title: Novel conserved group A streptococcal proteins identified by the antigenome technology as vaccine candidates for a non-M protein-based vaccine.
abstract: Group A streptococci (GAS) can cause a wide variety of human infections ranging from asymptomatic colonization to life-threatening invasive diseases. Although antibiotic treatment is very effective, when left untreated, Streptococcus pyogenes infections can lead to poststreptococcal sequelae and severe disease causing significant morbidity and mortality worldwide. To aid the development of a non-M protein-based prophylactic vaccine for the prevention of group A streptococcal infections, we identified novel immunogenic proteins using genomic surface display libraries and human serum antibodies from donors exposed to or infected by S. pyogenes. Vaccine candidate antigens were further selected based on animal protection in murine lethal-sepsis models with intranasal or intravenous challenge with two different M serotype strains. The nine protective antigens identified are highly conserved; eight of them show more than 97% sequence identity in 13 published genomes as well as in approximately 50 clinical isolates tested. Since the functions of the selected vaccine candidates are largely unknown, we generated deletion mutants for three of the protective antigens and observed that deletion of the gene encoding Spy1536 drastically reduced binding of GAS cells to host extracellular matrix proteins, due to reduced surface expression of GAS proteins such as Spy0269 and M protein. The protective, highly conserved antigens identified in this study are promising candidates for the development of an M-type-independent, protein-based vaccine to prevent infection by S. pyogenes.
authors.affiliation: Intercell AG, Campus Vienna Biocenter 3, 1030 Vienna, Austria.
authors.forename: Andrea
authors.initials: A
authors.lastname: Fritzer
authors.forename: Beatrice M
authors.initials: BM
authors.lastname: Senn
authors.forename: Duc Bui
authors.initials: DB
authors.lastname: Minh
authors.forename: Markus
authors.initials: M
authors.lastname: Hanner
authors.forename: Dieter
authors.initials: D
authors.lastname: Gelbmann
authors.forename: Birgit
authors.initials: B
authors.lastname: Noiges
authors.forename: Tamás
authors.initials: T
authors.lastname: Henics
authors.forename: Kai
authors.initials: K
authors.lastname: Schulze
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Guzman
authors.forename: John
authors.initials: J
authors.lastname: Goodacre
authors.forename: Alexander
authors.initials: A
authors.lastname: von Gabain
authors.forename: Eszter
authors.initials: E
authors.lastname: Nagy
authors.forename: Andreas L
authors.initials: AL
authors.lastname: Meinke
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000032:analysis / Q000235:genetics / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins / Q000032:analysis; D001426:Bacterial Proteins / Q000276:immunology*; D002352:Carrier Proteins / Q000032:analysis; D004195:Disease Models, Animal; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D016680:Genome, Bacterial; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D022541:Streptococcal Vaccines / Q000276:immunology*; D013297:Streptococcus pyogenes / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D002352:Carrier Proteins; D016326:Extracellular Matrix Proteins; D022541:Streptococcal Vaccines; C014689:streptococcal M protein