Poxvirus Vectors Activate Human NK and MAIT Cells in a Type I Interferon, IL-18, and Monocyte-Dependent Manner.

IF 3.6 3区 医学 Q2 IMMUNOLOGY
Journal of Immunology Research Pub Date : 2025-07-12 eCollection Date: 2025-01-01 DOI:10.1155/jimr/1203141
Kombo F N'guessan, Zhanna Shubin, Kawthar Machmach, Johan K Sandberg, Julie A Ake, Sandhya Vasan, Michael A Eller, Dominic Paquin-Proulx
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引用次数: 0

Abstract

Recombinant poxviruses have been extensively studied as vaccine vectors, yet the specific mechanisms by which they engage the immune system remain incompletely understood. ALVAC is a poxviral vector that was a component of the HIV vaccine used in the Thai RV144 trial, showing modest efficacy in reducing HIV acquisition. Here, we show that in vitro ALVAC-HIV infection of peripheral blood mononuclear cells (PBMCs) activates natural killer (NK) and mucosal-associated invariant T (MAIT) cells. This activation was partially dependent on monocytes, cGAS sensing, and production of IL-18 and type I IFN. Furthermore, ALVAC-HIV-mediated activation of NK and MAIT cells contributed to the activation of B cells. Modified vaccinia Ankara (MVA), another poxviral vector used for prevention of smallpox and mpox, similarly activated NK and MAIT cells. Overall, this suggests a conserved mechanism by which NK and MAIT cells could contribute to the immunogenicity of poxviral vectors.

痘病毒载体以I型干扰素、IL-18和单核细胞依赖的方式激活人NK和MAIT细胞。
重组痘病毒作为疫苗载体已被广泛研究,但其作用于免疫系统的具体机制仍不完全清楚。ALVAC是一种痘病毒载体,是泰国RV144试验中使用的艾滋病毒疫苗的一个组成部分,在减少艾滋病毒获得方面显示出适度的功效。在这里,我们发现体外ALVAC-HIV感染的外周血单核细胞(PBMCs)激活了自然杀伤细胞(NK)和粘膜相关的不变性T细胞(MAIT)。这种激活部分依赖于单核细胞、cGAS感应以及IL-18和I型IFN的产生。此外,alvac - hiv介导的NK和MAIT细胞的激活有助于B细胞的激活。改良安卡拉牛痘(MVA)是另一种用于预防天花和m痘的痘病毒载体,同样可以激活NK细胞和MAIT细胞。总的来说,这表明NK和MAIT细胞可以促进痘病毒载体的免疫原性的保守机制。
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来源期刊
CiteScore
6.90
自引率
2.40%
发文量
423
审稿时长
15 weeks
期刊介绍: Journal of Immunology Research is a peer-reviewed, Open Access journal that provides a platform for scientists and clinicians working in different areas of immunology and therapy. The journal publishes research articles, review articles, as well as clinical studies related to classical immunology, molecular immunology, clinical immunology, cancer immunology, transplantation immunology, immune pathology, immunodeficiency, autoimmune diseases, immune disorders, and immunotherapy.
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