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诱导 gp96-Ig-S 疫苗接种小鼠肺部的 SARS-CoV-2 蛋白 S 特异性 CD8+ T 细胞。

Induction of SARS-CoV-2 Protein S-Specific CD8+ T Cells in the Lungs of gp96-Ig-S Vaccinated Mice.

机构信息

Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, FL, United States.

Heat Biologics, Inc., Morrisville, NC, United States.

出版信息

Front Immunol. 2021 Jan 26;11:602254. doi: 10.3389/fimmu.2020.602254. eCollection 2020.

Abstract

Given the aggressive spread of COVID-19-related deaths, there is an urgent public health need to support the development of vaccine candidates to rapidly improve the available control measures against SARS-CoV-2. To meet this need, we are leveraging our existing vaccine platform to target SARS-CoV-2. Here, we generated cellular heat shock chaperone protein, glycoprotein 96 (gp96), to deliver SARS-CoV-2 protein S (spike) to the immune system and to induce cell-mediated immune responses. We showed that our vaccine platform effectively stimulates a robust cellular immune response against protein S. Moreover, we confirmed that gp96-Ig, secreted from allogeneic cells expressing full-length protein S, generates powerful, protein S polyepitope-specific CD4+ and CD8+ T cell responses in both lung interstitium and airways. These findings were further strengthened by the observation that protein-S -specific CD8+ T cells were induced in human leukocyte antigen HLA-A2.1 transgenic mice thus providing encouraging translational data that the vaccine is likely to work in humans, in the context of SARS-CoV-2 antigen presentation.

摘要

鉴于与 COVID-19 相关的死亡人数不断增加,迫切需要公共卫生支持开发疫苗候选物,以迅速改善针对 SARS-CoV-2 的现有控制措施。为满足这一需求,我们正在利用现有的疫苗平台来针对 SARS-CoV-2。在这里,我们生成了细胞热休克伴侣蛋白糖蛋白 96(gp96),将 SARS-CoV-2 蛋白 S(刺突)递送到免疫系统并诱导细胞介导的免疫反应。我们表明,我们的疫苗平台有效地刺激了针对蛋白 S 的强大细胞免疫反应。此外,我们证实从表达全长蛋白 S 的同种异体细胞分泌的 gp96-Ig 在肺间质和气道中均产生了强大的、蛋白 S 多表位特异性的 CD4+和 CD8+T 细胞反应。这些发现得到了进一步加强,因为观察到在人类白细胞抗原 HLA-A2.1 转基因小鼠中诱导了蛋白-S 特异性 CD8+T 细胞,这为疫苗在 SARS-CoV-2 抗原呈递的情况下在人类中可能发挥作用提供了令人鼓舞的转化数据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2f1/7873992/b1497fef7263/fimmu-11-602254-g001.jpg

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