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经典与下一代 SARS-CoV-2 疫苗平台:生物技术策略和基因组变异。

Classical and Next-Generation Vaccine Platforms to SARS-CoV-2: Biotechnological Strategies and Genomic Variants.

机构信息

Institute of Technology in Immunobiologicals, Bio-Manguinhos, Oswaldo Cruz Foundation, Fiocruz, Avenida Brasil, 4365, Manguinhos, Rio de Janeiro 21040-900, Brazil.

Microbiology Division, Faculty of Sciences, University of Burgos, 09001 Burgos, Spain.

出版信息

Int J Environ Res Public Health. 2022 Feb 18;19(4):2392. doi: 10.3390/ijerph19042392.

Abstract

Several coronaviruses (CoVs) have been identified as human pathogens, including the α-CoVs strains HCoV-229E and HCoV-NL63 and the β-CoVs strains HCoV-HKU1 and HCoV-OC43. SARS-CoV, MERS-CoV, and SARS-CoV-2 are also classified as β-coronavirus. New SARS-CoV-2 spike genomic variants are responsible for human-to-human and interspecies transmissibility, consequences of adaptations of strains from animals to humans. The receptor-binding domain (RBD) of SARS-CoV-2 binds to receptor ACE2 in humans and animal species with high affinity, suggesting there have been adaptive genomic variants. New genomic variants including the incorporation, replacement, or deletion of the amino acids at a variety of positions in the S protein have been documented and are associated with the emergence of new strains adapted to different hosts. Interactions between mutated residues and RBD have been demonstrated by structural modelling of variants including D614G, B.1.1.7, B1.351, P.1, P2; other genomic variants allow escape from antibodies generated by vaccines. Epidemiological and molecular tools are being used for real-time tracking of pathogen evolution and particularly new SARS-CoV-2 variants. COVID-19 vaccines obtained from classical and next-generation vaccine production platforms have entered clinicals trials. Biotechnology strategies of the first generation (attenuated and inactivated virus-CoronaVac, CoVaxin; BBIBP-CorV), second generation (replicating-incompetent vector vaccines-ChAdOx-1; Ad5-nCoV; Sputnik V; JNJ-78436735 vaccine-replicating-competent vector, protein subunits, virus-like particles-NVX-CoV2373 vaccine), and third generation (nucleic-acid vaccines-INO-4800 (DNA); mRNA-1273 and BNT 162b (RNA vaccines) have been used. Additionally, dendritic cells (LV-SMENP-DC) and artificial antigen-presenting (aAPC) cells modified with lentiviral vector have also been developed to inhibit viral activity. Recombinant vaccines against COVID-19 are continuously being applied, and new clinical trials have been tested by interchangeability studies of viral vaccines developed by classical and next-generation platforms.

摘要

已鉴定出几种冠状病毒(CoVs)可引起人类疾病,包括α-CoV 株 HCoV-229E 和 HCoV-NL63 以及β-CoV 株 HCoV-HKU1 和 HCoV-OC43。SARS-CoV、MERS-CoV 和 SARS-CoV-2 也被归类为β-冠状病毒。新型 SARS-CoV-2 刺突基因组变异株可导致人际传播和种间传播,这是病毒从动物适应到人类的结果。SARS-CoV-2 的受体结合域(RBD)与人 ACE2 以及多种动物物种以高亲和力结合,表明存在适应性基因组变异株。已记录到新型基因组变异株,包括 S 蛋白中多种位置的氨基酸插入、替换或缺失,这些变异株与适应不同宿主的新菌株的出现有关。通过对 D614G、B.1.1.7、B1.351、P.1、P2 等变体的结构建模,已经证明了突变残基与 RBD 之间的相互作用;其他基因组变异株可以逃避疫苗产生的抗体。正在使用流行病学和分子工具实时跟踪病原体进化,特别是新型 SARS-CoV-2 变异株。从经典和下一代疫苗生产平台获得的 COVID-19 疫苗已进入临床试验。第一代生物技术策略(减毒和灭活病毒-CoronaVac、CoVaxin;BBIBP-CorV)、第二代(复制缺陷型载体疫苗-ChAdOx-1;Ad5-nCoV;Sputnik V;JNJ-78436735 疫苗-复制型载体,蛋白亚单位,病毒样颗粒-NVX-CoV2373 疫苗)和第三代(核酸疫苗-INO-4800(DNA);mRNA-1273 和 BNT 162b(RNA 疫苗)已经被使用。此外,还开发了带有慢病毒载体的树突状细胞(LV-SMENP-DC)和人工抗原呈递(aAPC)细胞,以抑制病毒活性。针对 COVID-19 的重组疫苗正在不断应用,通过对经典和下一代平台开发的病毒疫苗进行互换性研究,新的临床试验已得到测试。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cec/8877900/1fe9ba86b671/ijerph-19-02392-g001.jpg

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