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利用乙型肝炎病毒核心抗原选择和放置表位以提高新型猪流行性腹泻病毒疫苗的病毒中和能力。

Epitope selection and their placement for increased virus neutralization in a novel vaccination strategy for porcine epidemic diarrhea virus utilizing the Hepatitis B virus core antigen.

机构信息

Department of Biological Systems Engineering, Virginia Tech, 1230 Washington St SW, Blacksburg, VA 24061, USA.

Department of Biological Systems Engineering, Virginia Tech, 1230 Washington St SW, Blacksburg, VA 24061, USA.

出版信息

Vaccine. 2018 Jul 16;36(30):4507-4516. doi: 10.1016/j.vaccine.2018.06.015. Epub 2018 Jun 15.

Abstract

Porcine epidemic diarrhea virus (PEDV) is a member of the Alphacoronaviridae genus within the Coronaviridae family. It is the causative agent of porcine epidemic diarrhea, a disease that can have mortality rates as high as 100% in suckling piglets. PEDV causes severe economic loss, and has been in existence for decades. A panzootic starting in 2010 renewed interest in the development of a universal vaccine toward PEDV. This report details several design changes made to a Hepatitis B virus core antigen (HBcAg)-based recombinant vaccine strategy, and their effect in vivo. Initially, several multi-antigen vaccine candidates were able to elicit antibodies specific to three out of four B-cell epitopes inserted into the chimeric proteins. However, a lack of virus neutralization led to a redesign of the vaccines. The focus of the newly redesigned vaccines was to elicit a strong immune response to the YSNIGVCK amino acid motif from PEDV. Genetically modified new vaccine candidates were able to elicit a strong antibody (Ab) response to the YSNIGVCK epitope, which correlated with an increased ability to neutralize the CO strain of PEDV. Additionally, the location of the inserted PEDV epitopes within the vector protein was shown to affect the immune recognition toward the native HBcAg during vaccination.

摘要

猪流行性腹泻病毒(PEDV)是冠状病毒科冠状病毒属的成员。它是猪流行性腹泻的病原体,在仔猪中的死亡率高达 100%。PEDV 造成严重的经济损失,已经存在了几十年。自 2010 年开始的大流行重新引起了人们对开发针对 PEDV 的通用疫苗的兴趣。本报告详细介绍了乙型肝炎病毒核心抗原(HBcAg)为基础的重组疫苗策略的几项设计变更及其在体内的效果。最初,几种多抗原疫苗候选物能够诱导针对插入嵌合蛋白中的四个 B 细胞表位中的三个的抗体。然而,缺乏病毒中和导致疫苗重新设计。新设计的疫苗的重点是诱导针对 PEDV 的 YSNIGVCK 氨基酸基序的强烈免疫反应。遗传修饰的新型疫苗候选物能够诱导针对 YSNIGVCK 表位的强烈抗体(Ab)反应,这与增加中和 PEDV CO 株的能力相关。此外,插入载体蛋白中的插入 PEDV 表位的位置显示会影响接种疫苗期间对天然 HBcAg 的免疫识别。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cac0/7172244/3be83e330516/gr1_lrg.jpg

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