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鼻腔内给予病毒样颗粒疫苗可诱导针对 SARS-CoV-2 及关注变异株的中和抗体。

Intranasal administration of a virus like particles-based vaccine induces neutralizing antibodies against SARS-CoV-2 and variants of concern.

机构信息

Department of Rheumatology and Immunology, University Hospital, Bern, Switzerland.

Department of BioMedical Research, University of Bern, Bern, Switzerland.

出版信息

Allergy. 2022 Aug;77(8):2446-2458. doi: 10.1111/all.15311. Epub 2022 Apr 15.

Abstract

BACKGROUND

The highly contagious SARS-CoV-2 is mainly transmitted by respiratory droplets and aerosols. Consequently, people are required to wear masks and maintain a social distance to avoid spreading of the virus. Despite the success of the commercially available vaccines, the virus is still uncontained globally. Given the tropism of SARS-CoV-2, a mucosal immune reaction would help to reduce viral shedding and transmission locally. Only seven out of hundreds of ongoing clinical trials are testing the intranasal delivery of a vaccine against COVID-19.

METHODS

In the current study, we evaluated the immunogenicity of a traditional vaccine platform based on virus-like particles (VLPs) displaying RBD of SARS-CoV-2 for intranasal administration in a murine model. The candidate vaccine platform, CuMV -RBD, has been optimized to incorporate a universal T helper cell epitope derived from tetanus-toxin and is self-adjuvanted with TLR7/8 ligands.

RESULTS

CuMV -RBD vaccine elicited a strong systemic RBD- and spike-IgG and IgA antibodies of high avidity. Local immune response was assessed, and our results demonstrate a strong mucosal antibody and plasma cell production in lung tissue. Furthermore, the induced systemic antibodies could efficiently recognize and neutralize different variants of concern (VOCs).

CONCLUSION

Our data demonstrate that intranasal administration of CuMV -RBD induces a protective systemic and local specific antibody response against SARS-CoV-2 and its VOCs.

摘要

背景

高传染性的 SARS-CoV-2 主要通过呼吸道飞沫和气溶胶传播。因此,人们需要戴口罩并保持社交距离,以避免病毒传播。尽管市售疫苗取得了成功,但该病毒在全球范围内仍未得到控制。鉴于 SARS-CoV-2 的嗜性,黏膜免疫反应有助于减少病毒在局部的脱落和传播。在数百项正在进行的临床试验中,只有 7 项正在测试针对 COVID-19 的鼻内递送疫苗。

方法

在本研究中,我们评估了基于展示 SARS-CoV-2 RBD 的病毒样颗粒 (VLPs) 的传统疫苗平台用于 COVID-19 的鼻腔给药的免疫原性。候选疫苗平台 CuMV-RBD 经过优化,可纳入破伤风毒素的通用 T 辅助细胞表位,并与 TLR7/8 配体自佐剂化。

结果

CuMV-RBD 疫苗引发了强烈的全身性 RBD 和刺突 IgG 和 IgA 抗体,具有高亲和力。评估了局部免疫反应,我们的结果表明在肺组织中产生了强烈的黏膜抗体和浆细胞。此外,诱导的系统抗体可以有效地识别和中和不同的关注变体 (VOCs)。

结论

我们的数据表明,CuMV-RBD 的鼻腔给药可诱导针对 SARS-CoV-2 及其 VOCs 的保护性全身和局部特异性抗体反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d996/9111403/4f12d1507e72/ALL-9999-0-g001.jpg

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