State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun 130062, China; Department of Chinese Medicine, The First Hospital of Jilin University, Changchun 130021, China.
Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130122, China.
Antiviral Res. 2024 Jul;227:105905. doi: 10.1016/j.antiviral.2024.105905. Epub 2024 May 11.
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.
严重急性呼吸综合征冠状病毒 2 型(SARS-CoV-2)变体的迅速出现,加上严重的免疫逃逸和印迹,危及了疫苗的疗效,因此需要紧急开发广泛保护的疫苗。在这里,我们提出了一种利用重组狂犬病病毒(RABV)的策略,创建一种通用的 SARS-CoV-2 疫苗,该疫苗表达来自 SARS-CoV-2 原型、Delta 和奥密克戎株的异源串联受体结合域(RBD)三聚体(SRV-PDO)。小鼠免疫的结果表明,SRV-PDO 能够有效诱导细胞和体液免疫反应,与仅表达 RBD 单体的重组 RABV 相比,具有更高的免疫原性和更广泛的 SARS-CoV-2 中和作用。此外,SRV-PDO 在攻毒试验中对 SARS-CoV-2 具有完全保护作用。本研究表明,表达串联 RBD-异源三聚体的重组 RABV 作为多价免疫原,可以引发广谱免疫反应和对 SARS-CoV-2 的有效保护,使其成为未来人类或兽医疫苗的有前途的候选物,并为其他疫苗设计提供了新的视角。
Emerg Microbes Infect. 2024-12
Front Vet Sci. 2024-9-25