{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T07:59:24Z","timestamp":1787731164108,"version":"build-2784847793"},"reference-count":56,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2018,11,1]],"date-time":"2018-11-01T00:00:00Z","timestamp":1541030400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Novel therapeutics against multidrug-resistant Neisseria gonorrhoeae are urgently needed. Gonococcal lipooligosaccharide often expresses lacto-N-neotetraose (LNnT), which becomes sialylated in vivo, enhancing factor H (FH) binding and contributing to the organism\u2019s ability to resist killing by complement. We previously showed that FH domains 18\u201320 (with a D-to-G mutation at position 1119 in domain 19) fused to Fc (FHD1119G\/Fc) displayed complement-dependent bactericidal activity in vitro and attenuated gonococcal vaginal colonization of mice. Gonococcal lipooligosaccharide phase variation can result in loss of LNnT expression. Loss of sialylated LNnT, although associated with a considerable fitness cost, could decrease efficacy of FHD1119G\/Fc. Similar to N. meningitidis, gonococci also bind FH domains 6 and 7 through Neisserial surface protein A (NspA). In this study, we show that a fusion protein comprising FH domains 6 and 7 fused to human IgG1 Fc (FH6,7\/Fc) bound to 15 wild-type antimicrobial resistant isolates of N. gonorrhoeae and to each of six lgtA gonococcal deletion mutants. FH6,7\/Fc mediated complement-dependent killing of 8 of the 15 wild-type gonococcal isolates and effectively reduced the duration and burden of vaginal colonization of three gonococcal strains tested in wild-type mice, including two strains that resisted complement-dependent killing but on which FH6,7\/Fc enhanced C3 deposition. FH\/Fc lost efficacy when Fc was mutated to abrogate C1q binding and in C1q\u2212\/\u2212 mice, highlighting the requirement of the classical pathway for its activity. Targeting gonococci with FH6,7\/Fc provides an additional immunotherapeutic approach against multidrug-resistant gonorrhea.<\/jats:p>","DOI":"10.4049\/jimmunol.1701666","type":"journal-article","created":{"date-parts":[[2018,9,28]],"date-time":"2018-09-28T14:16:28Z","timestamp":1538144188000},"page":"2700-2709","source":"Crossref","is-referenced-by-count":23,"title":["Human Factor H Domains 6 and 7 Fused to IgG1 Fc Are Immunotherapeutic against <i>Neisseria gonorrhoeae<\/i>"],"prefix":"10.1093","volume":"201","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0832-9954","authenticated-orcid":false,"given":"Jutamas","family":"Shaughnessy","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School , Worcester, MA 01605"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9469-9083","authenticated-orcid":false,"given":"Lisa A","family":"Lewis","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School , Worcester, MA 01605"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2237-2898","authenticated-orcid":false,"given":"Bo","family":"Zheng","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School , Worcester, MA 01605"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6912-6937","authenticated-orcid":false,"given":"Caleb","family":"Carr","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School , Worcester, MA 01605"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isaac","family":"Bass","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School , Worcester, MA 01605"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunita","family":"Gulati","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School , Worcester, MA 01605"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosane B","family":"DeOliveira","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School , Worcester, MA 01605"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Severin","family":"Gose","sequence":"additional","affiliation":[{"name":"San Francisco Department of Public Health , San Francisco, CA 94102"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George W","family":"Reed","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School , Worcester, MA 01605"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Botto","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Imperial College London , London SW7 2AZ ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter A","family":"Rice","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School , Worcester, MA 01605"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjay","family":"Ram","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School , Worcester, MA 01605"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,11,1]]},"reference":[{"key":"2025030417573957700_r1","doi-asserted-by":"crossref","first-page":"e0143304","DOI":"10.1371\/journal.pone.0143304","article-title":"Global estimates of the prevalence and incidence of four curable sexually transmitted infections in 2012 based on systematic review and global reporting","volume":"10","author":"Newman","year":"2015","journal-title":"PLoS One"},{"key":"2025030417573957700_r2","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1128\/CMR.00010-14","article-title":"Antimicrobial resistance in Neisseria gonorrhoeae in the 21st century: past, evolution, and future","volume":"27","author":"Unemo","year":"2014","journal-title":"Clin. Microbiol. Rev."},{"key":"2025030417573957700_r3","doi-asserted-by":"crossref","first-page":"1858","DOI":"10.1093\/jac\/dks162","article-title":"Molecular characterization of two high-level ceftriaxone-resistant Neisseria gonorrhoeae isolates detected in Catalonia, Spain","volume":"67","author":"C\u00e1mara","year":"2012","journal-title":"J. Antimicrob. Chemother."},{"key":"2025030417573957700_r4","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1186\/1471-2334-13-570","article-title":"Neisseria gonorrhoeae and extended-spectrum cephalosporins in California: surveillance and molecular detection of mosaic penA","volume":"13","author":"Gose","year":"2013","journal-title":"BMC Infect. 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