Adjuvant effects elicited by novel oligosaccharide variants of detoxified meningococcal lipopolysaccharides on Neisseria meningitidis recombinant PorA protein: a comparison in mice.
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...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4278719?pdf=render |
| _version_ | 1818318374413795328 |
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| author | Ojas H Mehta Gunnstein Norheim J Claire Hoe Christine S Rollier Jerry C Nagaputra Katherine Makepeace Muhammad Saleem Hannah Chan David J P Ferguson Claire Jones Manish Sadarangani Derek W Hood Ian Feavers Jeremy P Derrick Andrew J Pollard E Richard Moxon |
| author_facet | Ojas H Mehta Gunnstein Norheim J Claire Hoe Christine S Rollier Jerry C Nagaputra Katherine Makepeace Muhammad Saleem Hannah Chan David J P Ferguson Claire Jones Manish Sadarangani Derek W Hood Ian Feavers Jeremy P Derrick Andrew J Pollard E Richard Moxon |
| author_sort | Ojas H Mehta |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T09:52:12Z |
| format | Article |
| id | doaj.art-b2f43a6effa2491b81aa811f86a640d7 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T09:52:12Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-b2f43a6effa2491b81aa811f86a640d72022-12-21T23:51:53ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-01912e11571310.1371/journal.pone.0115713Adjuvant effects elicited by novel oligosaccharide variants of detoxified meningococcal lipopolysaccharides on Neisseria meningitidis recombinant PorA protein: a comparison in mice.Ojas H MehtaGunnstein NorheimJ Claire HoeChristine S RollierJerry C NagaputraKatherine MakepeaceMuhammad SaleemHannah ChanDavid J P FergusonClaire JonesManish SadaranganiDerek W HoodIan FeaversJeremy P DerrickAndrew J PollardE Richard MoxonNeisseria 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.http://europepmc.org/articles/PMC4278719?pdf=render |
| spellingShingle | Ojas H Mehta Gunnstein Norheim J Claire Hoe Christine S Rollier Jerry C Nagaputra Katherine Makepeace Muhammad Saleem Hannah Chan David J P Ferguson Claire Jones Manish Sadarangani Derek W Hood Ian Feavers Jeremy P Derrick Andrew J Pollard E Richard Moxon Adjuvant effects elicited by novel oligosaccharide variants of detoxified meningococcal lipopolysaccharides on Neisseria meningitidis recombinant PorA protein: a comparison in mice. PLoS ONE |
| title | Adjuvant effects elicited by novel oligosaccharide variants of detoxified meningococcal lipopolysaccharides on Neisseria meningitidis recombinant PorA protein: a comparison in mice. |
| title_full | Adjuvant effects elicited by novel oligosaccharide variants of detoxified meningococcal lipopolysaccharides on Neisseria meningitidis recombinant PorA protein: a comparison in mice. |
| title_fullStr | Adjuvant effects elicited by novel oligosaccharide variants of detoxified meningococcal lipopolysaccharides on Neisseria meningitidis recombinant PorA protein: a comparison in mice. |
| title_full_unstemmed | Adjuvant effects elicited by novel oligosaccharide variants of detoxified meningococcal lipopolysaccharides on Neisseria meningitidis recombinant PorA protein: a comparison in mice. |
| title_short | Adjuvant effects elicited by novel oligosaccharide variants of detoxified meningococcal lipopolysaccharides on Neisseria meningitidis recombinant PorA protein: a comparison in mice. |
| title_sort | adjuvant effects elicited by novel oligosaccharide variants of detoxified meningococcal lipopolysaccharides on neisseria meningitidis recombinant pora protein a comparison in mice |
| url | http://europepmc.org/articles/PMC4278719?pdf=render |
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