SARS-CoV-2亚单位疫苗制备及免疫原性初步研究  

Preliminary Study on Preparation and Immunogenicity of SARS-CoV-2Subunit Vaccine

作　　者：徐骁 黄涛 刘铁柱[1,2] 芜为 孙丽娜[1,2] 李川 李建东[1,2] 王世文[1,2] 王希良[3] XU Xiao;HUANG Tao;LIU Tiezhu;WU Wei;SUN Lina;LI Chuan;LI Jiandong;WANG Shiwen;WANG Xiliang(National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases(NITFID),National Institute for Viral Disease Control and Prevention,China CDC,Beijing 100052;NHC Key Laboratory of Medical Virology and Viral Diseases,National Institute for Viral Disease Control and Prevention,China CDC,Beijing 100052;State Key Laboratory of Pathogen and Biosecurity,Beijing Institute of Microbiology and Epidemiology,Academy of Military Medical Sciences(AMMS),Beijing 100071,China)

机构地区：[1]传染病溯源与智能决策全国重点实验室中国疾病预防控制中心病毒性疾病预防控制所,北京100052 [2]国家卫生健康委医学病毒学与病毒病重点实验室中国疾病预防控制中心病毒病预防控制所,北京100052 [3]病原与生物安全国家重点实验室,军事医学科学院北京微生物与流行病学研究所,北京100071

出　　处：《病毒学报》2024年第5期943-951,共9页Chinese Journal of Virology

摘　　要：严重急性呼吸系统综合征冠状病毒2(Severe acute respiratory symptom coronavirus 2,SARS-CoV-2)自2019年年末出现以来,给全人类造成了严重的公共卫生事件和社会经济负担。本实验以SARS-CoV-2突变株XBB1.5的受体结合域(Receptor binding domain,RBD)序列为疫苗核心分子串联SARS-CoV-2的全长S蛋白制备了亚单位纳米颗粒疫苗。将S蛋白的6个氨基酸残基突变为6个脯氨酸残基,提高表达量和蛋白质分子的稳定性。而且将弗林酶酶切位点进行突变以增加蛋白质的稳定性。在羧基端串联昆虫铁蛋白的氨基酸序列,利用铁蛋白纳米颗粒多面体可结合抗原蛋白的特性,增加抗原递呈。在氢氧化铝和CpG1018双佐剂组合免疫小鼠后,可诱导小鼠产生针对SARS-CoV-2多种变异株的中和抗体,且可诱导小鼠产生了较强的细胞免疫和体液免疫。本研究表明,XBB1.5突变株RBD区域串联S蛋白全长序列及昆虫铁蛋白制备的纳米颗粒疫苗可以有效预防SARS-CoV-2变体,是一个很好的候选疫苗分子。Since the widespread of SARS-CoV-2 in the world at the end of 2019,it has had a huge negative impact on human society.In this paper,we reported a tandem subunit nanoparticle vaccine based on the sequence of the receptor binding domain(RBD)of the SARS-CoV-2 mutant strain XBB1.5 as the core molecule of the vaccine and concatenating the full-length S protein of SARS-CoV-2.In order to improve the expression level and the stability of the protein molecule,mutations of six proline residues were added.Moreover,modification of the cleavage site of Flynase was added to increase stability.Then,the amino acid sequence of human ferritin was connected,and the characteristics of multiple antigen proteins were combined on the surface of ferritin nanoparticles to increase the stimulation of antigen epitopes and increase antigen presentation.After immunizing mice with the combination of aluminum hydroxide and CpG1018 double adjuvant,the mice were produced neutralizing antibodies against multiple variants of COVID-19,and triggered relatively strong cellular and humoral immunity.Overall,the data in this paper suggest that the XBB1.5 mutant RBD plus S protein full-length tandem ferritin nanoparticle vaccine is effective against the SARS-CoV-2 variant and may have the ability to prevent future Sarbecvirus variants.

关 键 词：新型冠状病毒 亚单位疫苗 受体结合域 血管紧张素转化酶2 

分 类 号：R373.1[医药卫生—病原生物学]