College of Veterinary Medicine, Jilin University, Changchun, 130062, Jilin, China; Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, 130122, Jilin, China.
Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, 130122, Jilin, China.
Antiviral Res. 2024 May;225:105854. doi: 10.1016/j.antiviral.2024.105854. Epub 2024 Mar 5.
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with frequent mutations has seriously damaged the effectiveness of the 2019 coronavirus disease (COVID-19) vaccine. There is an urgent need to develop a broad-spectrum vaccine while elucidating the underlying immune mechanisms. Here, we developed a SARS-CoV-2 virus-like particles (VLPs) vaccine based on the Canarypox-virus vector (ALVAC-VLPs) using CRISPR/Cas9. Immunization with ALVAC-VLPs showed the effectively induce SARS-CoV-2 specific T and B cell responses to resist the lethal challenge of mouse adaptive strains. Notably, ALVAC-VLPs conferred protection in golden hamsters against SARS-CoV-2 Wuhan-Hu-1 (wild-type, WT) and variants (Beta, Delta, Omicron BA.1, and BA.2), as evidenced by the prevention of weight loss, reduction in lung and turbinate tissue damage, and decreased viral load. Further investigation into the mechanism of immune response induced by ALVAC-VLPs revealed that toll-like receptor 4 (TLR4) mediates the recruitment of dendritic cells (DCs) to secondary lymphoid organs, thereby initiating follicle assisted T (Tfh) cell differentiation, the proliferation of germinal center (GC) B cells and plasma cell production. These findings demonstrate the immunogenicity and efficacy of the safe ALVAC-VLPs vaccine against SARS-CoV-2 and provide valuable insight into the development of COVID-19 vaccine strategies.
严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）变异株频繁突变的出现严重损害了 2019 冠状病毒病（COVID-19）疫苗的效力。迫切需要开发一种广谱疫苗，同时阐明其潜在的免疫机制。在这里，我们使用 CRISPR/Cas9 基于金丝雀痘病毒载体（ALVAC-VLPs）开发了一种 SARS-CoV-2 病毒样颗粒（VLPs）疫苗。ALVAC-VLPs 免疫可有效诱导 SARS-CoV-2 特异性 T 和 B 细胞反应，抵抗小鼠适应性株的致命挑战。值得注意的是，ALVAC-VLPs 可保护金黄地鼠免受 SARS-CoV-2 武汉株（野生型，WT）和变异株（Beta、Delta、Omicron BA.1 和 BA.2）的侵害，表现为体重减轻、肺和鼻甲组织损伤减少以及病毒载量降低。对 ALVAC-VLPs 诱导的免疫应答机制的进一步研究表明，Toll 样受体 4（TLR4）介导树突状细胞（DC）募集到次级淋巴器官，从而启动滤泡辅助性 T（Tfh）细胞分化、生发中心（GC）B 细胞增殖和浆细胞产生。这些发现证明了安全的 ALVAC-VLPs 疫苗对 SARS-CoV-2 的免疫原性和疗效，并为 COVID-19 疫苗策略的开发提供了有价值的见解。
