在SARS-CoV-2上病毒编码子优化Spike在开发COVID-19mRNA疫苗时增强免疫力
Chih-Jen Lai1,2, Dokyun Kim1,2, Seokmin Kang1,2
1Department of Cancer Biology and Infection Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Journal of medical virology
|October 20, 2023
概括
科学家们适应了一种持久病毒策略,以增强SARS-CoV-2mRNA疫苗. 通过优化编码子的使用,新的Spike mRNA疫苗增加了抗原表达,免疫反应和对致命病毒感染的保护.
科学领域:
- 病毒学 病毒学
- 疫苗开发 疫苗开发
- 分子生物学分子生物学
背景情况:
- 持久性疹病毒利用"跨诱导体"来优化异常病毒葡萄糖蛋白的表达.
- 优化codon的使用是提高病毒基因表达的关键策略.
研究的目的:
- 在SARS-CoV-2 Spike mRNA疫苗平台上应用"持久病毒编码子-使用-转导诱导"原则.
- 为了增强抗原表达,免疫反应,以及对SARS-CoV-2感染的保护.
主要方法:
- SARS-CoV-2尖端mRNA的Codon使用被修改为与疹简单病毒-1 (HSV-1) 糖蛋白B (gB) 相匹配.
- 在HSV-1的跨诱导体ICP27与代优化的Spike mRNA共同表达.
- 通过测量抗原表达,抗体标位,T细胞反应和对致命的SARS-CoV-2挑战的保护来评估疫苗的疗效.
主要成果:
- 在HSVgB-ICP27-codon优化的Spike mRNA疫苗显示显著增加了抗原表达和稳定性.
- 观察到显著高水平的总IgG,中和抗体和T细胞反应.
- 实现了对致命的SARS-CoV-2挑战的增强保护.
- 一种代码子优化的Delta变异Spike mRNA疫苗也显示出增强的抗原表达和长期保护.
结论:
- 一种新型的持续性病毒码子-使用-转导诱导mRNA疫苗平台增强了抗原表达并促进了长期的保护.
- 这一战略为开发更有效的mRNA疫苗来预防病毒感染提供了一个有希望的方法.
- 这些发现对未来针对SARS-CoV-2和其他病毒的疫苗设计有影响.
相关概念视频
02:28Leaky Scanning
5.1K
During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA. Marilyn Kozak discovered that the sequence RCCAUGG (where R...
5.1K
02:50Conjugated Proteins
18.3K
Simple proteins and protein complexes contain only amino acids. In contrast, many other proteins, called conjugated proteins, covalently bond with non-protein moieties.
Nucleoproteins are protein complexes that contain nucleic acids, categorized as deoxyribonucleoproteins (DNPs) or ribonucleoproteins (RNPs) respectively. The nucleosome is a typical example of a DNP where nuclear DNA is associated with histone proteins. The major antigen for the Covid-19 virus SARS-CoV is an RNP that is critical...
Nucleoproteins are protein complexes that contain nucleic acids, categorized as deoxyribonucleoproteins (DNPs) or ribonucleoproteins (RNPs) respectively. The nucleosome is a typical example of a DNP where nuclear DNA is associated with histone proteins. The major antigen for the Covid-19 virus SARS-CoV is an RNP that is critical...
18.3K
01:29Immune Response Against Viral Pathogens
798
The immune system's response to viral infections is a complex and coordinated process involving natural killer (NK) cells, T cell-mediated responses, and antibody-mediated responses.
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
798
00:36Viral Mutations
32.4K
A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material...
32.4K
01:05Single Nucleotide Polymorphisms-SNPs
15.2K
A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
15.2K
02:33Initiation of Translation
33.9K
Initiating translation is complex because it involves multiple molecules. Initiator tRNA, ribosomal subunits, and eukaryotic initiation factors (eIFs) are all required to assemble on the initiation codon of mRNA. This process consists of several steps that are mediated by different eIFs.
First, the initiator tRNA must be selected from the pool of elongator tRNAs by eukaryotic initiation factor 2 (eIF2). The initiator tRNA (Met-tRNAi) has conserved sequence elements including modified bases at...
First, the initiator tRNA must be selected from the pool of elongator tRNAs by eukaryotic initiation factor 2 (eIF2). The initiator tRNA (Met-tRNAi) has conserved sequence elements including modified bases at...
33.9K