| 586 | 0 | 385 |
| 下载次数 | 被引频次 | 阅读次数 |
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。
Abstract：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.
[1] Guebre-Xabier M, Patel N, Tian JH, et al. NVXCoV2373 vaccine protects Cynomolgus macaque upper and lower airways against SARS-CoV-2 challenge[J].Vaccine, 2020, 38(50):7892-7896. DOI:10. 1016/j.vaccine. 2020. 10. 064.
[2] Khoury DS, Cromer D, Reynaldi A, et al. Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection[J]. Nat Med, 2021, 27:1205-1211. DOI:10. 1038/s41591-021-01377-8.
[3] Lang-Meli J, Luxenburger H, Wild K, et al. SARSCoV-2-specific T-cell epitope repertoire in convalescent and mRNA-vaccinated individuals[J]. Nat Microbiol,2022, 7(5):675-679. DOI:10. 1038/s41564-022-01106-y.
[4] Li H, Zhang Y, Li D, et al. Enhanced protective immunity against SARS-CoV-2 elicited by a VSV vector expressing a chimeric spike protein[J]. Signal Transduct Target Ther, 2021, 6:389. DOI:10. 1038/s41392-021-00797-9.
[5] He C, Yang J, He X, et al. A bivalent recombinant vaccine targeting the S1 protein induces neutralizing antibodies against both SARS-CoV-2 variants and wildtype of the virus[J]. MedComm(2020), 2021, 2(3):430-441. DOI:10. 1002/mco2. 72.
[6] He C, Yang J, Hong W, et al. A self-assembled trimeric protein vaccine induces protective immunity against Omicron variant[J]. Nat Commun, 2022, 13:5459. DOI:10. 1038/s41467-022-33209-9.
[7] He WT, Musharrafieh R, Song G, et al. Targeted isolation of diverse human protective broadly neutralizing antibodies against SARS-like viruses[J]. Nat Immunol,2022, 23(6):960-970. DOI:10. 1038/s41590-022-01222-1.
[8] Li H, Zhao C, Zhang Y, et al. Establishment of replication-competent vesicular stomatitis virus-based recombinant viruses suitable for SARS-CoV-2 entry and neutralization assays[J]. Emerg Microbes Infect, 2020,9(1):2269-2277. DOI:10. 1080/22221751. 2020. 1830715.
[9] Zhang J, Hu Z, He J, et al. Safety and immunogenicity of a recombinant interferon-armed RBD dimer vaccine(V-01)for COVID-19 in healthy adults:a randomized,double-blind, placebo-controlled, phase I trial[J].Emerg Microbes Infect, 2021, 10(1):1589-1597.DOI:10. 1080/22221751. 2021. 1951126.
[10]Heitmann JS, Bilich T, Tandler C, et al. A COVID-19peptide vaccine for the induction of SARS-CoV-2 T cell immunity[J]. Nature, 2022, 601(7894):617-622.DOI:10. 1038/s41586-021-04232-5.
[11]Joyce MG, Chen WH, Sankhala RS, et al. SARSCoV-2 ferritin nanoparticle vaccines elicit broad SARS coronavirus immunogenicity[J]. Cell Rep, 2021, 37(12):110143. DOI:10. 1016/j. celrep. 2021. 110143.
[12]Jung MK, Shin EC. Phenotypes and functions of SARSCoV-2-reactive T cells[J]. Mol Cells, 2021, 44(6):401-407. DOI:10. 14348/molcells. 2021. 0079.
[13]Kang YF, Sun C, Zhuang Z, et al. Rapid development of SARS-CoV-2 spike protein receptor-binding domain self-assembled nanoparticle vaccine candidates[J]. ACS Nano, 2021, 15(2):2738-2752. DOI:10. 1021/acsnano. 0c08379.
[14]Liang JG, Su D, Song TZ, et al. S-Trimer, a COVID-19 subunit vaccine candidate, induces protective immunity in nonhuman Primates[J]. Nat Commun,2021, 12:1346. DOI:10. 1038/s41467-021-21634-1.
[15]Liebschner D, Afonine PV, Baker ML, et al.Macromolecular structure determination using X-rays,neutrons and electrons:recent developments in phenix[J]. Acta Crystallogr D Struct Biol, 2019, 75(pt 10):861-877. DOI:10. 1107/s2059798319011471.
[16]Liu J, Yu J, McMahan K, et al. CD8 T cells contribute to vaccine protection against SARS-CoV-2 in macaques[J]. Sci Immunol, 2022, 7(77):eabq7647. DOI:10. 1126/sciimmunol. abq7647.
[17] Lu Y, Shen F, He WQ, et al. HR121 targeting HR2domain in S2 subunit of spike protein can serve as a broad-spectrum SARS-CoV-2 inhibitor via intranasal administration[J]. Acta Pharm Sin B, 2023, 13(8):3339-3351. DOI:10. 1016/j. apsb. 2023. 05. 030.
基本信息:
DOI：10.13242/j.cnki.bingduxuebao.004590
中图分类号:R392
引用信息:
[1]徐骁,黄涛,刘铁柱等.SARS-CoV-2亚单位疫苗制备及免疫原性初步研究[J].病毒学报,2024,40(05):943-951.DOI:10.13242/j.cnki.bingduxuebao.004590.
基金信息: