Cross-serotype protection against group A Streptococcal infections induced by immunization with SPy_2191
Open Access
- 15 July 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Communications
- Vol. 11 (1), 1-11
- https://doi.org/10.1038/s41467-020-17299-x
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.Keywords
Funding Information
- University Grants Commission
- Israel Science Foundation
This publication has 54 references indexed in Scilit:
- Multi High-Throughput Approach for Highly Selective Identification of Vaccine Candidates: the Group A Streptococcus CaseMolecular & Cellular Proteomics, 2012
- Interferon-γ-producing immature myeloid cells confer protection against severe invasive group A Streptococcus infectionsNature Communications, 2012
- New 30-valent M protein-based vaccine evokes cross-opsonic antibodies against non-vaccine serotypes of group A streptococciVaccine, 2011
- Streptococcus pyogenes M49 Plasminogen/Plasmin Binding Facilitates Keratinocyte Invasion via Integrin-Integrin-linked Kinase (ILK) Pathways and Protects from Macrophage KillingPublished by Elsevier BV ,2011
- Type I Interferon Production Induced by Streptococcus pyogenes-Derived Nucleic Acids Is Required for Host ProtectionPLoS Pathogens, 2011
- Novel Conserved Group A Streptococcal Proteins Identified by the Antigenome Technology as Vaccine Candidates for a Non-M Protein-Based VaccineInfection and Immunity, 2010
- Bacterial surface proteins and vaccinesF1000 Biology Reports, 2010
- Large scale multiplex PCR improves pathogen detection by DNA microarraysBMC Microbiology, 2009
- Association of the shuffling of Streptococcus pyogenes clones and the fluctuation of scarlet fever cases between 2000 and 2006 in central TaiwanBMC Microbiology, 2009
- Transcriptional and Proteomic Profiles of Group B Streptococcus Type V Reveal Potential Adherence Proteins Associated with High-Level InvasionInfection and Immunity, 2007