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表达嵌合细胞因子的通用流感病毒样颗粒疫苗的潜力。

The potential of a universal influenza virus-like particle vaccine expressing a chimeric cytokine.

机构信息

Nerome Institute of Biological Resources, Nago, Japan

Nerome Institute of Biological Resources, Nago, Japan.

出版信息

Life Sci Alliance. 2022 Nov 7;6(1). doi: 10.26508/lsa.202201548. Print 2023 Jan.

DOI:10.26508/lsa.202201548
PMID:36344085
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9644419/
Abstract

The efficacy of the current influenza vaccines is frequently reduced because of antigenic drift, a trade-off of developing improved vaccines with broad cross-protective activity against influenza A viruses. In this study, we have successfully constructed a chimeric cytokine (CC) comprising the M2 protein, influenza A neuraminidase stalk, and interleukin-12. We produced virus-like particles (VLPs) containing CC and influenza hemagglutinin (HA) proteins using a baculovirus system in Eri silkworm pupae. The protective efficacy of the CCHA-VLP vaccine was evaluated in mice. The CCFkH5HA-VLP vaccine increased the survival rates of BALB/c mice, infected with a lethal dose of PRH1 and HKH5 viruses, to 80% and 100%, respectively. The results suggested that CCHA-VLP successfully induced potent cross-reactive protective immunity against infection with homologous and heterologous subtypes of the influenza A virus. This is the first study to design a CC-containing HA-VLP vaccine and validate its protective efficacy.

摘要

由于抗原漂移，当前流感疫苗的功效经常降低，这是在开发针对甲型流感病毒具有广泛交叉保护活性的改良疫苗时的一种权衡。在这项研究中，我们成功构建了一种嵌合细胞因子 (CC)，包含 M2 蛋白、流感 A 神经氨酸酶茎和白细胞介素-12。我们使用杆状病毒系统在野蚕蛹中生产含有 CC 和流感血凝素 (HA) 蛋白的病毒样颗粒 (VLP)。我们在小鼠中评估了 CCHA-VLP 疫苗的保护效力。CCFkH5HA-VLP 疫苗使感染致死剂量 PRH1 和 HKH5 病毒的 BALB/c 小鼠的存活率分别提高到 80%和 100%。结果表明，CCHA-VLP 成功诱导了针对同源和异源甲型流感病毒亚型感染的有效交叉反应性保护免疫。这是首例设计包含 CC 的 HA-VLP 疫苗并验证其保护效力的研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05c6/9644419/ee791c594c9c/LSA-2022-01548_Fig11.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05c6/9644419/ee791c594c9c/LSA-2022-01548_Fig11.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05c6/9644419/9cd342df4df8/LSA-2022-01548_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05c6/9644419/deae83356fa2/LSA-2022-01548_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05c6/9644419/03555aa2a9e9/LSA-2022-01548_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05c6/9644419/09875400f5b3/LSA-2022-01548_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05c6/9644419/65567e7f4b11/LSA-2022-01548_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05c6/9644419/75f2b6423b8f/LSA-2022-01548_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05c6/9644419/7949bc572b96/LSA-2022-01548_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05c6/9644419/b59393d577e2/LSA-2022-01548_Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05c6/9644419/1c5aaeccf618/LSA-2022-01548_Fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05c6/9644419/8953d15bb476/LSA-2022-01548_Fig10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05c6/9644419/ee791c594c9c/LSA-2022-01548_Fig11.jpg

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