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Although antibiotic treatment is very effective, when left untreated,<jats:italic>Streptococcus pyogenes<\/jats:italic>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<jats:italic>S. pyogenes<\/jats:italic>. 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<jats:italic>S. pyogenes<\/jats:italic>.<\/jats:p>","DOI":"10.1128\/iai.00295-10","type":"journal-article","created":{"date-parts":[[2010,7,13]],"date-time":"2010-07-13T03:10:39Z","timestamp":1278990639000},"page":"4051-4067","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":65,"title":["Novel Conserved Group A Streptococcal Proteins Identified by the Antigenome Technology as Vaccine Candidates for a Non-M Protein-Based Vaccine"],"prefix":"10.1128","volume":"78","author":[{"given":"Andrea","family":"Fritzer","sequence":"first","affiliation":[{"name":"Intercell AG, Campus Vienna Biocenter 3, 1030 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrice M.","family":"Senn","sequence":"additional","affiliation":[{"name":"Intercell AG, Campus Vienna Biocenter 3, 1030 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duc Bui","family":"Minh","sequence":"additional","affiliation":[{"name":"Intercell AG, Campus Vienna Biocenter 3, 1030 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Hanner","sequence":"additional","affiliation":[{"name":"Intercell AG, Campus Vienna Biocenter 3, 1030 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dieter","family":"Gelbmann","sequence":"additional","affiliation":[{"name":"Intercell AG, Campus Vienna Biocenter 3, 1030 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgit","family":"Noiges","sequence":"additional","affiliation":[{"name":"Intercell AG, Campus Vienna Biocenter 3, 1030 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tama\u0301s","family":"Henics","sequence":"additional","affiliation":[{"name":"Intercell AG, Campus Vienna Biocenter 3, 1030 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Schulze","sequence":"additional","affiliation":[{"name":"Helmholtz Center for Infection Research, Department of Vaccinology and Applied Microbiology, Inhoffenstrasse 7, 38124 Braunschweig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos A.","family":"Guzman","sequence":"additional","affiliation":[{"name":"Helmholtz Center for Infection Research, Department of Vaccinology and Applied Microbiology, Inhoffenstrasse 7, 38124 Braunschweig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Goodacre","sequence":"additional","affiliation":[{"name":"School of Health &amp; Medicine at Lancaster University, Lancaster LA1 4YD, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"von Gabain","sequence":"additional","affiliation":[{"name":"Intercell AG, Campus Vienna Biocenter 3, 1030 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eszter","family":"Nagy","sequence":"additional","affiliation":[{"name":"Intercell AG, Campus Vienna Biocenter 3, 1030 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas L.","family":"Meinke","sequence":"additional","affiliation":[{"name":"Intercell AG, Campus Vienna Biocenter 3, 1030 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.41.6.2385-2390.2003"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/292457a0"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)74408-1"},{"key":"e_1_3_3_5_2","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.4049\/jimmunol.145.4.1251","volume":"145","year":"1990","unstructured":"Bessen, D., and V. 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