Immunogenic display of diverse peptides, including a broadly cross-type neutralizing human papillomavirus L2 epitope, on virus-like particles of the RNA bacteriophage PP7
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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DOI：
10.1016/j.vaccine.2010.04.049
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发表时间：
2010-06-17
期刊：
影响因子：
5.5
通讯作者：
Peabody, David S.
中科院分区：
文献类型：
--
作者：
Caldeira, Jerri do Carmo;Medford, Alexander;Peabody, David S.
抗原的免疫原性可以通过在密集的、多价的环境中显示，例如在病毒或病毒样颗粒（VLP）的表面上显示而显著增加。在这里，我们描述了一个基于RNA噬菌体PP7的VLPs的高度通用的肽展示VLP平台。我们证明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。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（人类乳头瘤病毒16型（HPV16）的次要衣壳蛋白）被插入PP7外壳蛋白形式的暴露表面环中，其中两个相同的外壳多肽融合在一起形成单链二聚体。重组蛋白组装成VLPs，在其表面显示这些肽，并诱导高滴度抗体反应。单链二聚体对随机插入的6-、8-和10-氨基酸也具有高度的耐受性。显示HPV16 L2表位的PP7 VLPs在肌肉注射后产生强大的抗HPV16 L2血清抗体，保护小鼠免受HPV16假病毒和异源HPV假病毒HPV45的生殖器感染。因此，PP7 VLPs非常适合以高度免疫原性的形式展示多种肽。(C) 2010 Elsevier Ltd.版权所有。
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. (C) 2010 Elsevier Ltd. All rights reserved.