{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T23:22:07Z","timestamp":1792624927585,"version":"4.5.0"},"reference-count":61,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2016,2,2]],"date-time":"2016-02-02T00:00:00Z","timestamp":1454371200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/3.0\/"},{"start":{"date-parts":[[2016,3,2]],"date-time":"2016-03-02T00:00:00Z","timestamp":1456876800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01 AI088754"],"award-info":[{"award-number":["R01 AI088754"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2016,3,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Treatment of\n            <jats:named-content content-type=\"genus-species\">Staphylococcus aureus<\/jats:named-content>\n            infections has become increasingly difficult because of the emergence of multidrug-resistant isolates. Development of a vaccine to prevent staphylococcal infections remains a priority. To determine whether clumping factor A (ClfA) is a good target protein for inclusion in a multivalent vaccine, we evaluated its efficacy in a variety of relevant staphylococcal infection models, challenging with different\n            <jats:named-content content-type=\"genus-species\">S. aureus<\/jats:named-content>\n            strains. ClfA adsorbed to Alhydrogel and mixed with Sigma Adjuvant System was more immunogenic and stimulated a more robust Th17 response than ClfA administered with alum alone. ClfA immunization induced the production of functional antibodies in rabbits and mice that blocked\n            <jats:named-content content-type=\"genus-species\">S. aureus<\/jats:named-content>\n            binding to fibrinogen and were opsonic for\n            <jats:named-content content-type=\"genus-species\">S. aureus<\/jats:named-content>\n            strains that produced little or no capsular polysaccharide. Mice immunized with ClfA showed a modest reduction in the bacterial burden recovered from subcutaneous abscesses provoked by\n            <jats:named-content content-type=\"genus-species\">S. aureus<\/jats:named-content>\n            USA300 strain LAC. In addition, the ClfA vaccine reduced lethality in a sepsis model following challenge with strain Newman, but not ST80. Vaccination with ClfA did not protect against surgical wound infection, renal abscess formation, or bacteremia. Passive immunization with antibodies to ClfA did not protect against staphylococcal bacteremia in mice or catheter-induced endocarditis in rats. Some enhancement of bacteremia was observed by ClfA immunization or passive administration of ClfA antibodies when mice were challenged by the intraperitoneal route. Although rodent models of staphylococcal infection have their limitations, our data do not support the inclusion of ClfA in an\n            <jats:named-content content-type=\"genus-species\">S. aureus<\/jats:named-content>\n            multivalent vaccine.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Antibiotics are often ineffective in eradicating\n            <jats:named-content content-type=\"genus-species\">Staphylococcus aureus<\/jats:named-content>\n            infections, and thus, a preventative vaccine is sorely needed. Two single-component vaccines and two immunoglobulin preparations failed to meet their designated endpoints in phase III clinical trials. Importantly, recipients of an\n            <jats:named-content content-type=\"genus-species\">S. aureus<\/jats:named-content>\n            surface protein (iron surface determinant B) vaccine who developed a staphylococcal infection experienced a higher rate of multiorgan failure and mortality than placebo controls, raising safety concerns. Multicomponent\n            <jats:named-content content-type=\"genus-species\">S. aureus<\/jats:named-content>\n            vaccines have now been generated, and several include surface protein clumping factor A (ClfA). We immunized mice with ClfA and generated a robust T cell response and serum antibodies that were functional\n            <jats:italic>in vitro<\/jats:italic>\n            . Nonetheless, ClfA was not protective in a number of relevant animal models of\n            <jats:named-content content-type=\"genus-species\">S. aureus<\/jats:named-content>\n            infection, and high levels of ClfA antibodies enhanced bacteremia when mice were challenged with community-acquired methicillin-resistant\n            <jats:named-content content-type=\"genus-species\">S. aureus<\/jats:named-content>\n            strains. Evidence supporting ClfA as a vaccine component is lacking.\n          <\/jats:p>","DOI":"10.1128\/mbio.02232-15","type":"journal-article","created":{"date-parts":[[2016,2,3]],"date-time":"2016-02-03T02:03:28Z","timestamp":1454465008000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":26,"title":["Preclinical Efficacy of Clumping Factor A in Prevention of Staphylococcus aureus Infection"],"prefix":"10.1128","volume":"7","author":[{"given":"Xue","family":"Li","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, Massachusetts, USA"},{"name":"Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaogang","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher D.","family":"Thompson","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saeyoung","family":"Park","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan Beom","family":"Park","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, Massachusetts, USA"},{"name":"Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean C.","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199808203390806"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2013.10423"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI18535"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2200"},{"key":"e_1_3_2_6_2","unstructured":"Smeltzer MS Lee CY Harik N Hart ME Crossley K Jefferson K Archer G Fowler V. 2009. 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