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含保守神经氨酸酶或 M2 胞外结构域表位嵌合血凝素缀合物的灭活重组流感病毒的交叉保护作用。

Cross protection by inactivated recombinant influenza viruses containing chimeric hemagglutinin conjugates with a conserved neuraminidase or M2 ectodomain epitope.

机构信息

Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA.

Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA; Animal and Plant Quarantine Agency, Gimcheon, 39660, Republic of Korea.

出版信息

Virology. 2020 Nov;550:51-60. doi: 10.1016/j.virol.2020.08.003. Epub 2020 Aug 22.

DOI:10.1016/j.virol.2020.08.003
PMID:32882637
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7554235/
Abstract

Influenza virus neuraminidase (NA) contains a universally conserved epitope (NAe, NA). However, no studies have reported vaccines targeting this NA conserved epitope and inducing antibodies recognizing NAe. The extracellular domain of M2 (M2e) is considered as an attractive target for a universal influenza vaccine. We generated recombinant influenza H1N1 viruses expressing conserved epitopes in hemagglutinin (HA) molecules: NAe (NAe-HA) or M2e (M2e-HA) within the HA head domain. Inactivated recombinant NAe-HA and M2e-HA viruses were more effective in inducing IgG antibodies specific for an inserted conserved epitope than live recombinant virus. Recombinant inactivated M2e-HA virus vaccination induced cross protection against H3N2 virus with less weight loss compared to NAe-HA and was more effective in inducing humoral and cellular M2e immune responses. This study provides insight into developing recombinant influenza virus vaccines compatible with current platforms to induce antibody responses to conserved poorly immunogenic epitopes.

摘要

流感病毒神经氨酸酶（NA）包含一个普遍保守的表位（NAe，NA）。然而，目前尚无研究报道针对该 NA 保守表位并诱导识别 NAe 的抗体的疫苗。M2 的细胞外结构域（M2e）被认为是通用流感疫苗的一个有吸引力的靶标。我们生成了表达血凝素（HA）分子中保守表位的重组流感 H1N1 病毒：HA 头部结构域中的 NAe（NAe-HA）或 M2e（M2e-HA）。与活重组病毒相比，灭活的重组 NAe-HA 和 M2e-HA 病毒更有效地诱导针对插入的保守表位的 IgG 抗体。与 NAe-HA 相比，重组灭活 M2e-HA 病毒接种诱导了针对 H3N2 病毒的交叉保护作用，体重减轻较少，并且更有效地诱导了体液和细胞 M2e 免疫反应。本研究为开发与当前平台兼容的重组流感病毒疫苗以诱导针对保守的免疫原性差的表位的抗体反应提供了新的思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dc9/7554235/0399b637d183/nihms-1626759-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dc9/7554235/36c47f27b9d9/nihms-1626759-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dc9/7554235/d622def54adb/nihms-1626759-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dc9/7554235/8ce4178b8106/nihms-1626759-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dc9/7554235/3de08d53f3b4/nihms-1626759-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dc9/7554235/7962b6585ad3/nihms-1626759-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dc9/7554235/0399b637d183/nihms-1626759-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dc9/7554235/36c47f27b9d9/nihms-1626759-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dc9/7554235/d622def54adb/nihms-1626759-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dc9/7554235/8ce4178b8106/nihms-1626759-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dc9/7554235/3de08d53f3b4/nihms-1626759-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dc9/7554235/7962b6585ad3/nihms-1626759-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dc9/7554235/0399b637d183/nihms-1626759-f0006.jpg

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