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Invasive disease caused by drug-resistant strains, designated MRSA (methicillin-resistant S. aureus), is associated with failure of antibiotic therapy and elevated mortality. Here we review polysaccharide-conjugate and subunit vaccines that were designed to prevent S. aureus infection in patients at risk of bacteremia or surgical wound infection but failed to reach their clinical endpoints. We also discuss vaccines with ongoing trials for combinations of polysaccharide-conjugates and subunits. S. aureus colonization and invasive disease are not associated with the development of protective immune responses, which is attributable to a large spectrum of immune evasion factors. Two evasive strategies, assembly of protective fibrin shields via coagulases and protein A\u2013mediated B cell superantigen activity, are discussed as possible vaccine targets. Although correlates for protective immunity are not yet known, opsonophagocytic killing of staphylococci by phagocytic cells offers opportunities to establish such criteria.<\/jats:p>","DOI":"10.1084\/jem.20160569","type":"journal-article","created":{"date-parts":[[2016,8,15]],"date-time":"2016-08-15T10:07:30Z","timestamp":1471255650000},"page":"1645-1653","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":75,"title":["<i>Staphylococcus aureus<\/i>\n                    vaccines: Deviating from the carol"],"prefix":"10.1084","volume":"213","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6482-9633","authenticated-orcid":false,"given":"Dominique","family":"Missiakas","sequence":"first","affiliation":[{"name":"Department of Microbiology, University of Chicago, Chicago, IL 60637"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9652-3823","authenticated-orcid":false,"given":"Olaf","family":"Schneewind","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Chicago, Chicago, IL 60637"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2016,8,15]]},"reference":[{"key":"2023072603263587500_bib1","doi-asserted-by":"publisher","first-page":"1585","DOI":"10.4161\/hv.21872","article-title":"Development of a multicomponent Staphylococcus aureus vaccine designed to counter multiple bacterial virulence factors","volume":"8","author":"Anderson","year":"2012","journal-title":"Hum. 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