Three in one: An effective and universal vaccine expressing heterologous tandem RBD trimer by rabies virus vector protects mice against SARS-CoV-2

IF 4.5 2区 医学 Q1 PHARMACOLOGY & PHARMACY Antiviral research Pub Date : 2024-05-11 DOI:10.1016/j.antiviral.2024.105905
Jingbo Huang , Weiqi Wang , Hailun Li , Yujie Bai , Yumeng Song , Cuicui Jiao , Hongli Jin , Pei Huang , Haili Zhang , Xianzhu Xia , Feihu Yan , Yuanyuan Li , Hualei Wang
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Abstract

The rapid emergence of Severe Acute Respiratory Syndrome Coronavirus type 2 (SARS-CoV-2) variants, coupled with severe immune evasion and imprinting, has jeopardized the vaccine efficacy, necessitating urgent development of broad protective vaccines. Here, we propose a strategy employing recombinant rabies viruses (RABV) to create a universal SARS-CoV-2 vaccine expressing heterologous tandem receptor-binding domain (RBD) trimer from the SARS-CoV-2 Prototype, Delta, and Omicron strains (SRV-PDO). The results of mouse immunization indicated that SRV-PDO effectively induced cellular and humoral immune responses, and demonstrated higher immunogenicity and broader SARS-CoV-2 neutralization compared to the recombinant RABVs that only expressed RBD monomers. Moreover, SRV-PDO exhibited full protection against SARS-CoV-2 in the challenge assay. This study demonstrates that recombinant RABV expressing tandem RBD-heterotrimer as a multivalent immunogen could elicit a broad-spectrum immune response and potent protection against SARS-CoV-2, making it a promising candidate for future human or veterinary vaccines and offering a novel perspective in other vaccine design.

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三合一:通过狂犬病毒载体表达异源串联 RBD 三聚体的有效通用疫苗可保护小鼠免受 SARS-CoV-2 的感染。
严重急性呼吸系统综合征冠状病毒 2 型(SARS-CoV-2)变种的迅速出现,加上严重的免疫逃避和印迹,已危及疫苗的效力,因此迫切需要开发具有广泛保护作用的疫苗。在此,我们提出了一种采用重组狂犬病毒(RABV)的策略,从 SARS-CoV-2 原型、Delta 和 Omicron 株(SRV-PDO)中提取表达异源串联受体结合域(RBD)三聚体的通用 SARS-CoV-2 疫苗。小鼠免疫结果表明,与仅表达 RBD 单体的重组 RABV 相比,SRV-PDO 能有效诱导细胞和体液免疫反应,并表现出更高的免疫原性和更广泛的 SARS-CoV-2 中和作用。此外,SRV-PDO 在挑战试验中表现出对 SARS-CoV-2 的全面保护。这项研究表明,表达串联 RBD-三聚体作为多价免疫原的重组 RABV 可引起广谱免疫反应,并对 SARS-CoV-2 提供强效保护,使其成为未来人类或兽医疫苗的理想候选物,并为其他疫苗设计提供了新的视角。
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来源期刊
Antiviral research
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.
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