{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T07:58:57Z","timestamp":1787731137903,"version":"build-2784847793"},"reference-count":64,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2016,2,1]],"date-time":"2016-02-01T00:00:00Z","timestamp":1454284800000},"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":[[2016,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Neisseria gonorrhoeae, the causative agent of the sexually transmitted infection gonorrhea, has developed resistance to almost every conventional antibiotic. There is an urgent need to develop novel therapies against gonorrhea. Many pathogens, including N. gonorrhoeae, bind the complement inhibitor factor H (FH) to evade complement-dependent killing. Sialylation of gonococcal lipooligosaccharide, as occurs in vivo, augments binding of human FH through its domains 18\u201320 (FH18\u201320). We explored the use of fusing FH18\u201320 with IgG Fc (FH18\u201320\/Fc) to create a novel anti-infective immunotherapeutic. FH18\u201320 also binds to select host glycosaminoglycans to limit unwanted complement activation on host cells. To identify mutation(s) in FH18\u201320 that eliminated complement activation on host cells, yet maintained binding to N. gonorrhoeae, we created four mutations in domains 19 or 20 described in atypical hemolytic uremic syndrome that prevented binding of mutated fH to human erythrocytes. One of the mutant proteins (D to G at position 1119 in domain 19; FHD1119G\/Fc) facilitated complement-dependent killing of gonococci similar to unmodified FH18\u201320\/Fc but, unlike FH18\u201320\/Fc, did not lyse human erythrocytes. FHD1119G\/Fc bound to all (100%) of 15 sialylated clinical N. gonorrhoeae isolates tested (including three contemporary ceftriaxone-resistant strains), mediated complement-dependent killing of 10 of 15 (67%) strains, and enhanced C3 deposition (\u226510-fold above baseline levels) on each of the five isolates not directly killed by complement. FHD1119G\/Fc facilitated opsonophagocytic killing of a serum-resistant strain by human polymorphonuclear neutrophils. FHD1119G\/Fc administered intravaginally significantly reduced the duration and burden of gonococcal infection in the mouse vaginal colonization model. FHD1119G\/Fc represents a novel immunotherapeutic against multidrug-resistant N. gonorrhoeae.<\/jats:p>","DOI":"10.4049\/jimmunol.1500292","type":"journal-article","created":{"date-parts":[[2016,1,16]],"date-time":"2016-01-16T17:22:33Z","timestamp":1452964953000},"page":"1732-1740","source":"Crossref","is-referenced-by-count":38,"title":["A Novel Factor H\u2013Fc Chimeric Immunotherapeutic Molecule against <i>Neisseria gonorrhoeae<\/i>"],"prefix":"10.1093","volume":"196","author":[{"given":"Jutamas","family":"Shaughnessy","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases and Immunology, 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, University of Massachusetts Medical School , Worcester MA 01605"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarika","family":"Agarwal","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Immunology, University of Massachusetts Medical School , Worcester MA 01605"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magnus","family":"Unemo","sequence":"additional","affiliation":[{"name":"World Health Organization Collaborating Centre for Gonorrhoea and Other Sexually Transmitted Infections, Department of Laboratory Medicine and Microbiology, Orebro University Hospital , SE-701 85 Orebro ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Ohnishi","sequence":"additional","affiliation":[{"name":"National Institute of Infectious Diseases , Tokyo 162-8640 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia-Hong","family":"Su","sequence":"additional","affiliation":[{"name":"Institute of Dermatology, Chinese Academy of Medical Sciences, Peking Union Medical College , Nanjing 210042 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian G","family":"Monks","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Immunology, University of Massachusetts Medical School , Worcester MA 01605"},{"name":"Institute of Innate Immunity, University Hospital, University of Bonn , 53127 Bonn ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2869-5049","authenticated-orcid":false,"given":"Alberto","family":"Visintin","sequence":"additional","affiliation":[{"name":"Centers for Therapeutic Innovation, Pfizer, Inc. , Cambridge, MA 02139"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillermo","family":"Madico","sequence":"additional","affiliation":[{"name":"Section of Infectious Diseases, Boston Medical Center , Boston, MA 02118"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa A","family":"Lewis","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Immunology, University of Massachusetts Medical School , Worcester MA 01605"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas T","family":"Golenbock","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Immunology, University of Massachusetts Medical School , Worcester MA 01605"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George W","family":"Reed","sequence":"additional","affiliation":[{"name":"Preventive and Behavioral Medicine, University of Massachusetts Medical School , Worcester MA 01605"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter A","family":"Rice","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Immunology, 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, University of Massachusetts Medical School , Worcester MA 01605"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2016,2,15]]},"reference":[{"key":"2025030702131857800_r1","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.coph.2014.09.006","article-title":"Update on the antibiotic resistance crisis","volume":"18","author":"Rossolini","year":"2014","journal-title":"Curr. 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