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基于牛白血病病毒相关肽的 Qβ 缀合物的设计与合成,可在小鼠中诱导产生长效中和抗体。

Design and Synthesis of Bovine Leukemia Virus-Associated Peptide-Based Qβ Conjugate Eliciting Long-Lasting Neutralizing Antibodies in Mice.

机构信息

Department of Chemistry, Michigan State University, East Lansing, Michigan 48824, United States.

Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, Michigan 48824, United States.

出版信息

ACS Infect Dis. 2022 May 13;8(5):1031-1040. doi: 10.1021/acsinfecdis.2c00001. Epub 2022 Apr 28.

DOI:10.1021/acsinfecdis.2c00001
PMID:35482583
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9112674/
Abstract

Bovine leukemia virus (BLV) is a C-type retrovirus of cattle that causes huge economic losses with high infection rates in the majority of countries worldwide. To develop an anti-BLV vaccine, we constructed a peptide conjugate using the envelope glycoprotein gp51-peptide epitope, a putative receptor-binding site. This highly antigenic peptide was covalently linked to a mutant bacteriophage carrier (mQβ) using two different linker strategies, isothiocyanate (NCS) and dinitrophenyl adipate. Both constructs elicited higher anti-BLV peptide IgG titers than the corresponding conjugate with keyhole limpet hemocyanin protein carrier (gold standard) in mice with the NCS linker strategy requiring less sample processing. The mQβ-gp51-peptide construct is the first BLV peptide-based vaccine candidate to generate durable immunity (>539 days), which recognized both native gp51 protein and BLV particles and significantly decreased fusion of a susceptible cell line exposed to infectious BLV. These results support the high translational and animal health potential of the vaccine construct.

摘要

牛白血病病毒(BLV)是一种牛的 C 型逆转录病毒,在世界上大多数国家,其感染率很高,给畜牧业带来了巨大的经济损失。为了开发抗 BLV 疫苗,我们使用包膜糖蛋白 gp51 肽表位(假定的受体结合位点)构建了一种肽缀合物。该高度抗原性的肽通过两种不同的连接子策略(异硫氰酸酯(NCS)和二硝基苯戊二酸)与突变噬菌体载体(mQβ)共价连接。与相应的与钥孔血蓝蛋白载体(金标准)的缀合物相比,两种构建体在 NCS 连接子策略下,在小鼠中引发了更高的抗 BLV 肽 IgG 滴度,所需的样品处理更少。mQβ-gp51-peptide 构建体是第一个基于 BLV 肽的疫苗候选物,可产生持久的免疫力(>539 天),可识别天然 gp51 蛋白和 BLV 颗粒,并显著降低了易感染 BLV 的细胞系暴露于传染性 BLV 时的融合。这些结果支持该疫苗构建体的高转化和动物健康潜力。

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ACS Infect Dis. 2022 May 13;8(5):1031-1040. doi: 10.1021/acsinfecdis.2c00001. Epub 2022 Apr 28.
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ACS Chem Biol. 2022 Nov 18;17(11):3047-3058. doi: 10.1021/acschembio.1c00906. Epub 2022 Feb 10.
2
Chemoenzymatic Synthesis of 9NHAc-GD2 Antigen to Overcome the Hydrolytic Instability of O-Acetylated-GD2 for Anticancer Conjugate Vaccine Development.酶促合成 9NHAc-GD2 抗原以克服 O-乙酰化-GD2 的水解不稳定性,用于抗癌偶联疫苗的开发。
Angew Chem Int Ed Engl. 2021 Nov 2;60(45):24179-24188. doi: 10.1002/anie.202108610. Epub 2021 Oct 4.
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Highly accurate protein structure prediction with AlphaFold.利用 AlphaFold 进行高精度蛋白质结构预测。
Nature. 2021 Aug;596(7873):583-589. doi: 10.1038/s41586-021-03819-2. Epub 2021 Jul 15.
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Microb Pathog. 2020 Dec;149:104417. doi: 10.1016/j.micpath.2020.104417. Epub 2020 Jul 27.
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BLV: lessons on vaccine development.BLV:疫苗研发的经验教训。
Retrovirology. 2019 Oct 7;16(1):26. doi: 10.1186/s12977-019-0488-8.
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