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解毒的脑膜炎奈瑟菌脂多糖新型寡糖变体对脑膜炎奈瑟菌重组PorA蛋白的佐剂效应:小鼠体内的比较

Adjuvant effects elicited by novel oligosaccharide variants of detoxified meningococcal lipopolysaccharides on Neisseria meningitidis recombinant PorA protein: a comparison in mice.

作者信息

Mehta Ojas H, Norheim Gunnstein, Hoe J Claire, Rollier Christine S, Nagaputra Jerry C, Makepeace Katherine, Saleem Muhammad, Chan Hannah, Ferguson David J P, Jones Claire, Sadarangani Manish, Hood Derek W, Feavers Ian, Derrick Jeremy P, Pollard Andrew J, Moxon E Richard

机构信息

Oxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Biomedical Research Centre, Churchill Hospital, Headington, Oxford, OX3 7LE, United Kingdom.

Faculty of Life Sciences, The University of Manchester, Michael Smith Building, Oxford Road, Manchester, M139PT, United Kingdom.

出版信息

PLoS One. 2014 Dec 29;9(12):e115713. doi: 10.1371/journal.pone.0115713. eCollection 2014.

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.

摘要

脑膜炎奈瑟菌脂多糖(LPS)具有佐剂特性,可用于增强疫苗的免疫原性。修饰的五酰化LPS保留了六酰化LPS的佐剂特性,但毒性有所降低。在本研究中,我们调查了与先前描述的LgtB变体相比,解毒五酰化LPS的两种修饰糖型结构(LgtE和IcsB)在配制成天然外膜囊泡(nOMV)时是否表现出不同的佐剂特性。通过破坏lpxL1基因获得解毒五酰化LPS(LpxL1 LPS),并分别通过破坏lgtB、lgtE或icsB基因获得三种不同的糖型。用重组PorA P1.7-2,4(rPorA)蛋白与不同的nOMV(含有不同的PorA血清亚型P1.7,16)共同免疫小鼠(小家鼠),每个nOMV表达三种五酰化LPS糖型之一。所有nOMV均诱导了针对rPorA的IgG反应,但与其他nOMV或使用氢氧化铝佐剂时相比,含有五酰化LgtB-LpxL1 LPS糖型的nOMV诱导的杀菌活性显著更高。与LgtE或IcsB LPS糖型相比,这些数据支持使用含有解毒、修饰的LgtB-LpxL1 LPS的nOMV作为未来脑膜炎球菌蛋白疫苗的潜在佐剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60f3/4278719/38d3b2e77b2f/pone.0115713.g001.jpg

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