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植物表达的马传染性贫血病毒 5 型嵌合病毒样颗粒(VLPs)和病毒蛋白 2(VP2)疫苗在 IFNAR 小鼠中的保护性免疫。

Protective immunity of plant-produced African horse sickness virus serotype 5 chimaeric virus-like particles (VLPs) and viral protein 2 (VP2) vaccines in IFNAR mice.

机构信息

Council for Scientific and Industrial Research (CSIR) Next Generation Health, Pretoria, South Africa.

Onderstepoort Biological Products SOC Ltd, Onderstepoort, South Africa.

出版信息

Vaccine. 2022 Aug 19;40(35):5160-5169. doi: 10.1016/j.vaccine.2022.06.079. Epub 2022 Jul 25.

Abstract

Next generation vaccines have the capability to contribute to and revolutionise the veterinary vaccine industry. African horse sickness (AHS) is caused by an arbovirus infection and is characterised by respiratory distress and/or cardiovascular failure and is lethal to horses. Mandatory annual vaccination in endemic areas curtails disease occurrence and severity. However, development of a next generation AHSV vaccine, which is both safe and efficacious, has been an objective globally for years. In this study, both AHSV serotype 5 chimaeric virus-like particles (VLPs) and soluble viral protein 2 (VP2) were successfully produced in Nicotiana benthamiana ΔXT/FT plants, partially purified and validated by gel electrophoresis, transmission electron microscopy and liquid chromatography-mass spectrometry (LC-MS/MS) based peptide sequencing before vaccine formulation. IFNAR mice vaccinated with the adjuvanted VLPs or VP2 antigens in a 10 µg prime-boost regime resulted in high titres of antibodies confirmed by both serum neutralising tests (SNTs) and enzyme-linked immunosorbent assays (ELISA). Although previous studies reported high titres of antibodies in horses when vaccinated with plant-produced AHS homogenous VLPs, this is the first study demonstrating the protective efficacy of both AHSV serotype 5 chimaeric VLPs and soluble AHSV-5 VP2 as vaccine candidates. Complementary to this, coating ELISA plates with the soluble VP2 has the potential to underpin serotype-specific serological assays.

摘要

下一代疫苗有能力为兽医疫苗行业做出贡献并带来革命。非洲马瘟(AHS)由虫媒病毒感染引起,其特征是呼吸窘迫和/或心血管衰竭,对马是致命的。在流行地区强制进行年度接种可以减少疾病的发生和严重程度。然而,多年来,开发一种既安全又有效的新一代 AHSV 疫苗一直是全球的目标。在这项研究中,AHSV 血清型 5 嵌合病毒样颗粒(VLPs)和可溶性病毒蛋白 2(VP2)都在 Nicotiana benthamiana ΔXT/FT 植物中成功生产,经过凝胶电泳、透射电子显微镜和基于液相色谱-质谱联用(LC-MS/MS)的肽测序进行部分纯化和验证,然后进行疫苗配方。用佐剂 VLPs 或 VP2 抗原对 IFNAR 小鼠进行 10µg 初免-加强免疫接种,可产生高滴度的抗体,这通过血清中和试验(SNTs)和酶联免疫吸附试验(ELISA)都得到了证实。尽管以前的研究报告称,用植物生产的 AHS 同源 VLPs 接种马时会产生高滴度的抗体,但这是首次证明 AHSV 血清型 5 嵌合 VLPs 和可溶性 AHSV-5 VP2 作为疫苗候选物具有保护效力的研究。作为补充,用可溶性 VP2 包被酶联免疫吸附试验板有可能为血清型特异性血清学检测提供基础。

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