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黏膜接种重组腺病毒编码的核蛋白可提供针对流感病毒感染的有效保护。

Mucosal vaccination with recombinant adenovirus encoding nucleoprotein provides potent protection against influenza virus infection.

机构信息

Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, Korea.

出版信息

PLoS One. 2013 Sep 25;8(9):e75460. doi: 10.1371/journal.pone.0075460. eCollection 2013.

DOI:10.1371/journal.pone.0075460
PMID:24086536
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3783479/
Abstract

Influenza vaccines that target the highly variable surface glycoproteins hemagglutinin and neuraminidase cause inconvenience of having vaccination every year. For this reason, development of universal vaccines targeting conserved viral components is needed. In this study, we generated recombinant adenovirus (rAd) vaccine encoding nucleoprotein (NP) of A/PR/8/34 influenza virus, designated rAd/NP. BALB/c mice were immunized intranasally or sublingually with rAd/NP vaccine and subsequently challenged with lethal doses of heterologous as well as homologous influenza viruses. We found that intranasal immunization of rAd/NP elicited strong mucosal IgA responses as well as stronger CD8 T-cell responses toward immunodominant K(d)-restricted NP147-155 epitope than sublingual immunization. Importantly, only single intranasal but not sublingual immunization of rAd/NP provides potent protection against both homologous and heterologous influenza virus challenges. These results suggest that recombinant rAd/NP could be a universal vaccine candidate for mucosal administration against influenza virus.

摘要

流感疫苗针对高度变异的表面糖蛋白血凝素和神经氨酸酶，导致每年都需要接种疫苗，非常不便。因此，需要开发针对保守病毒成分的通用疫苗。在这项研究中，我们生成了编码 A/PR/8/34 流感病毒核蛋白（NP）的重组腺病毒（rAd）疫苗，命名为 rAd/NP。BALB/c 小鼠通过鼻腔内或舌下途径接种 rAd/NP 疫苗，并随后用致死剂量的异源和同源流感病毒进行攻击。我们发现，鼻腔内接种 rAd/NP 可诱导强烈的黏膜 IgA 反应，以及针对免疫优势 K(d)限制的 NP147-155 表位的更强的 CD8 T 细胞反应，优于舌下接种。重要的是，只有单次鼻腔内接种 rAd/NP 而不是舌下接种就可以提供针对同源和异源流感病毒攻击的有效保护。这些结果表明，重组 rAd/NP 可能成为针对流感病毒的黏膜给药的通用疫苗候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9aa5/3783479/79ca7c1f0d3e/pone.0075460.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9aa5/3783479/8e9a8b4844b2/pone.0075460.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9aa5/3783479/4c5de33ab8d7/pone.0075460.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9aa5/3783479/ebcf933ce758/pone.0075460.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9aa5/3783479/fbe715a714c9/pone.0075460.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9aa5/3783479/15a01ab439a5/pone.0075460.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9aa5/3783479/79ca7c1f0d3e/pone.0075460.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9aa5/3783479/8e9a8b4844b2/pone.0075460.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9aa5/3783479/4c5de33ab8d7/pone.0075460.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9aa5/3783479/ebcf933ce758/pone.0075460.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9aa5/3783479/fbe715a714c9/pone.0075460.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9aa5/3783479/15a01ab439a5/pone.0075460.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9aa5/3783479/79ca7c1f0d3e/pone.0075460.g006.jpg

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