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首页> 外文期刊>Clinical and vaccine immunology: CVI >Neisseria meningitidis Native Outer Membrane Vesicles Containing Different Lipopolysaccharide Glycoforms as Adjuvants for Meningococcal and Nonmeningococcal Antigens
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Neisseria meningitidis Native Outer Membrane Vesicles Containing Different Lipopolysaccharide Glycoforms as Adjuvants for Meningococcal and Nonmeningococcal Antigens

机译：脑膜炎奈瑟氏球菌天然外膜囊泡，含有不同的脂多糖糖形式作为脑膜炎球菌和非脑膜炎球菌抗原的佐剂

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We evaluated the adjuvant effect of a modified glycoform of lipopolysaccharide (LPS) (LgtB-LpxL1) compared to that of the nonmodified glycoform Lpxl1 serogroup B meningococcal H44/76 native outer membrane vesicles (nOMVs) on immune responses to vaccination with the recombinant meningococcal protein, rPorA, tetanus toxoid, or meningococcal serogroup C capsular polysaccharide. We used LgtB-LpxL1 LPS because the disruption of the lgtB gene, which results in the exposure of N-acetylglucosamine-galactose-glucose residues in the LPS outer core, has been shown to enhance the activation of human dendritic cells in vitro. The responses were compared to those of a monophosphoryl lipid A (MPL)-based adjuvant and to an aluminum hydroxide suspension. The nOMVs induced blood serum IgG responses against each of the three antigens comparable to those obtained with MPL or aluminum salt. However, nOMVs elicited (i) a lower IgG1/IgG2a ratio against rPorA and (ii) serum bactericidal antibody titers superior to those achieved with aluminum salt, reaching similar titers to those obtained with MPL. Similarly, bactericidal antibody titers induced by immunization with meningococcal serogroup C polysaccharide and nOMVs were similar to those obtained using MPL but were better than those with aluminum salt. Immunization with tetanus toxoid and nOMVs resulted in tetanus toxoid-specific IgG responses similar to those obtained when adjuvanted with aluminum salt. These results highlight the potential utility of meningococcal LpxL1 LPS-containing nOMVs as an adjuvant for recombinant meningococcal protein vaccines and suggest their possible use with a variety of other antigens.
机译：我们评估了脂多糖（LPS）（LgtB-LpxL1）的修饰糖形式与未修饰的糖形式Lpxl1 B群脑膜炎球菌H44 / 76天然外膜囊泡（nOMVs）相比对重组脑膜炎球菌疫苗免疫反应的佐剂作用，rPorA，破伤风类毒素或脑膜炎球菌C群血清荚膜多糖。我们使用LgtB-LpxL1 LPS是因为 lgtB 基因的破坏（导致了LPS外核中 N -乙酰氨基葡萄糖-半乳糖-葡萄糖残基的暴露）被破坏。证明可以增强人树突状细胞的体外激活。将响应与基于单磷酰脂质A（MPL）的佐剂和氢氧化铝悬浮液的响应进行了比较。与用MPL或铝盐获得的抗原相比，nOMV诱导的针对三种抗原的血清IgG反应。但是，nOMV引起（i）相对于rPorA的IgG1 / IgG2a比率较低，以及（ii）血清杀菌抗体的效价优于铝盐，与MPL的效价相似。同样，通过脑膜炎球菌C群血清多糖和nOMV免疫诱导的杀菌抗体效价与使用MPL获得的抗体相似，但优于使用铝盐的抗体。用破伤风类毒素和nOMV免疫可导致破伤风类毒素特异性IgG反应，与铝盐佐剂相似。这些结果突出了含脑膜炎球菌LpxL1 LPS的nOMV作为重组脑膜炎球菌蛋白疫苗佐剂的潜在用途，并暗示了它们可能与多种其他抗原一起使用。

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