Selection and characterization of cyclic peptides that bind to a monoclonal antibody against meningococcal L3,7,9 lipopolysaccharides
Selection and characterization of cyclic peptides that bind to a monoclonal antibody against meningococcal L3,7,9 lipopolysaccharides
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DOI：
10.1111/j.1365-3083.2004.01400.x
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发表时间：
2004-04-01
影响因子：
3.7
通讯作者：
Michaelsen, TE
中科院分区：
文献类型：
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作者：
Lauvrak, V;Berntzen, G;Michaelsen, TE
目前仍没有预防b群脑膜炎球菌菌株引起的疾病的通用疫苗。脑膜炎球菌脂多糖（lps）作为潜在的候选疫苗已受到关注，但对其安全性的担忧也有所提高。LPS表位的肽模拟物可能是LPS免疫的安全替代品。单克隆抗体（MoAb） 9-2-L3,7,9[1]特异性针对脑膜炎奈瑟菌LPS免疫型L3,7,9具有杀菌作用，不与人体组织发生交叉反应。为了探索从MoAb 9-2- l3,7,9识别的表位中分离肽模拟物的可能性，我们构建了两个噬菌体展示文库，分别由6个和9个随机氨基酸组成，两侧为半胱氨酸。此外，我们开发了一个系统，用于从噬菌体展示系统到乙型肝炎核心（HBc）表达系统的肽编码序列的简单交换。在与lps结合位点重叠的位点上特异性结合MoAb 9-2- l3、7,9的环状肽从两个文库中选择。与MoAb 9-2- l3、7、9反应的四种测试肽中有三种成功地融合到大肠杆菌中表达的HBc颗粒的免疫优势环中。然而，锁孔帽贝血青素和HBc颗粒融合的肽偶联物在小鼠中均未能产生抗lps反应。
There is still no general vaccine for prevention of disease caused by group-B meningococcal strains. Meningococcal lipopolysaccharides (LPSs) have received attention as potential vaccine candidates, but concerns regarding their safety have been raised. Peptide mimics of LPS epitopes may represent safe alternatives to immunization with LPS. The monoclonal antibody (MoAb) 9-2-L3,7,9 [1] specific for Neisseria meningitidis LPS immunotype L3,7,9 is bactericidal and does not cross-react with human tissue. To explore the possibility of isolating peptide mimics of the epitope recognized by MoAb 9-2-L3,7,9, we have constructed two phage display libraries of six and nine random amino acids flanked by cysteines. Furthermore, we developed a system for the easy exchange of peptide-encoding sequences from the phage-display system to a hepatitis B core (HBc) expression system. Cyclic peptides that specifically bound MoAb 9-2-L3,7,9 at a site overlapping with the LPS-binding site were selected from both libraries. Three out of four tested peptides which reacted with MoAb 9-2-L3,7,9 were successfully presented as fusions to the immunodominant loop of HBc particles expressed in Escherichia coli. However, both peptide conjugates to keyhole limpet haemocyanin and HBc particle fusions failed to give an anti-LPS response in mice.