title: Conserved anchorless surface proteins as group A streptococcal vaccine candidates.
abstract: Streptococcus pyogenes (group A Streptococcus (GAS)) causes ∼700 million human infections each year, resulting in over 500,000 deaths. The development of a commercial GAS vaccine is hampered by the occurrence of many unique GAS serotypes, antigenic variation within the same serotype, differences in serotype geographical distribution, and the production of antibodies cross-reactive with human tissue that may lead to autoimmune disease. Several independent studies have documented a number of GAS cell wall-associated or secreted metabolic enzymes that contain neither N-terminal leader sequences nor C-terminal cell wall anchors. Here, we applied a proteomic analysis of serotype M1T1 GAS cell wall extracts for the purpose of vaccine development. This approach catalogued several anchorless proteins and identified two protective vaccine candidates, arginine deiminase and trigger factor. These surface-exposed enzymes are expressed across multiple GAS serotypes exhibiting ≥99% amino acid sequence identity. Vaccine safety concerns are alleviated by the observation that these vaccine candidates lack human homologs, while sera from human populations suffering repeated GAS infections and high levels of autoimmune complications do not recognize these enzymes. Our study demonstrates anchorless cell surface antigens as promising vaccine candidates for the prevention of GAS disease.
authors.affiliation: School of Biological Sciences, University of Wollongong, Wollongong, NSW, 2522, Australia.
authors.forename: Anna
authors.initials: A
authors.lastname: Henningham
authors.forename: Emiliano
authors.initials: E
authors.lastname: Chiarot
authors.forename: Christine M
authors.initials: CM
authors.lastname: Gillen
authors.forename: Jason N
authors.initials: JN
authors.lastname: Cole
authors.forename: Manfred
authors.initials: M
authors.lastname: Rohde
authors.forename: Marcus
authors.initials: M
authors.lastname: Fulde
authors.forename: Vidiya
authors.initials: V
authors.lastname: Ramachandran
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Cork
authors.forename: Jon
authors.initials: J
authors.lastname: Hartas
authors.forename: Graham
authors.initials: G
authors.lastname: Magor
authors.forename: Steven P
authors.initials: SP
authors.lastname: Djordjevic
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Cordwell
authors.forename: Bostjan
authors.initials: B
authors.lastname: Kobe
authors.forename: Kabada S
authors.initials: KS
authors.lastname: Sriprakash
authors.forename: Victor
authors.initials: V
authors.lastname: Nizet
authors.forename: G S
authors.initials: GS
authors.lastname: Chhatwal
authors.forename: Immaculada Y R
authors.initials: IY
authors.lastname: Margarit
authors.forename: Michael R
authors.initials: MR
authors.lastname: Batzloff
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Walker
mesh_terms: D000293:Adolescent; D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology / Q000378:metabolism*; D002473:Cell Wall / Q000276:immunology / Q000378:metabolism*; D002648:Child; D005260:Female; D006801:Humans; D006867:Hydrolases / Q000276:immunology / Q000378:metabolism*; D007106:Immune Sera / Q000276:immunology; D007110:Immunity, Active; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016253:Microscopy, Immunoelectron; D019696:Peptidylprolyl Isomerase / Q000276:immunology / Q000378:metabolism*; D020543:Proteome / Q000276:immunology / Q000378:metabolism; D011817:Rabbits; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism; D013290:Streptococcal Infections / Q000276:immunology / Q000517:prevention & control*; D022541:Streptococcal Vaccines / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism*; D013297:Streptococcus pyogenes / Q000201:enzymology / Q000276:immunology* / Q000648:ultrastructure; D014611:Vaccination; D055815:Young Adult
chemical_list: D001426:Bacterial Proteins; D007106:Immune Sera; D020543:Proteome; D011994:Recombinant Proteins; D022541:Streptococcal Vaccines; D006867:Hydrolases; C019723:arginine deiminase; D019696:Peptidylprolyl Isomerase