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

Design and Synthesis of Bovine Leukemia Virus-Associated Peptide-Based Qβ Conjugate Eliciting Long-Lasting Neutralizing Antibodies in Mice.
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DOI:
10.1021/acsinfecdis.2c00001
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发表时间:
2022-05-13
影响因子:
5.3
通讯作者:
Huang, Xuefei
Huang, Xuefei
中科院分区:
医学2区
文献类型:
--
作者:
Chugh, Shivangi;Swenson, Cheryl;Yuzbasiyan-Gurkan, Vilma;Huang, Xuefei

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牛白血病病毒(BLV)是一种牛c型逆转录病毒,在世界上大多数国家,随着感染率的上升,造成了巨大的经济损失。为了开发抗blv疫苗,我们利用包膜糖蛋白gp51肽表位(一个假定的受体结合位点)构建了肽偶联物。这种高抗原性肽通过两种不同的连接策略,异硫氰酸酯(NCS)和己二硝基苯酯(二硝基苯)与突变噬菌体载体(mQβ)共价连接。两种构建物均比相应的锁孔帽贝血青素蛋白载体(金标准)在ncs连接体策略下的小鼠中获得更高的抗blv肽IgG滴度,需要较少的样品处理。mq - β-gp51肽构建物是首个产生持久免疫(bbb539天)的基于BLV肽的候选疫苗,它能识别天然gp51蛋白和BLV颗粒,并显著降低暴露于感染性BLV的易感细胞系的融合。这些结果支持该疫苗结构具有很高的转化和动物健康潜力。
Bovine leukemia virus (BLV) is a C-type retrovirus of cattle that causes huge economic losses with the infection rate escalated 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.
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