Group A Streptococcus (GAS) infection causes a range of diseases, but vaccine development is hampered by the high number of serotypes. Here, using reverse vaccinology the authors identify SPy_2191 as a cross-protective vaccine candidate. From 18 initially identified surface proteins, only SPy_2191 is conserved, surface-exposed and inhibits both GAS adhesion and invasion. SPy_2191 immunization in mice generates bactericidal antibodies resulting in opsonophagocytic killing of prevalent and invasive GAS serotypes of different geographical regions, including M1 and M49 (India), M3.1 (Israel), M1 (UK) and M1 (USA). Resident splenocytes show higher interferon-γ and tumor necrosis factor-α secretion upon antigen re-stimulation, suggesting activation of cell-mediated immunity. SPy_2191 immunization significantly reduces streptococcal load in the organs and confers ~76-92% protection upon challenge with invasive GAS serotypes. Further, it significantly suppresses GAS pharyngeal colonization in mice mucosal infection model. Our findings suggest that SPy_2191 can act as a universal vaccine candidate against GAS infections.
Highlights
Group A Streptococcus (GAS) infection causes a range of diseases, but vaccine development is hampered by the high number of serotypes
Streptococcus pyogenes or GAS is a human pathogenic bacterium. It causes a range of suppurative diseases, invasive diseases [necrotizing fasciitis, streptococcal toxic shock syndrome (STSS)] and poststreptococcal sequel [Acute rheumatic fever (ARF), rheumatic heart disease (RHD), glomerulonephritis]
GAS serotype M49 that caused outbreaks in including M1 and M49 (India) and USA was used for this study as this serotype was found to be most invasive[27,28]
Summary
Group A Streptococcus (GAS) infection causes a range of diseases, but vaccine development is hampered by the high number of serotypes. SPy_2191 immunization in mice generates bactericidal antibodies resulting in opsonophagocytic killing of prevalent and invasive GAS serotypes of different geographical regions, including M1 and M49 (India), M3.1 (Israel), M1 (UK) and M1 (USA). The available 45 recombinant sera previously generated against these 52 and the other reported genes[20,21] are screened for their role in adherence and invasion Among those that are found to be involved in adherence are subsequently checked for their exposure from the surface of GAS serotypes of Indian origin. SPy_2191 tests as a potential vaccine candidate in the mouse model against five prevalent and invasive GAS serotypes from India, Israel, UK and USA. This finding highlights SPy_2191 as a promising universal vaccine candidate, in providing significant protection against the globally prevalent and invasive GAS serotypes in different geographical areas
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