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扩展特异性T细胞到SARS-CoV-2的低突变区域使用mRNA电孔抗原呈现细胞

Elizabeth Ogando-Rivas¹, Paul Castillo², Changlin Yang¹

¹UF Brain Tumor Immunotherapy Program, Preston A. Wells Center for Brain Tumor Therapy, Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, FL, USA.

Molecular therapy. Methods & clinical development

|February 8, 2024

概括

这项研究开发了一种基于mRNA的新方法,使用抗原呈现细胞产生SARS-CoV-2特异性T细胞. 这种方法有效地激活免疫功能低下个体的T细胞,提供对COVID-19变种的潜在保护.

科学领域:

免疫学免疫学免疫学
疫苗学疫苗学疫苗学
病毒学病毒学

背景情况:

在全球范围内,COVID-19已经造成了数百万人的死亡.
目前的mRNA疫苗可以保护免疫能力强的个体,但在免疫能力低下的人群中效果较差.
患有原发性免疫缺陷,癌症或移植受体的患者往往无法对疫苗产生足够的免疫反应.

研究的目的:

开发一种针对结构性SARS-CoV-2抗原的替代COVID-19疫苗策略.
在无法对当前疫苗做出反应的个体中激活和扩展SARS-CoV-2特定的T细胞.
评估mRNA载荷抗原呈现细胞对T细胞激活的疗效.

主要方法:

使用了循环的人类抗原呈现细胞,用SARS-CoV-2结构蛋白mRNA (Spike, Membrane, Nucleocapsid, Envelope) 进行电穿孔.
在抗原重新挑战时通过Th1型细胞因子和细胞分解酶分泌评估T细胞激活和扩张.
分析了SARS-CoV-2 特定的T细胞受体β (TCRβ) 谱.

主要成果:

在三次刺激后70%的健康捐赠者和两次刺激后100%的康复患者中产生了SARS-CoV-2特异性T细胞.
鉴定了T细胞,特异于Spike糖蛋白的保存,低突变区域,表明潜在的对变体的交叉保护.
证明了mRNA载荷抗原呈现细胞在激活和扩展抗原特异性T细胞方面的有效性.

结论:

装有SARS-CoV-2mRNA的抗原呈现细胞在产生抗原特异性T细胞方面有效.
这种方法为免疫力低下的个体提供了一个有希望的替代方案,这些个体对当前的COVID-19疫苗反应不佳.
该策略有可能对新出现的SARS-CoV-2变种进行保护,这是由于被准的保存遗传区域.

关键词:

基于RNA的免疫疗法这就是SARS-CoV-2病毒.采用T细胞的采用T细胞呈现抗原的细胞.过度变异的地区是低变异的地区.

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