腺病毒载体疫苗可预防克里米亚-刚果出血热疾病在致死性挑战模型中的发生。

Adenoviral vectored vaccination protects against Crimean-Congo Haemorrhagic Fever disease in a lethal challenge model.

机构信息

The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.

The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.

出版信息

EBioMedicine. 2023 Apr;90:104523. doi: 10.1016/j.ebiom.2023.104523. Epub 2023 Mar 17.

DOI:10.1016/j.ebiom.2023.104523

PMID:36933409

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10025009/

Abstract

BACKGROUND

The tick-borne bunyavirus, Crimean-Congo Haemorrhagic Fever virus (CCHFV), can cause severe febrile illness in humans and has a wide geographic range that continues to expand due to tick migration. Currently, there are no licensed vaccines against CCHFV for widespread usage.

METHODS

In this study, we describe the preclinical assessment of a chimpanzee adenoviral vectored vaccine (ChAdOx2 CCHF) which encodes the glycoprotein precursor (GPC) from CCHFV.

FINDINGS

We demonstrate here that vaccination with ChAdOx2 CCHF induces both a humoral and cellular immune response in mice and 100% protection in a lethal CCHF challenge model. Delivery of the adenoviral vaccine in a heterologous vaccine regimen with a Modified Vaccinia Ankara vaccine (MVA CCHF) induces the highest levels of CCHFV-specific cell-mediated and antibody responses in mice. Histopathological examination and viral load analysis of the tissues of ChAdOx2 CCHF immunised mice reveals an absence of both microscopic changes and viral antigen associated with CCHF infection, further demonstrating protection against disease.

INTERPRETATION

There is the continued need for an effective vaccine against CCHFV to protect humans from lethal haemorrhagic disease. Our findings support further development of the ChAd platform expressing the CCHFV GPC to seek an effective vaccine against CCHFV.

FUNDING

This research was supported by funding from the Biotechnology and Biological Sciences Research Council (UKRI-BBSRC) [BB/R019991/1 and BB/T008784/1].

摘要

背景

蜱传布尼亚病毒，即克里米亚-刚果出血热病毒（CCHFV），可引起人类严重的发热疾病，且由于蜱的迁移，其地理分布范围广泛且不断扩大。目前，尚无针对 CCHFV 的广泛使用的许可疫苗。

方法

在本研究中，我们描述了一种 chimpanzee 腺病毒载体疫苗（ChAdOx2 CCHF）的临床前评估，该疫苗编码来自 CCHFV 的糖蛋白前体（GPC）。

发现

我们在此证明，在小鼠中，ChAdOx2 CCHF 疫苗接种可诱导体液和细胞免疫应答，在致命的 CCHF 攻毒模型中可实现 100%的保护。在与 Modified Vaccinia Ankara 疫苗（MVA CCHF）的异源疫苗方案中递送腺病毒疫苗可在小鼠中诱导最高水平的 CCHFV 特异性细胞介导和抗体应答。对 ChAdOx2 CCHF 免疫的小鼠的组织进行组织病理学检查和病毒载量分析，揭示了与 CCHF 感染相关的微观变化和病毒抗原均不存在，进一步证明了对疾病的保护。