title: Characterization of a novel leucine-rich repeat protein antigen from group B streptococci that elicits protective immunity.
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.
authors.affiliation: Cortecs Centre for Vaccine Discovery, Department of Pathology, University of Cambridge, Cambridge, UK.
authors.forename: Ravin
authors.initials: R
authors.lastname: Seepersaud
authors.forename: Sean B
authors.initials: SB
authors.lastname: Hanniffy
authors.forename: Peter
authors.initials: P
authors.lastname: Mayne
authors.forename: Phil
authors.initials: P
authors.lastname: Sizer
authors.forename: Richard
authors.initials: R
authors.lastname: Le Page
authors.forename: Jerry M
authors.initials: JM
authors.lastname: Wells
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood*; D000942:Antigens, Bacterial / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D003001:Cloning, Molecular; D006801:Humans; D007114:Immunization; D000090263:Leucine-Rich Repeat Proteins; D051379:Mice; D008808:Mice, Inbred CBA; D008969:Molecular Sequence Data; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020449:Repetitive Sequences, Amino Acid; D017422:Sequence Analysis, DNA; D013290:Streptococcal Infections / Q000382:microbiology / Q000517:prevention & control*; D022541:Streptococcal Vaccines / Q000008:administration & dosage / Q000276:immunology; D013292:Streptococcus agalactiae / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D000090263:Leucine-Rich Repeat Proteins; C498397:LrrG protein, Streptococus agalactiae; D011506:Proteins; D022541:Streptococcal Vaccines
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