{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T07:17:58Z","timestamp":1778656678796,"version":"3.51.4"},"reference-count":36,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2014,10,1]],"date-time":"2014-10-01T00:00:00Z","timestamp":1412121600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Clin Vaccine Immunol"],"published-print":{"date-parts":[[2014,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The emergence of antimicrobial resistance among several medically important pathogens represents a serious threat to human health globally and necessitates the development of novel therapeutics. Complement forms a key arm of innate immune defenses against invading pathogens. A mechanism of complement evasion employed by many pathogens is binding of complement inhibitors, including factor H (FH), a key downregulator of the alternative pathway. Most FH-binding bacteria engage FH through regions in FH spanned by domains 6 and 7 and\/or 18 through 20. We created a chimeric protein that comprised human FH domains 6 and 7 fused to human IgG1 Fc (FH6,7\/HuFc) and tested its activity as an immunotherapeutic against\n            <jats:named-content content-type=\"genus-species\">Neisseria meningitidis<\/jats:named-content>\n            , which binds FH through domains 6 and 7. FH6,7\/HuFc bound to meningococci and effectively blocked FH binding to bacteria. FH6,7\/HuFc enhanced human C3 and C4 deposition and facilitated complement-mediated killing in a dose-responsive manner; complement activation and killing were classical pathway dependent. To investigate\n            <jats:italic>in vivo<\/jats:italic>\n            efficacy, infant Wistar rats were treated intraperitoneally (IP) with different doses of FH6,7\/HuFc and challenged 2 h later with serogroup C strain 4243 given IP. At 8 to 9 h after the challenge, the FH6,7\/HuFc-treated rats had &gt;100-fold fewer CFU per ml of blood than control animals pretreated with phosphate-buffered saline (PBS) or FH18\u201320\/HuFc, which does not bind to meningococci (\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.0001). These data provide proof of concept of the utility of FH\/Fc fusion proteins as anti-infective immunotherapeutics. Because many microbes share a common binding region(s) in FH, FH\/Fc chimeric proteins may be a promising candidate for adjunctive therapy against drug-resistant pathogens.\n          <\/jats:p>","DOI":"10.1128\/cvi.00444-14","type":"journal-article","created":{"date-parts":[[2014,8,21]],"date-time":"2014-08-21T06:52:23Z","timestamp":1408603943000},"page":"1452-1459","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":27,"title":["Fusion Protein Comprising Factor H Domains 6 and 7 and Human IgG1 Fc as an Antibacterial Immunotherapeutic"],"prefix":"10.1128","volume":"21","author":[{"given":"Jutamas","family":"Shaughnessy","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David M.","family":"Vu","sequence":"additional","affiliation":[{"name":"Children's Hospital Oakland Research Institute, Oakland, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rahi","family":"Punjabi","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Judit","family":"Serra-Pladevall","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosane B.","family":"DeOliveira","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan M.","family":"Granoff","sequence":"additional","affiliation":[{"name":"Children's Hospital Oakland Research Institute, Oakland, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanjay","family":"Ram","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","volume-title":"Antibiotic resistance threats in the United States, 2013","year":"2013","unstructured":". 2013. 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