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拉沙热腺病毒载体疫苗候选物的构建与免疫评价。

Construction and Immunological Evaluation of an Adenoviral Vector-Based Vaccine Candidate for Lassa Fever.

机构信息

Laboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing 100071, China.

出版信息

Viruses. 2021 Mar 15;13(3):484. doi: 10.3390/v13030484.

Abstract

Lassa virus (LASV) is a rodent-borne arenavirus circulating in West African regions that causes Lassa fever (LF). LF is normally asymptomatic at the initial infection stage, but can progress to severe disease with multiorgan collapse and hemorrhagic fever. To date, the therapeutic choices are limited, and there is no approved vaccine for avoiding LASV infection. Adenoviral vector-based vaccines represent an effective countermeasure against LASV because of their safety and adequate immunogenicity, as demonstrated in use against other emerging viral infections. Here, we constructed and characterized a novel Ad5 (E1-, E3-) vectored vaccine containing the glycoprotein precursor (GPC) of LASV. Ad5-GPC elicited both humoral and cellular immune responses in BALB/c mice. Moreover, a bioluminescent imaging-based BALB/c mouse model infected with GPC-bearing and luciferase-expressing replication-incompetent LASV pseudovirus was utilized to evaluate the vaccine efficacy. The bioluminescence intensity of immunized mice was significantly lower than that of control mice after being inoculated with LASV pseudovirus. This study suggests that Ad5-GPC represents a potential vaccine candidate against LF.

摘要

拉萨病毒(LASV)是一种在西非地区传播的啮齿动物携带的沙粒病毒,可引起拉萨热(LF)。LF 在初次感染时通常无症状,但可进展为多器官衰竭和出血热等严重疾病。迄今为止,治疗选择有限,并且没有针对 LASV 感染的批准疫苗。腺病毒载体疫苗因其安全性和足够的免疫原性而成为针对 LASV 的有效对策,这在针对其他新发病毒感染的应用中得到了证明。在这里,我们构建并表征了一种新型的含有 LASV 糖蛋白前体(GPC)的 Ad5(E1-、E3-)载体疫苗。Ad5-GPC 在 BALB/c 小鼠中引发了体液和细胞免疫反应。此外,利用携带 GPC 和表达荧光素酶的复制缺陷型 LASV 假病毒感染的基于生物发光成像的 BALB/c 小鼠模型来评估疫苗的功效。接种 LASV 假病毒后,免疫小鼠的生物发光强度明显低于对照小鼠。这项研究表明,Ad5-GPC 是一种针对 LF 的潜在疫苗候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7de4/8001012/17fd37a2544a/viruses-13-00484-g001.jpg

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