{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T23:41:21Z","timestamp":1793835681199,"version":"4.6.1"},"reference-count":47,"publisher":"Frontiers Media SA","content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"DOI":"10.3389\/fimmu.2016.00562","type":"journal-article","created":{"date-parts":[[2016,12,8]],"date-time":"2016-12-08T10:21:24Z","timestamp":1481192484000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":30,"title":["A Meningococcal Outer Membrane Vesicle Vaccine Incorporating Genetically Attenuated Endotoxin Dissociates Inflammation from Immunogenicity"],"prefix":"10.3389","volume":"7","author":[{"given":"David J.","family":"Dowling","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holly","family":"Sanders","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wing Ki","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sweta","family":"Joshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Spencer","family":"Brightman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilana","family":"Bergelson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Pietrasanta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon D.","family":"van Haren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"van Amsterdam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Fernandez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Germie P. J. M.","family":"van den Dobbelsteen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ofer","family":"Levy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2016,12,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1038\/ni0311-189","article-title":"Challenges in infant immunity: implications for responses to infection and vaccines","volume":"12","author":"Prabhudas","year":"2011","journal-title":"Nat Immunol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1016\/j.it.2014.04.007","article-title":"Ontogeny of early life immunity","volume":"35","author":"Dowling","year":"2014","journal-title":"Trends Immunol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1395","DOI":"10.1097\/INF.0000000000000893","article-title":"Pediatric vaccine adjuvants: components of the modern vaccinologist\u2019s toolbox","volume":"34","author":"Dowling","year":"2015","journal-title":"Pediatr Infect Dis J"},{"key":"B4","volume-title":"Vaccines","author":"Plotkin","year":"2012","edition":"Sixth ed"},{"key":"B5","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1136\/archdischild-2015-308928","article-title":"Enter B and W: two new meningococcal vaccine programmes launched","volume":"101","author":"Ladhani","year":"2016","journal-title":"Arch Dis Child"},{"key":"B6","doi-asserted-by":"publisher","first-page":"426","DOI":"10.1016\/S1473-3099(13)70341-4","article-title":"A vaccine against serogroup B Neisseria meningitidis: dealing with uncertainty","volume":"14","author":"Andrews","year":"2014","journal-title":"Lancet Infect Dis"},{"key":"B7","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1586\/erv.12.137","article-title":"Preclinical evaluation of MenB vaccines: prerequisites for clinical development","volume":"12","author":"Sanders","year":"2013","journal-title":"Expert Rev Vaccines"},{"issue":"Suppl 2","key":"B8","doi-asserted-by":"publisher","first-page":"B87","DOI":"10.1016\/j.vaccine.2012.01.033","article-title":"The new multicomponent vaccine against meningococcal serogroup B, 4CMenB: immunological, functional and structural characterization of the antigens","volume":"30","author":"Serruto","year":"2012","journal-title":"Vaccine"},{"key":"B9","first-page":"67","article-title":"Production, characterization and control of MenB-vaccine \u201cFolkehelsa\u201d: an outer membrane vesicle vaccine against group B meningococcal disease","volume":"14","author":"Fredriksen","year":"1991","journal-title":"NIPH Ann"},{"key":"B10","volume-title":"Annex I \u2013 Summary of Product Characteristics","author":"CHMP","year":"2015"},{"key":"B11","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1097\/INF.0000000000000917","article-title":"Severe upper extremity dysfunction after 4CMenB vaccination in a young infant","volume":"35","author":"Tenenbaum","year":"2016","journal-title":"Pediatr Infect Dis J"},{"key":"B12","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1016\/S0140-6736(12)61961-8","article-title":"Immunogenicity and safety of an investigational multicomponent, recombinant, meningococcal serogroup B vaccine (4CMenB) administered concomitantly with routine infant and child vaccinations: results of two randomised trials","volume":"381","author":"Vesikari","year":"2013","journal-title":"Lancet"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1993","DOI":"10.4161\/hv.28666","article-title":"A phase 2 randomized controlled trial of a multicomponent meningococcal serogroup B vaccine (I)","volume":"10","author":"Prymula","year":"2014","journal-title":"Hum Vaccin Immunother"},{"key":"B14","doi-asserted-by":"publisher","first-page":"47","DOI":"10.14573\/altex.1509291","article-title":"Limitations of the rabbit pyrogen test for assessing meningococcal OMV based vaccines","volume":"33","author":"Vipond","year":"2016","journal-title":"ALTEX"},{"key":"B15","doi-asserted-by":"publisher","first-page":"5981","DOI":"10.1128\/IAI.69.10.5981-5990.2001","article-title":"Modification of lipid A biosynthesis in Neisseria meningitidis lpxL mutants: influence on lipopolysaccharide structure, toxicity, and adjuvant activity","volume":"69","author":"Van Der Ley","year":"2001","journal-title":"Infect Immun"},{"key":"B16","doi-asserted-by":"publisher","first-page":"4810","DOI":"10.1016\/j.vaccine.2010.04.082","article-title":"Improved OMV vaccine against Neisseria meningitidis using genetically engineered strains and a detergent-free purification process","volume":"28","author":"Van De Waterbeemd","year":"2010","journal-title":"Vaccine"},{"key":"B17","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1016\/j.cyto.2007.11.020","article-title":"A comparative analysis of cytokine responses, cell surface marker expression and MAPKs in DCs matured with LPS compared with a panel of TLR ligands","volume":"41","author":"Dowling","year":"2008","journal-title":"Cytokine"},{"key":"B18","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1111\/j.1462-5822.2005.00623.x","article-title":"Neisseria meningitidis expressing lgtB lipopolysaccharide targets DC-SIGN and modulates dendritic cell function","volume":"8","author":"Steeghs","year":"2006","journal-title":"Cell Microbiol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"457","DOI":"10.3389\/fimmu.2014.00457","article-title":"Soluble mediators regulating immunity in early life","volume":"5","author":"Pettengill","year":"2014","journal-title":"Front Immunol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1284","DOI":"10.1016\/j.cell.2012.02.012","article-title":"Beyond empiricism: informing vaccine development through innate immunity research","volume":"148","author":"Levitz","year":"2012","journal-title":"Cell"},{"key":"B21","doi-asserted-by":"publisher","first-page":"458","DOI":"10.1016\/j.biologicals.2013.08.006","article-title":"Predictive markers of safety and immunogenicity of adjuvanted vaccines","volume":"41","author":"Mastelic","year":"2013","journal-title":"Biologicals"},{"key":"B22","doi-asserted-by":"publisher","first-page":"909406","DOI":"10.1155\/2015\/909406","article-title":"Application of \u201csystems vaccinology\u201d to evaluate inflammation and reactogenicity of adjuvanted preventative vaccines","volume":"2015","author":"Lewis","year":"2015","journal-title":"J Immunol Res"},{"key":"B23","doi-asserted-by":"publisher","first-page":"e58164","DOI":"10.1371\/journal.pone.0058164","article-title":"The ultra-potent and selective TLR8 agonist VTX-294 activates human newborn and adult leukocytes","volume":"8","author":"Dowling","year":"2013","journal-title":"PLoS One"},{"issue":"195\u2013204","key":"B24","doi-asserted-by":"publisher","first-page":"e199","DOI":"10.1016\/j.jaci.2012.02.042","article-title":"Imidazoquinoline toll-like receptor 8 agonists activate human newborn monocytes and dendritic cells through adenosine-refractory and caspase-1-dependent pathways","volume":"130","author":"Philbin","year":"2012","journal-title":"J Allergy Clin Immunol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"8876","DOI":"10.1016\/j.biomaterials.2014.06.043","article-title":"The effect of stable macromolecular complexes of ionic polyphosphazene on HIV Gag antigen and on activation of human dendritic cells and presentation to T-cells","volume":"35","author":"Palmer","year":"2014","journal-title":"Biomaterials"},{"key":"B26","doi-asserted-by":"publisher","first-page":"e0134640","DOI":"10.1371\/journal.pone.0134640","article-title":"The imidazoquinoline toll-like receptor-7\/8 agonist hybrid-2 potently induces cytokine production by human newborn and adult leukocytes","volume":"10","author":"Ganapathi","year":"2015","journal-title":"PLoS One"},{"key":"B27","doi-asserted-by":"publisher","first-page":"e65157","DOI":"10.1371\/journal.pone.0065157","article-title":"Improved production process for native outer membrane vesicle vaccine against Neisseria meningitidis","volume":"8","author":"Van De Waterbeemd","year":"2013","journal-title":"PLoS One"},{"key":"B28","volume-title":"Investigation of the Potential of PorA and FetA as Meningococcal Vaccine Components","author":"Sanders","year":"2012"},{"key":"B29","doi-asserted-by":"publisher","first-page":"3762","DOI":"10.1016\/j.vaccine.2005.02.021","article-title":"Development and characterisation of outer membrane vesicle vaccines against serogroup A Neisseria meningitidis","volume":"23","author":"Norheim","year":"2005","journal-title":"Vaccine"},{"key":"B30","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1128\/CDLI.4.2.156-167.1997","article-title":"Standardization and a multilaboratory comparison of Neisseria meningitidis serogroup A and C serum bactericidal assays. The Multilaboratory Study Group","volume":"4","author":"Maslanka","year":"1997","journal-title":"Clin Diagn Lab Immunol"},{"issue":"6","key":"B31","doi-asserted-by":"publisher","first-page":"1877","DOI":"10.1074\/mcp.M115.055541","article-title":"Adjuvant-induced human monocyte secretome profiles reveal adjuvant- and age-specific protein signatures","volume":"15","author":"Oh","year":"2016","journal-title":"Mol Cell Proteomics"},{"key":"B32","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/j.cyto.2016.04.001","article-title":"In vitro cytokine induction by TLR-activating vaccine adjuvants in human blood varies by age and adjuvant","volume":"83","author":"Van Haren","year":"2016","journal-title":"Cytokine"},{"key":"B33","doi-asserted-by":"publisher","first-page":"4859","DOI":"10.1016\/j.vaccine.2012.05.002","article-title":"Use of human MonoMac6 cells for development of in vitro assay predictive of adjuvant safety in vivo","volume":"30","author":"Zaitseva","year":"2012","journal-title":"Vaccine"},{"key":"B34","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1038\/nri2868","article-title":"Vaccine delivery: a matter of size, geometry, kinetics and molecular patterns","volume":"10","author":"Bachmann","year":"2010","journal-title":"Nat Rev Immunol"},{"key":"B35","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1086\/589308","article-title":"Bactericidal antibody responses elicited by a meningococcal outer membrane vesicle vaccine with overexpressed factor H-binding protein and genetically attenuated endotoxin","volume":"198","author":"Koeberling","year":"2008","journal-title":"J Infect Dis"},{"key":"B36","doi-asserted-by":"publisher","first-page":"3801","DOI":"10.1128\/IAI.00005-08","article-title":"Differential activation of human and mouse toll-like receptor 4 by the adjuvant candidate LpxL1 of Neisseria meningitidis","volume":"76","author":"Steeghs","year":"2008","journal-title":"Infect Immun"},{"key":"B37","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1128\/CVI.00403-08","article-title":"Meningococcal outer membrane vesicle vaccines derived from mutant strains engineered to express factor H binding proteins from antigenic variant groups 1 and 2","volume":"16","author":"Koeberling","year":"2009","journal-title":"Clin Vaccine Immunol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"3177","DOI":"10.1128\/IAI.01311-09","article-title":"The structure of Neisseria meningitidis lipid A determines outcome in experimental meningococcal disease","volume":"78","author":"Fransen","year":"2010","journal-title":"Infect Immun"},{"key":"B39","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1128\/CVI.00342-09","article-title":"Evaluation of a whole-blood cytokine release assay for use in measuring endotoxin activity of group B Neisseria meningitidis vaccines made from lipid A acylation mutants","volume":"17","author":"Stoddard","year":"2010","journal-title":"Clin Vaccine Immunol"},{"key":"B40","doi-asserted-by":"publisher","first-page":"4728","DOI":"10.1016\/j.vaccine.2011.04.095","article-title":"Immunogenicity of a meningococcal native outer membrane vesicle vaccine with attenuated endotoxin and over-expressed factor H binding protein in infant rhesus monkeys","volume":"29","author":"Koeberling","year":"2011","journal-title":"Vaccine"},{"key":"B41","doi-asserted-by":"publisher","first-page":"e0148840","DOI":"10.1371\/journal.pone.0148840","article-title":"Impact of reducing complement inhibitor binding on the immunogenicity of native Neisseria meningitidis outer membrane vesicles","volume":"11","author":"Daniels-Treffandier","year":"2016","journal-title":"PLoS One"},{"key":"B42","doi-asserted-by":"publisher","first-page":"1413","DOI":"10.1016\/j.vaccine.2010.12.039","article-title":"A phase 1 study of a meningococcal native outer membrane vesicle vaccine made from a group B strain with deleted lpxL1 and synX, over-expressed factor H binding protein, two PorAs and stabilized OpcA expression","volume":"29","author":"Keiser","year":"2011","journal-title":"Vaccine"},{"key":"B43","doi-asserted-by":"publisher","first-page":"7150","DOI":"10.4049\/jimmunol.0901481","article-title":"Neonatal innate TLR-mediated responses are distinct from those of adults","volume":"183","author":"Kollmann","year":"2009","journal-title":"J Immunol"},{"key":"B44","doi-asserted-by":"publisher","first-page":"e44763","DOI":"10.1371\/journal.pone.0044763","article-title":"Ontogeny of toll-like receptor mediated cytokine responses of South African infants throughout the first year of life","volume":"7","author":"Reikie","year":"2012","journal-title":"PLoS One"},{"key":"B45","doi-asserted-by":"publisher","first-page":"e18185","DOI":"10.1371\/journal.pone.0018185","article-title":"Age-dependent maturation of toll-like receptor-mediated cytokine responses in Gambian infants","volume":"6","author":"Burl","year":"2011","journal-title":"PLoS One"},{"key":"B46","doi-asserted-by":"publisher","first-page":"8668","DOI":"10.1074\/jbc.M114.554345","article-title":"Lipopolysaccharide engineering in Neisseria meningitidis: structural analysis of different pentaacyl lipid A mutants and comparison of their modified agonist properties","volume":"289","author":"Pupo","year":"2014","journal-title":"J Biol Chem"},{"key":"B47","doi-asserted-by":"publisher","first-page":"2151","DOI":"10.1016\/S0140-6736(12)60560-1","article-title":"Global, regional, and national causes of child mortality: an updated systematic analysis for 2010 with time trends since 2000","volume":"379","author":"Liu","year":"2012","journal-title":"Lancet"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"http:\/\/journal.frontiersin.org\/article\/10.3389\/fimmu.2016.00562\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,9,27]],"date-time":"2020-09-27T20:37:43Z","timestamp":1601239063000},"score":1,"resource":{"primary":{"URL":"http:\/\/journal.frontiersin.org\/article\/10.3389\/fimmu.2016.00562\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,12,8]]},"references-count":47,"URL":"https:\/\/doi.org\/10.3389\/fimmu.2016.00562","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,12,8]]}}}