Cross-serotype protection against group A Streptococcal infections induced by immunization with SPy_2191

Pooja Sanduja, Manish Gupta, Vikas Kumar Somani, Vikas Yadav, Meenakshi Dua, Emanuel Hanski, Abhinay Sharma, Rakesh Bhatnagar and Atul Kumar Johri ()
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Pooja Sanduja: Jawaharlal Nehru University
Manish Gupta: Jawaharlal Nehru University
Vikas Kumar Somani: Jawaharlal Nehru University
Vikas Yadav: Jawaharlal Nehru University
Meenakshi Dua: Jawaharlal Nehru University
Emanuel Hanski: The Hebrew University of Jerusalem
Abhinay Sharma: The Hebrew University of Jerusalem
Rakesh Bhatnagar: Banaras Hindu University
Atul Kumar Johri: Jawaharlal Nehru University

Nature Communications, 2020, vol. 11, issue 1, 1-11

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-17299-x

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