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首页> 外文期刊>Vaccine >Immunogenic display of diverse peptides, including a broadly cross-type neutralizing human papillomavirus L2 epitope, on virus-like particles of the RNA bacteriophage PP7
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Immunogenic display of diverse peptides, including a broadly cross-type neutralizing human papillomavirus L2 epitope, on virus-like particles of the RNA bacteriophage PP7

机译:在RNA噬菌体PP7的病毒样颗粒上免疫原性展示多种肽,包括广泛交叉型的中和人乳头瘤病毒L2表位

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摘要

The immunogenicity of an antigen can be dramatically increased by displaying it in a dense, multivalent context, such as on the surface of a virus or virus-like particle (VLP). Here we describe a highly versatile VLP platform for peptide display based on VLPs of the RNA bacteriophage PP7. We show that this platform can be used for the engineered display of specific peptide sequences as well as for the construction of random peptide libraries. Peptides representing the FLAG epitope, the V3 loop of HIV gp120, and a broadly cross-type neutralizing epitope from L2, the minor capsid protein of Human Papillomavirus type 16 (HPV16), were inserted into an exposed surface loop of a form of PP7 coat protein in which the two identical polypeptides of coat were fused together to form a single-chain dimer. The recombinant proteins assembled into VLPs, displayed these peptides on their surfaces, and induced high-titer antibody responses. The single-chain dimer was also highly tolerant of random 6-, 8-, and 10-amino acid insertions. PP7 VLPs displaying the HPV16 L2 epitope generated robust anti-HPV16 L2 serum antibodies after intramuscular injection that protected mice from genital infection with HPV16 pseudovirus as well as a heterologous HPV pseudovirus type, HPV45. Thus, PP7 VLPs are well-suited for the display of a wide diversity of peptides in a highly immunogenic format.
机译:通过在致密,多价的环境中(例如在病毒或病毒样颗粒(VLP)的表面)展示抗原,可以显着提高抗原的免疫原性。在这里,我们描述了一种基于RNA噬菌体PP7的VLP的肽展示的多功能VLP平台。我们显示该平台可用于特定肽序列的工程展示以及随机肽库的构建。将代表FLAG表位,HIV gp120的V3环和来自L2的广泛交叉型中和表位的肽(人乳头瘤病毒16型的次要衣壳蛋白(HPV16))插入到暴露的PP7涂层形式的表面环中一种蛋白质,其中外壳的两个相同多肽融合在一起形成单链二聚体。重组蛋白组装成VLP,在其表面展示这些肽,并诱导高滴度抗体应答。单链二聚体也高度耐受随机6-,8-和10-氨基酸插入。展示HPV16 L2表位的PP7 VLP在肌肉注射后产生了强大的抗HPV16 L2血清抗体,可保护小鼠免受生殖器感染HPV16假病毒以及异源HPV假病毒HPV45。因此,PP7 VLP非常适合以高度免疫原性的形式展示多种肽。

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