Foot-and-mouth disease vaccine with insertion of a 24-amino acid VP1 G-H loop epitope of the Cathay virus provides broad antigenic coverage

IF 4.3 3区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Applied Microbiology and Biotechnology Pub Date : 2025-09-27 DOI:10.1007/s00253-025-13545-8

Keqiang Zhang, Jingjing Zha, Pu Sun, Yifan Ouyang, Xingze Zhang, Xueqing Ma, Feng Liu, Dong Li, Huifang Bao, Yimei Cao, Xingwen Bai, Yuanfang Fu, Kun Li, Hong Yuan, Jing Zhang, Zhixun Zhao, Jian Wang, Qiang Zhang, Zaixin Liu, Zengjun Lu, Pinghua Li

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引用次数: 0

Abstract

Vaccination with inactivated whole-virus vaccines remains the most effective measure for controlling foot-and-mouth disease virus (FMDV) transmission and disease outbreaks. However, the existing type O FMDV vaccines show suboptimal efficacy and antigenic mismatch to the circulating Cathay viruses in China, thus requiring the development of a new vaccine. The VP1 G-H loop is a hypervariable region and plays a pivotal role in the protective immunity induced by FMDV vaccines. Here, we engineered four recombinant FMDVs with insertions of a 20-amino acid (aa) or a 24-aa G-H loop epitope of a prevalent Cathay strain upstream or downstream of the RGD (Arg-Gly-Asp) motif. The recombinant viruses with insertions upstream of the RGD motif retained parental virus-like plaque morphology and replication kinetics and maintained genetic stability even after 20 serial passages. In contrast, the downstream insertion variants exhibited small plaque morphology, reduced growth capacity, and acquired 1 or 2 aa mutations in the capsid proteins by passage 20. The parental virus vaccine induced high titer protective mean neutralizing antibodies (> 1:128) against viruses of the Mya98, PanAsia, and Ind-2001 lineages but failed to elicit protective mean neutralizing antibodies (< 1:22) to the Cathay virus after 28 days vaccination (dpv) in pigs. In contrast, vaccines containing upstream insertions both exhibited protective immune response to viruses of four lineages. Especially, pigs vaccinated with vaccine containing a 24-aa insertion produced significantly higher mean neutralizing antibody against the Cathay virus (p < 0.01), compared to those vaccinated with vaccine having a 20-aa insertion, indicating that the recombinant virus with 24-aa insertion has great potential as a vaccine candidate for serotype O FMD control. This study provides crucial insights for designing FMDV vaccines in the future.

• This study firstly reported that FMDV can tolerate a 24-aa insertion in the VP1 G-H loop

• The G-H loop insertions at different sites of FMDV VP1 have different impacts on viral replication capacity

• Vaccines containing the G-H loop insertions can induce markedly high neutralizing antibodies to the Cathay virus

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插入24个氨基酸的国泰病毒VP1 G-H环表位的口蹄疫疫苗提供了广泛的抗原覆盖

接种灭活全病毒疫苗仍然是控制口蹄疫病毒传播和疾病暴发的最有效措施。然而，现有的O型FMDV疫苗对中国流行的国泰病毒表现出不理想的疗效和抗原不匹配，因此需要开发新的疫苗。VP1 G-H环是一个高变区，在FMDV疫苗诱导的保护性免疫中起关键作用。在这里，我们设计了四个重组fmdv，在RGD （arg - gy - asp）基序的上游或下游插入一个20个氨基酸（aa）或24个氨基酸的国泰菌株G-H环表位。在RGD基序上游插入的重组病毒即使在连续20次传代后仍能保持亲本病毒样斑块形态和复制动力学，并保持遗传稳定性。相比之下，下游插入变异表现出较小的斑块形态，生长能力降低，并且在衣壳蛋白中获得1或2个aa突变。亲本病毒疫苗诱导了针对Mya98、PanAsia和Ind-2001病毒谱系的高滴度保护性平均中和抗体（< 1:128），但在接种28天后（dpv），未能诱导出针对国泰病毒的保护性平均中和抗体（< 1:22）。相比之下，含有上游插入的疫苗对四种谱系的病毒都表现出保护性免疫反应。特别是，与接种含有24-aa插入的疫苗的猪相比，接种含有24-aa插入的疫苗的猪对国泰病毒产生的平均中和抗体显著高于接种含有20-aa插入的疫苗的猪（p < 0.01），这表明含有24-aa插入的重组病毒作为血清O型口蹄疫控制的候选疫苗具有很大的潜力。这项研究为未来设计FMDV疫苗提供了重要的见解。•本研究首次报道了FMDV可以耐受VP1 G-H环中24-aa的插入•G-H环在FMDV VP1不同位点的插入对病毒复制能力有不同的影响•含有G-H环插入的疫苗可以诱导国泰病毒的高中和抗体

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Applied Microbiology and Biotechnology 工程技术-生物工程与应用微生物

CiteScore

10.00

自引率

4.00%

发文量

535

审稿时长

2 months

期刊介绍： Applied Microbiology and Biotechnology focusses on prokaryotic or eukaryotic cells, relevant enzymes and proteins; applied genetics and molecular biotechnology; genomics and proteomics; applied microbial and cell physiology; environmental biotechnology; process and products and more. The journal welcomes full-length papers and mini-reviews of new and emerging products, processes and technologies.