Development of nanoparticle vaccines utilizing designed Fc-binding homo-oligomers and RBD-Fc of SARS-CoV-2

IF 4.5 2区医学 Q1 PHARMACOLOGY & PHARMACY

Antiviral research Pub Date : 2024-05-21 DOI:10.1016/j.antiviral.2024.105917

Yucai Liang , Weiling Xiao , Yuan Peng , Shengshuo Zhang , Jinhua Dong , Jun Zhao , Yuhui Wang , Mengtao Zhang , Zhijun Liu , Bowen Yu

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引用次数: 0

Abstract

The Fc-fused receptor binding domain (RBD-Fc) vaccine for SARS-CoV-2 has garnered significant attention for its capacity to provide effective and specific immune protection. However, its immunogenicity is limited, highlighting the need for improvement in clinical application. Nanoparticle delivery has been shown to be an effective method for enhancing antigen immunogenicity. In this study, we developed bivalent nanoparticle recombinant protein vaccines by assembling the RBD-Fc of SARS-CoV-2 and Fc-binding homo-oligomers o42.1 and i52.3 into octahedral and icosahedral nanoparticles. The formation of RBD-Fc nanoparticles was confirmed through structural characterization and cell binding experiments. Compared to RBD-Fc dimers, the nanoparticle vaccines induced more potent neutralizing antibodies (nAb) and stronger cellular immune responses. Therefore, using bivalent nanoparticle vaccines based on RBD-Fc presents a promising vaccination strategy against SARS-CoV-2 and offers a universal approach for enhancing the immunogenicity of Fc fusion protein vaccines.

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利用设计的 SARS-CoV-2 Fc 结合同源异构体和 RBD-Fc 开发纳米颗粒疫苗。

针对 SARS-CoV-2 的 Fc 融合受体结合域（RBD-Fc）疫苗因其提供有效和特异性免疫保护的能力而备受关注。然而，其免疫原性有限，在临床应用中亟待改进。纳米颗粒递送已被证明是提高抗原免疫原性的有效方法。在这项研究中，我们将 SARS-CoV-2 的 RBD-Fc 和 Fc 结合同源异构体 o42.1 和 i52.3 组装成八面体和二十面体纳米颗粒，开发了双价纳米颗粒重组蛋白疫苗。RBD-Fc 纳米粒子的形成通过结构表征和细胞结合实验得到了证实。与 RBD-Fc 二聚体相比，纳米颗粒疫苗能诱导更强的中和抗体（nAb）和更强的细胞免疫反应。因此，使用基于 RBD-Fc 的二价纳米颗粒疫苗是一种很有前景的 SARS-CoV-2 疫苗接种策略，并为增强 Fc 融合蛋白疫苗的免疫原性提供了一种通用方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Antiviral research 医学-病毒学

CiteScore

17.10

自引率

3.90%

发文量

157

审稿时长

34 days

期刊介绍： Antiviral Research is a journal that focuses on various aspects of controlling viral infections in both humans and animals. It is a platform for publishing research reports, short communications, review articles, and commentaries. The journal covers a wide range of topics including antiviral drugs, antibodies, and host-response modifiers. These topics encompass their synthesis, in vitro and in vivo testing, as well as mechanisms of action. Additionally, the journal also publishes studies on the development of new or improved vaccines against viral infections in humans. It delves into assessing the safety of drugs and vaccines, tracking the evolution of drug or vaccine-resistant viruses, and developing effective countermeasures. Another area of interest includes the identification and validation of new drug targets. The journal further explores laboratory animal models of viral diseases, investigates the pathogenesis of viral diseases, and examines the mechanisms by which viruses avoid host immune responses.