{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T03:29:43Z","timestamp":1773631783497,"version":"3.50.1"},"reference-count":48,"publisher":"American Society for Microbiology","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin. Vaccine Immunol."],"published-print":{"date-parts":[[2011,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Native outer membrane vesicles (NOMV) (not detergent treated), which are prepared from recombinant strains with attenuated endotoxin activity and overexpressed factor H binding protein (fHbp), elicited broad serum bactericidal antibody responses in mice. The amount of overexpressed fHbp required for optimal immunogenicity is not known. In this study we prepared NOMV vaccines from LpxL1 knockout (\u0394LpxL1) mutants with penta-acylated lipooligosaccharide and attenuated endotoxin activity. The recombinant strains had wild-type (1\u00d7) fHbp expression or were engineered for 3-fold- or 10-fold-increased fHbp expression (3\u00d7 or 10\u00d7 fHbp). Control vaccines included NOMV from \u0394LpxL1\/\u0394fHbp mutants or recombinant fHbp. In mice, only the 10\u00d7 fHbp NOMV vaccine elicited significantly higher serum IgG anti-fHbp antibody titers than the corresponding 1\u00d7 fHbp NOMV or recombinant fHbp vaccine. The 10\u00d7 fHbp NOMV vaccine also elicited higher bactericidal responses (<jats:italic>P<\/jats:italic>&lt; 0.05) against five group B strains with heterologous PorA than the recombinant fHbp or 1\u00d7 fHbp NOMV vaccine. The 3\u00d7 fHbp NOMV vaccine gave higher bactericidal titers against only one strain. Serum bactericidal titers in mice immunized with the control \u0394fHbp NOMV vaccines were &lt;1:10, and bactericidal titers in mice immunized with the 10\u00d7 fHbp NOMV vaccine were &lt;1:10 after adsorption of anti-fHbp antibodies. Mixing antiserum to NOMV vaccines from fHbp knockout mutants with antiserum to recombinant fHbp did not increase anti-fHbp bactericidal titers. Thus, a critical threshold of increased fHbp expression is required for NOMV vaccines to elicit broad serum bactericidal responses, and the antibodies conferring protection are directed primarily at fHbp.<\/jats:p>","DOI":"10.1128\/cvi.00542-10","type":"journal-article","created":{"date-parts":[[2011,3,3]],"date-time":"2011-03-03T03:26:21Z","timestamp":1299122781000},"page":"736-742","source":"Crossref","is-referenced-by-count":41,"title":["A Critical Threshold of Meningococcal Factor H Binding Protein Expression Is Required for Increased Breadth of Protective Antibodies Elicited by Native Outer Membrane Vesicle Vaccines"],"prefix":"10.1128","volume":"18","author":[{"given":"Oliver","family":"Koeberling","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabel","family":"Delany","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan M.","family":"Granoff","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","published-online":{"date-parts":[[2011,3,2]]},"reference":[{"key":"key20180919073511_B1","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.1086\/597806","article-title":"Meningococcal factor H-binding protein variants expressed by epidemic capsular group A, W-135, and X strains from Africa","volume":"199","author":"Beernink","year":"2009","journal-title":"J. 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Vaccine Immunol."},{"key":"key20180919073511_B8","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1016\/0264-410X(96)00020-5","article-title":"Production, characterization and control of a Neisseria meningitidis hexavalent class 1 outer membrane protein containing vesicle vaccine","volume":"14","author":"Claassen","year":"1996","journal-title":"Vaccine"},{"key":"key20180919073511_B9","doi-asserted-by":"crossref","first-page":"2483","DOI":"10.1128\/JB.188.7.2483-2492.2006","article-title":"Effect of Neisseria meningitidis fur mutations on global control of gene transcription","volume":"188","author":"Delany","year":"2006","journal-title":"J. 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