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一种利用卡介苗免疫既往史的病毒疫苗设计可预防埃博拉病毒。

A viral vaccine design harnessing prior BCG immunization confers protection against Ebola virus.

机构信息

Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, United States.

Laboratory of Virology, Rocky Mountain Laboratories, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institute of Health, Hamilton, MT, United States.

出版信息

Front Immunol. 2024 Jul 16;15:1429909. doi: 10.3389/fimmu.2024.1429909. eCollection 2024.

DOI:10.3389/fimmu.2024.1429909
PMID:39081315
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11286471/
Abstract

Previous studies have demonstrated the efficacy and feasibility of an anti-viral vaccine strategy that takes advantage of pre-existing CD4 helper T (Th) cells induced by bacille Calmette-Guérin (BCG) vaccination. This strategy uses immunization with recombinant fusion proteins comprised of a cell surface expressed viral antigen, such as a viral envelope glycoprotein, engineered to contain well-defined BCG Th cell epitopes, thus rapidly recruiting Th cells induced by prior BCG vaccination to provide intrastructural help to virus-specific B cells. In the current study, we show that Th cells induced by BCG were localized predominantly outside of germinal centers and promoted antibody class switching to isotypes characterized by strong Fc receptor interactions and effector functions. Furthermore, BCG vaccination also upregulated FcγR expression to potentially maximize antibody-dependent effector activities. Using a mouse model of Ebola virus (EBOV) infection, this vaccine strategy provided sustained antibody levels with strong IgG2c bias and protection against lethal challenge. This general approach can be easily adapted to other viruses, and may be a rapid and effective method of immunization against emerging pandemics in populations that routinely receive BCG vaccination.

摘要

先前的研究已经证明了一种利用卡介苗（BCG）接种诱导的固有 CD4 辅助性 T（Th）细胞的抗病毒疫苗策略的有效性和可行性。该策略利用免疫接种重组融合蛋白，该融合蛋白由细胞表面表达的病毒抗原组成，如病毒包膜糖蛋白，经工程设计包含明确的 BCG Th 细胞表位，从而迅速招募由先前 BCG 接种诱导的 Th 细胞，为病毒特异性 B 细胞提供结构内帮助。在本研究中，我们表明，BCG 诱导的 Th 细胞主要定位于生发中心之外，并促进抗体类别转换为具有强 Fc 受体相互作用和效应功能的同种型。此外，BCG 接种还上调了 FcγR 的表达，以最大限度地提高抗体依赖性效应功能。使用埃博拉病毒（EBOV）感染的小鼠模型，该疫苗策略提供了持续的抗体水平，具有强烈的 IgG2c 偏向性，并能抵御致命性挑战。这种通用方法可以很容易地适应其他病毒，并且可能是针对常规接受 BCG 接种的人群中出现的大流行迅速而有效的免疫接种方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b937/11286471/8ab6b118ac0b/fimmu-15-1429909-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b937/11286471/124cb64944e2/fimmu-15-1429909-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b937/11286471/bce0d409a768/fimmu-15-1429909-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b937/11286471/0973164ee888/fimmu-15-1429909-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b937/11286471/8ab6b118ac0b/fimmu-15-1429909-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b937/11286471/124cb64944e2/fimmu-15-1429909-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b937/11286471/793939e4a87e/fimmu-15-1429909-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b937/11286471/bce0d409a768/fimmu-15-1429909-g005.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b937/11286471/8ab6b118ac0b/fimmu-15-1429909-g007.jpg

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