title: Adjuvant effects elicited by novel oligosaccharide variants of detoxified meningococcal lipopolysaccharides on Neisseria meningitidis recombinant PorA protein: a comparison in mice.
abstract: Neisseria meningitidis lipopolysaccharide (LPS) has adjuvant properties that can be exploited to assist vaccine immunogenicity. The modified penta-acylated LPS retains the adjuvant properties of hexa-acylated LPS but has a reduced toxicity profile. In this study we investigated whether two modified glycoform structures (LgtE and IcsB) of detoxified penta-acylated LPS exhibited differential adjuvant properties when formulated as native outer membrane vesicles (nOMVs) as compared to the previously described LgtB variant. Detoxified penta-acylated LPS was obtained by disruption of the lpxL1 gene (LpxL1 LPS), and three different glycoforms were obtained by disruption of the lgtB, lgtE or icsB genes respectively. Mice (mus musculus) were immunized with a recombinant PorA P1.7-2,4 (rPorA) protein co-administered with different nOMVs (containing a different PorA serosubtype P1.7,16), each of which expressed one of the three penta-acylated LPS glycoforms. All nOMVs induced IgG responses against the rPorA, but the nOMVs containing the penta-acylated LgtB-LpxL1 LPS glycoform induced significantly greater bactericidal activity compared to the other nOMVs or when the adjuvant was Alhydrogel. Compared to LgtE or IcsB LPS glycoforms, these data support the use of nOMVs containing detoxified, modified LgtB-LpxL1 LPS as a potential adjuvant for future meningococcal protein vaccines.
authors.affiliation: Oxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Biomedical Research Centre, Churchill Hospital, Headington, Oxford, OX3 7LE, United Kingdom.
authors.forename: Ojas H
authors.initials: OH
authors.lastname: Mehta
authors.affiliation: Oxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Biomedical Research Centre, Churchill Hospital, Headington, Oxford, OX3 7LE, United Kingdom.
authors.forename: Gunnstein
authors.initials: G
authors.lastname: Norheim
authors.affiliation: Oxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Biomedical Research Centre, Churchill Hospital, Headington, Oxford, OX3 7LE, United Kingdom.
authors.forename: J Claire
authors.initials: JC
authors.lastname: Hoe
authors.affiliation: Oxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Biomedical Research Centre, Churchill Hospital, Headington, Oxford, OX3 7LE, United Kingdom.
authors.forename: Christine S
authors.initials: CS
authors.lastname: Rollier
authors.affiliation: Oxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Biomedical Research Centre, Churchill Hospital, Headington, Oxford, OX3 7LE, United Kingdom.
authors.forename: Jerry C
authors.initials: JC
authors.lastname: Nagaputra
authors.affiliation: Oxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Biomedical Research Centre, Churchill Hospital, Headington, Oxford, OX3 7LE, United Kingdom.
authors.forename: Katherine
authors.initials: K
authors.lastname: Makepeace
authors.affiliation: Faculty of Life Sciences, The University of Manchester, Michael Smith Building, Oxford Road, Manchester, M139PT, United Kingdom.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Saleem
authors.affiliation: Division of Bacteriology, National Institute of Biological Standards and Control, Blanche Lane, South Mimms, Potters Bar, Hertfordshire, EN6 3OG, United Kingdom.
authors.forename: Hannah
authors.initials: H
authors.lastname: Chan
authors.affiliation: Nuffield Department of Clinical Laboratory Sciences, University of Oxford, Oxford, United Kingdom.
authors.forename: David J P
authors.initials: DJ
authors.lastname: Ferguson
authors.affiliation: Oxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Biomedical Research Centre, Churchill Hospital, Headington, Oxford, OX3 7LE, United Kingdom.
authors.forename: Claire
authors.initials: C
authors.lastname: Jones
authors.affiliation: Oxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Biomedical Research Centre, Churchill Hospital, Headington, Oxford, OX3 7LE, United Kingdom.
authors.forename: Manish
authors.initials: M
authors.lastname: Sadarangani
authors.affiliation: Department of Paediatrics, Children's Hospital (John Radcliffe), Headley Way, Headington, Oxford, OX3 9DU, United Kingdom.
authors.forename: Derek W
authors.initials: DW
authors.lastname: Hood
authors.affiliation: Division of Bacteriology, National Institute of Biological Standards and Control, Blanche Lane, South Mimms, Potters Bar, Hertfordshire, EN6 3OG, United Kingdom.
authors.forename: Ian
authors.initials: I
authors.lastname: Feavers
authors.affiliation: Faculty of Life Sciences, The University of Manchester, Michael Smith Building, Oxford Road, Manchester, M139PT, United Kingdom.
authors.forename: Jeremy P
authors.initials: JP
authors.lastname: Derrick
authors.affiliation: Oxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Biomedical Research Centre, Churchill Hospital, Headington, Oxford, OX3 7LE, United Kingdom.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Pollard
authors.affiliation: The NIHR Oxford Biomedical Research Centre, Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, Headington, Oxford, OX3 7LE, United Kingdom.
authors.forename: E Richard
authors.initials: ER
authors.lastname: Moxon
mesh_terms: D056704:Adaptive Immunity / Q000187:drug effects*; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D005260:Female; D007114:Immunization; D008070:Lipopolysaccharides / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology; D008815:Mice, Inbred Strains; D009154:Mutation; D009345:Neisseria meningitidis / Q000235:genetics / Q000276:immunology*; D009844:Oligosaccharides / Q000737:chemistry* / Q000494:pharmacology; D018272:Porins / Q000737:chemistry / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D008070:Lipopolysaccharides; D009844:Oligosaccharides; D018272:Porins; D011994:Recombinant Proteins; C057699:porin protein, Neisseria