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先进纳米螯合技术生产的纳米佐剂在灭活严重急性呼吸综合征冠状病毒2疫苗配方中的应用:细胞因子和IgG反应的初步结果

Nanoadjuvants Produced by Advanced Nanochelating Technology in the Inactivated-Severe Acute Respiratory Syndrome Coronavirus-2 Vaccine Formulation: Preliminary Results on Cytokines and IgG Responses.

作者信息

Kalanaky Somayeh, Fakharzadeh Saideh, Karimi Pegah, Hafizi Maryam, Jamaati Hamidreza, Hassanzadeh Seyed Mehdi, Khorasani Akbar, Mahdavi Mehdi, Nazaran Mohammad Hassan

机构信息

Department of Research and Development, Sodour Ahrar Shargh Company, Tehran, Iran.

Chronic Respiratory Diseases Research Center, NRITLD, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

出版信息

Viral Immunol. 2023 Jul-Aug;36(6):409-423. doi: 10.1089/vim.2023.0001. Epub 2023 Jul 28.

Abstract

Despite the great success of vaccines in various infectious diseases, most current vaccines are not effective enough, and on the contrary, clinically approved alum adjuvants cannot induce sufficient immune responses, including a potent cellular immune response to confer protection. In this study, we used Nanochelating Technology to develop novel nanoadjuvants to boost the potency of the alum-adjuvanted inactivated severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccine. BALB/c mice were immunized twice over 2 weeks with different doses of adjuvanted-vaccine formulations and immune responses were assessed. The analysis results of IFN- and IL-17 cytokines demonstrated the effectiveness of the nanoadjuvants produced by the Nanochelating Technology in shifting the alum-based vaccine toward a stronger Th1 pattern. In addition, these nanoadjuvants improved IL-2 cytokine response, which shows the efficacy of these novel formulations in inducing specific T lymphocyte proliferation. Using these nanoadjuvants increased IL-10 cytokine secretion that may be representative of a better immunoregulatory impact and may also potentially prevent immunopathology responses. Moreover, specific IgG titer analysis revealed the potency of these nanoadjuvants in improving humoral immune responses. The enzyme-linked immunosorbent assay of receptor-binding domain (RBD)-specific IgG response showed that the developed novel formulations induced strong IgG responses against this protein. This study shows that the nanostructures produced by the Advanced Nanochelating Technology have potent adjuvant effects on alum-based SARS-CoV-2 vaccines to not only compensate for alum weakness in inducing the cellular immune responses by smart regulation of the immune system but also significantly improve the humoral and cellular immune responses simultaneously.

摘要

尽管疫苗在各种传染病防治中取得了巨大成功,但目前大多数疫苗的效果仍不够理想,相反,临床批准的明矾佐剂无法诱导足够的免疫反应,包括无法产生有效的细胞免疫反应来提供保护。在本研究中,我们利用纳米螯合技术开发新型纳米佐剂,以增强明矾佐剂灭活严重急性呼吸综合征冠状病毒2(SARS-CoV-2)疫苗的效力。用不同剂量的佐剂疫苗制剂对BALB/c小鼠进行了为期2周的两次免疫,并评估了免疫反应。IFN和IL-17细胞因子的分析结果表明,纳米螯合技术生产的纳米佐剂能使基于明矾的疫苗向更强的Th1模式转变。此外,这些纳米佐剂改善了IL-2细胞因子反应,表明这些新型制剂在诱导特异性T淋巴细胞增殖方面的功效。使用这些纳米佐剂增加了IL-10细胞因子的分泌,这可能代表了更好的免疫调节作用,也可能潜在地预防免疫病理反应。此外,特异性IgG滴度分析揭示了这些纳米佐剂在改善体液免疫反应方面的效力。受体结合域(RBD)特异性IgG反应的酶联免疫吸附测定表明,所开发的新型制剂诱导了针对该蛋白的强烈IgG反应。本研究表明,先进纳米螯合技术产生的纳米结构对基于明矾的SARS-CoV-2疫苗具有强大的佐剂作用,不仅通过智能调节免疫系统弥补明矾在诱导细胞免疫反应方面的不足,还能同时显著改善体液免疫和细胞免疫反应。

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