{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T02:27:13Z","timestamp":1779244033461,"version":"3.51.4"},"reference-count":33,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2016,2,1]],"date-time":"2016-02-01T00:00:00Z","timestamp":1454284800000},"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 AI114701"],"award-info":[{"award-number":["R01 AI114701"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01 AI046464"],"award-info":[{"award-number":["R01 AI046464"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2016,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Neisserial surface protein A (NspA) is a highly conserved outer membrane protein previously investigated as a meningococcal vaccine candidate. Despite eliciting serum bactericidal activity in mice, a recombinant NspA vaccine failed to elicit serum bactericidal antibodies in a phase 1 clinical trial in humans. The discordant results may be explained by the recent discovery that NspA is a human-specific ligand of the complement inhibitor factor H (FH). Therefore, in humans but not mice, NspA would be expected to form a complex with FH, which could impair human anti-NspA protective antibody responses. To investigate this question, we immunized human FH transgenic BALB\/c mice with three doses of recombinant NspA expressed in\n            <jats:named-content content-type=\"genus-species\">Escherichia coli<\/jats:named-content>\n            microvesicles, with each dose being separated by 3 weeks. Three of 12 (25%) transgenic mice and 13 of 14 wild-type mice responded with bactericidal titers of \u22651:10 in postimmunization sera (\n            <jats:italic>P<\/jats:italic>\n            = 0.0008, Fisher's exact test). In contrast, human FH transgenic and wild-type mice immunized with a control meningococcal native outer membrane vesicle vaccine had similar serum bactericidal antibody responses directed at PorA, which is not known to bind human FH, and a mutant factor H binding protein (FHbp) antigen with a &gt;50-fold lower level of FH binding than wild-type FHbp antigen binding.Thus, human FH can impair anti-NspA serum bactericidal antibody responses, which may explain the poor immunogenicity of the NspA vaccine previously tested in humans. A mutant NspA vaccine engineered to have decreased binding to human FH may increase protective antibody responses in humans.\n          <\/jats:p>","DOI":"10.1128\/iai.01267-15","type":"journal-article","created":{"date-parts":[[2015,11,24]],"date-time":"2015-11-24T02:59:20Z","timestamp":1448333960000},"page":"452-458","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":14,"title":["Impaired Immunogenicity of Meningococcal Neisserial Surface Protein A in Human Complement Factor H Transgenic Mice"],"prefix":"10.1128","volume":"84","author":[{"given":"Eduardo","family":"Lujan","sequence":"first","affiliation":[{"name":"Center for Immunobiology and Vaccine Development, UCSF Benioff Children's Hospital Oakland Research Institute, Oakland, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rolando","family":"Pajon","sequence":"additional","affiliation":[{"name":"Center for Immunobiology and Vaccine Development, UCSF Benioff Children's Hospital Oakland Research Institute, Oakland, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan M.","family":"Granoff","sequence":"additional","affiliation":[{"name":"Center for Immunobiology and Vaccine Development, UCSF Benioff Children's Hospital Oakland Research Institute, Oakland, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.185.7.1173"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.9.4955-4959.1999"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-1656(00)00294-7"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.63.3.884-890.1995"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1099\/00222615-44-4-237"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0264-410X(93)90045-Y"},{"key":"e_1_3_3_8_2","first-page":"53","volume-title":"Abstr Eleventh Int Pathogenic Neisserial Conf","author":"Danve B","year":"1998","unstructured":"Danve B, Cadoz M, Lissolo L, Boutry E, Guinet F, Speck D, Nassif X, Quentin-Millet M-J. 1998. Safety and immunogenicity of a Neisseria meningitidis group B transferrin binding protein vaccine in adults, p 53. Abstr Eleventh Int Pathogenic Neisserial Conf, Nice, France. http:\/\/neisseria.org\/ipnc\/1998\/Abstracts_Neisseria98.pdf."},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2006.08.001"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1001027"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00781-07"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1003470"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.02572-14"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01625-14"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.71.12.6844-6849.2003"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.11.5664-5675.1999"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0066536"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2008.01955.x"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2006.09.016"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00103-12"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.00542-10"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.69.6.3762-3771.2001"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.11.6021-6031.2002"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.05182-11"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2010.12.075"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.00474-15"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002688"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1086\/589308"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.00260-13"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiv081"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0128185"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2013.08.099"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2014.03.068"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2011.04.095"}],"container-title":["Infection and Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.01267-15","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.01267-15","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,5]],"date-time":"2022-03-05T10:11:09Z","timestamp":1646475069000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/IAI.01267-15"}},"subtitle":[],"editor":[{"given":"L.","family":"Pirofski","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2016,2]]},"references-count":33,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2016,2]]}},"alternative-id":["10.1128\/IAI.01267-15"],"URL":"https:\/\/doi.org\/10.1128\/iai.01267-15","relation":{},"ISSN":["0019-9567","1098-5522"],"issn-type":[{"value":"0019-9567","type":"print"},{"value":"1098-5522","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,2]]},"assertion":[{"value":"2015-10-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-11-14","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-01-25","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}