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Characterization of a novel leucine-rich repeat protein antigen from group B streptococci that elicits protective
Ravin Seepersaud1, Sean B Hanniffy, Peter Mayne
1Cortecs Centre for Vaccine Discovery, Department of Pathology, University of Cambridge, Cambridge, UK.
Insights
Group B Streptococcus (GBS) can cause severe neonatal infections. A novel surface antigen, LrrG, was identified and shown to protect mice against GBS, suggesting its potential as a vaccine target.
Area of Science:
- Microbiology
- Immunology
- Vaccine Development
Background:
- Group B Streptococcus (GBS) is a leading cause of invasive neonatal disease.
- Maternal GBS colonization is a significant risk factor for infant infection.
- Surface antigens are potential targets for vaccines to prevent GBS infection.
Purpose of the Study:
- To identify novel GBS surface antigens for vaccine development.
- To investigate the role of the identified LrrG protein in GBS pathogenesis.
- To evaluate the immunogenicity and protective efficacy of LrrG.
Main Methods:
- Genetic screening to identify exported GBS proteins.
- Southern blotting to assess lrrG gene distribution.
- In vitro adhesion assays using recombinant LrrG protein.
- Immunization of mice with recombinant LrrG and subsequent challenge with GBS.
Main Results:
- A novel LPXTG-anchored surface antigen, LrrG, containing leucine-rich repeat (LRR) motifs was identified.
- The lrrG gene is conserved across all tested GBS serotypes and has a homologue in Streptococcus pyogenes.
- Recombinant LrrG demonstrated adherence to epithelial cells in vitro.
- Immunization with LrrG induced a strong IgG response and protected mice against lethal GBS challenge.
Conclusions:
- LrrG is a conserved GBS surface protein with potential adhesive properties.
- LrrG is a promising candidate antigen for a GBS vaccine to prevent neonatal invasive disease.
Abstract:
Group B streptococci (GBS) usually behave as commensal organisms that asymptomatically colonize the gastrointestinal and urogenital tracts of adults. However, GBS are also pathogens and the leading bacterial cause of life-threatening invasive disease in neonates. While the events leading to transmission and disease in neonates remain unclear, GBS carriage and level of colonization in the mother have been shown to be significant risk factors associated with invasive infection. Surface antigens represent ideal vaccine targets for eliciting antibodies that can act as opsonins and/or inhibit colonization and invasion. Using a genetic screen for exported proteins in GBS, we identified a gene, designated lrrG, that encodes a novel LPXTG anchored surface antigen containing leucine-rich repeat (LRR) motifs found in bacterial invasins and other members of the LRR protein family. Southern blotting showed that lrrG was present in all GBS strains tested, representing the nine serotypes, and revealed the presence of an lrrG homologue in Streptococcus pyogenes. Recombinant LrrG protein was shown in vitro to adhere to epithelial cells in a dose-dependent manner, suggesting that it may function as an adhesion factor in GBS. More importantly, immunization with recombinant LrrG elicited a strong immunoglobulin G response in CBA/ca mice and protected against lethal challenge with virulent GBS. The data presented in this report suggest that this conserved protein is a highly promising candidate antigen for use in a GBS vaccine.
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