Refocusing the Immune Response to Selected Epitopes on a Zika Virus Protein Antigen by Nanopatterning.
Refocusing the Immune Response to Selected Epitopes on a Zika Virus Protein Antigen by Nanopatterning.
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DOI：
10.1002/adhm.202002140
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发表时间：
2021-08
影响因子：
10
通讯作者：
Kane RS
中科院分区：
文献类型：
--
作者：
Castro A;Carreño JM;Duehr J;Krammer F;Kane RS
寨卡病毒（ZIKV）感染与严重中枢神经系统疾病的发展有关，但对ZIKV疫苗的需求仍未得到满足。尽管引发靶向ZIKV包膜（E）蛋白的结构域III（DIII）作为抗原的抗体的疫苗设计是有吸引力的策略，但靶向E蛋白的中和性差或交叉反应性差的抗体可能导致疾病的抗体依赖性增强。因此，我们决定使用我们以前报道的纳米图案化技术，该技术将非典型氨基酸的位点特异性掺入与聚乙二醇（PEG）对蛋白质的位点特异性功能化相结合，以屏蔽DIII上的选定表位。我们设计并表征了两种不同的纳米图案化DIII变体，并证明了用PEG屏蔽表位完全抑制了体外表位特异性抗体的结合。此外，用多价纳米图案化的DIII抗原免疫导致抗体应答重新聚焦于蛋白质表面上暴露的表位并远离潜在的增强表位。这种将抗体应答重定向至DIII蛋白的靶向区域的能力对于设计有效且安全的ZIKV疫苗应该是有用的。纳米图案化用于用聚乙二醇（PEG）屏蔽寨卡病毒包膜蛋白的结构域III上的选定表位。用多价纳米图案化抗原免疫使抗体应答重新集中于蛋白质表面上暴露的表位。这种将抗体反应重定向到靶向区域的能力对于设计安全有效的寨卡病毒疫苗应该是有用的。
Infections with Zika virus (ZIKV) have been linked to the development of severe central nervous system disorders, but the need for a ZIKV vaccine remains unmet. Although the design of vaccines that elicit antibodies targeting domain III (DIII) of the ZIKV envelope (E) protein as an antigen is an attractive strategy, poorly neutralizing or cross-reactive antibodies that target the E protein may lead to antibody-dependent enhancement of disease. We therefore decided to use our previously reported nanopatterning technique, which combines the site-specific incorporation of non-canonical amino acids with site-specific functionalization of the protein with polyethylene glycol (PEG), to shield selected epitopes on DIII. We designed and characterized two different nanopatterned DIII variants and demonstrated that epitope shielding with PEG completely inhibits the binding of epitope-specific antibodies in vitro. Furthermore, immunization with multivalent nanopatterned DIII antigens resulted in the refocusing of the antibody response towards the exposed epitopes on the protein surface and away from potentially enhancing epitopes. This ability to redirect the antibody response towards targeted regions of the DIII protein should be useful for the design of effective and safe ZIKV vaccines. Nanopatterning was used to shield selected epitopes on domain III of the Zika virus envelope protein with polyethylene glycol (PEG). Immunization with multivalent nanopatterned antigens refocused the antibody response towards the exposed epitopes on the protein surface. This ability to redirect the antibody response towards targeted regions should be useful for the design of safe and effective Zika virus vaccines.
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DOI：
10.15585/mmwr.mm6612a4
发表时间：
2017-03-31
期刊：
MMWR. Morbidity and mortality weekly report
影响因子：
--
作者：
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影响因子：
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DOI：
10.1007/978-1-4939-2272-7_12
发表时间：
2015
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
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通讯作者：
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DOI：
10.1073/pnas.83.22.8604
发表时间：
1986-11-01
影响因子：
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影响因子：
5.5
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通讯作者：
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