Responses of primary human nasal epithelial cells to COVID-19 vaccine candidate.

IF 2.3 4区 医学 Q3 ALLERGY Asian Pacific journal of allergy and immunology Pub Date : 2024-01-06 DOI:10.12932/AP-230523-1623
Phissinee Jakaew, Tuksin Jearanaiwitayakul, Panuwat Midoeng, Promsin Masrinoul, Panya Sunintaboon, Sukathida Ubol
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Abstract

Background: Upper respiratory tract is the primary target of SARS-CoV-2. Therefore, nasal immune responses act as the first line of defense against SARS-CoV-2 infection.

Objective: We aim to investigate the immune responses of human nasal epithelial cells (HNEpCs) upon stimulation with a COVID-19 vaccine candidate. This candidate named RBD-NPs is composed of SARS-CoV-2 receptor-binding domain (RBD) encapsulated within the N,N,N-trimethyl chitosan nanoparticles (TMC-NPs).

Methods: HNEpCs were stimulated with RBD-NPs, empty NPs, or soluble RBD at various concentrations. After 24 and 48 h of treatment, cells viability and delivery of the immunogens were assessed using XTT assay and flow cytometry. Levels of cytokines and chemokines in the supernatant were quantified with Bio-plex Human Cytokine Assay. Communication between RBD-NPs-stimulated HNEpCs and monocyte-derived dendritic cells (MoDCs) was assessed through differentiation of MoDCs into mature phenotype.

Results: RBD-NPs as high as 100 μg exerted no toxicity to HNEpCs and could effectively be delivered to HNEpCs. Treatment of HNEpCs with RBD-NPs strongly activated production of several pro-inflammatory cytokines, chemokines, Th1-related cytokines and the monocytes/macrophages growth factors. Interestingly, soluble mediators secreted from RBD-NPs treated HNEpCs significantly upregulated the expression of maturation markers (CD80, CD83, CD86 and HLA-DR) on the MoDCs.

Conclusion: This study demonstrated that our COVID-19 vaccine candidate drove HNEpCs into immunologically competent cells that not only exerted anti-viral innate immune responses but also potently induced MoDCs maturation.

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原代人鼻上皮细胞对 COVID-19 候选疫苗的反应。
背景:上呼吸道是 SARS-CoV-2 的主要目标。因此,鼻腔免疫反应是抵御 SARS-CoV-2 感染的第一道防线:我们旨在研究人鼻上皮细胞(HNEpCs)在 COVID-19 候选疫苗刺激下的免疫反应。方法:用不同浓度的 RBD-NPs、空 NPs 或可溶性 RBD 刺激 HNEpCs。处理 24 和 48 小时后,使用 XTT 检测法和流式细胞术评估细胞活力和免疫原的传递。上清液中细胞因子和趋化因子的水平用 Bio-plex 人类细胞因子测定法进行量化。RBD-NPs刺激的HNEpCs与单核细胞衍生树突状细胞(MoDCs)之间的交流通过MoDCs分化成成熟表型进行评估:结果:高达 100 μg 的 RBD-NPs 对 HNEpCs 无毒性,并能有效地传递给 HNEpCs。用 RBD-NPs 处理 HNEpCs 能强烈激活多种促炎细胞因子、趋化因子、Th1 相关细胞因子和单核/巨噬细胞生长因子的产生。有趣的是,经 RBD-NPs 处理的 HNEpCs 所分泌的可溶性介质能显著上调 MoDCs 上成熟标志物(CD80、CD83、CD86 和 HLA-DR)的表达:这项研究表明,我们的 COVID-19 候选疫苗能将 HNEpCs 促成具有免疫能力的细胞,这些细胞不仅能产生抗病毒的先天性免疫反应,还能有效诱导 MoDCs 成熟。
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来源期刊
CiteScore
12.80
自引率
0.00%
发文量
74
审稿时长
>12 weeks
期刊介绍: The Asian Pacific Journal of Allergy and Immunology (APJAI) is an online open access journal with the recent impact factor (2018) 1.747 APJAI published 4 times per annum (March, June, September, December). Four issues constitute one volume. APJAI publishes original research articles of basic science, clinical science and reviews on various aspects of allergy and immunology. This journal is an official journal of and published by the Allergy, Asthma and Immunology Association, Thailand. The scopes include mechanism, pathogenesis, host-pathogen interaction, host-environment interaction, allergic diseases, immune-mediated diseases, epidemiology, diagnosis, treatment and prevention, immunotherapy, and vaccine. All papers are published in English and are refereed to international standards.
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