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经口免疫缺失非结构蛋白 1 的减毒活流感病毒可诱导小鼠产生广泛的保护性免疫。

Sublingual immunization with a live attenuated influenza a virus lacking the nonstructural protein 1 induces broad protective immunity in mice.

机构信息

International Vaccine Institute, Seoul, Korea.

出版信息

PLoS One. 2012;7(6):e39921. doi: 10.1371/journal.pone.0039921. Epub 2012 Jun 27.

DOI:10.1371/journal.pone.0039921
PMID:22761928
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3384633/
Abstract

The nonstructural protein 1 (NS1) of influenza A virus (IAV) enables the virus to disarm the host cell type 1 IFN defense system. Mutation or deletion of the NS1 gene leads to attenuation of the virus and enhances host antiviral response making such live-attenuated influenza viruses attractive vaccine candidates. Sublingual (SL) immunization with live influenza virus has been found to be safe and effective for inducing protective immune responses in mucosal and systemic compartments. Here we demonstrate that SL immunization with NS1 deleted IAV (DeltaNS1 H1N1 or DeltaNS1 H5N1) induced protection against challenge with homologous as well as heterosubtypic influenza viruses. Protection was comparable with that induced by intranasal (IN) immunization and was associated with high levels of virus-specific antibodies (Abs). SL immunization with DeltaNS1 virus induced broad Ab responses in mucosal and systemic compartments and stimulated immune cells in mucosa-associated and systemic lymphoid organs. Thus, SL immunization with DeltaNS1 offers a novel potential vaccination strategy for the control of influenza outbreaks including pandemics.

摘要

甲型流感病毒（IAV）的非结构蛋白 1（NS1）使病毒能够破坏宿主细胞的 I 型干扰素防御系统。NS1 基因的突变或缺失会导致病毒减毒，并增强宿主抗病毒反应，使这种减毒流感病毒成为有吸引力的疫苗候选物。已经发现，通过舌下（SL）接种活流感病毒可以安全有效地诱导黏膜和全身部位的保护性免疫反应。在这里，我们证明，用缺失 NS1 的甲型流感病毒（DeltaNS1 H1N1 或 DeltaNS1 H5N1）进行 SL 免疫接种可以预防同源和异源流感病毒的挑战。这种保护作用与鼻腔内（IN）免疫接种诱导的保护作用相当，并与高水平的病毒特异性抗体（Abs）有关。DeltaNS1 病毒的 SL 免疫接种在黏膜和全身部位诱导了广泛的 Ab 反应，并刺激了黏膜相关和全身淋巴器官中的免疫细胞。因此，DeltaNS1 的 SL 免疫接种为控制流感爆发（包括大流行）提供了一种新的潜在疫苗接种策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af1d/3384633/42b1975baace/pone.0039921.g008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af1d/3384633/5ea918418995/pone.0039921.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af1d/3384633/42b1975baace/pone.0039921.g008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af1d/3384633/42b1975baace/pone.0039921.g008.jpg

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