Neisseria meningitidis Native Outer Membrane Vesicles Containing Different Lipopolysaccharide Glycoforms as Adjuvants for Meningococcal and Nonmeningococcal Antigens
Neisseria meningitidis Native Outer Membrane Vesicles Containing Different Lipopolysaccharide Glycoforms as Adjuvants for Meningococcal and Nonmeningococcal Antigens
复制标题
DOI：
10.1128/cvi.00561-13
复制
发表时间：
2013-12
影响因子：
--
通讯作者：
J. Nagaputra;C. Rollier;M. Sadarangani;J. C. Hoe;Ojas H. Mehta;G. Norheim;M. Saleem;H. Chan
中科院分区：
文献类型：
--
作者：
J. Nagaputra;C. Rollier;M. Sadarangani;J. C. Hoe;Ojas H. Mehta;G. Norheim;M. Saleem;H. Chan
我们评价了脂多糖（LPS）的修饰糖型（LgtB-LpxL 1）与未修饰糖型LpxL 1血清群B脑膜炎球菌H44/76天然外膜囊泡（nOMV）对重组脑膜炎球菌蛋白、rPorA、破伤风类毒素或脑膜炎球菌血清群C荚膜多糖疫苗接种的免疫应答的佐剂效应。我们使用LgtB-LpxL 1 LPS，因为已显示lgtB基因的破坏（其导致LPS外核中的N-乙酰葡糖胺-半乳糖-葡萄糖残基的暴露）增强体外人树突细胞的活化。将反应与基于单磷酰脂质A（MPL）的佐剂和氢氧化铝悬浮液的反应进行比较。nOMV诱导的针对三种抗原中的每一种的血清IgG应答与用MPL或铝盐获得的那些相当。然而，nOMV引起（i）针对rPorA的较低IgG 1/IgG 2a比率和（ii）血清杀菌抗体滴度上级于用铝盐获得的那些，达到与用MPL获得的那些相似的滴度。类似地，通过用脑膜炎球菌血清群C多糖和nOMV免疫诱导的杀菌抗体滴度与使用MPL获得的那些相似，但优于用铝盐获得的那些。用破伤风类毒素和nOMV免疫导致破伤风类毒素特异性IgG应答类似于用铝盐佐剂时获得的那些。这些结果突出了脑膜炎球菌LpxL 1 LPS含有的nOMV作为重组脑膜炎球菌蛋白疫苗的佐剂的潜在效用，并表明它们可能与各种其他抗原一起使用。
ABSTRACT 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.