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针对 COVID-19 的 DNA 疫苗候选物的免疫原性。

Immunogenicity of a DNA vaccine candidate for COVID-19.

机构信息

Inovio Pharmaceuticals, Plymouth Meeting, Philadelphia, PA, 19462, USA.

Vaccine and Immunotherapy Center, Wistar Institute, Philadelphia, PA, 19104, USA.

出版信息

Nat Commun. 2020 May 20;11(1):2601. doi: 10.1038/s41467-020-16505-0.

Abstract

The coronavirus family member, SARS-CoV-2 has been identified as the causal agent for the pandemic viral pneumonia disease, COVID-19. At this time, no vaccine is available to control further dissemination of the disease. We have previously engineered a synthetic DNA vaccine targeting the MERS coronavirus Spike (S) protein, the major surface antigen of coronaviruses, which is currently in clinical study. Here we build on this prior experience to generate a synthetic DNA-based vaccine candidate targeting SARS-CoV-2 S protein. The engineered construct, INO-4800, results in robust expression of the S protein in vitro. Following immunization of mice and guinea pigs with INO-4800 we measure antigen-specific T cell responses, functional antibodies which neutralize the SARS-CoV-2 infection and block Spike protein binding to the ACE2 receptor, and biodistribution of SARS-CoV-2 targeting antibodies to the lungs. This preliminary dataset identifies INO-4800 as a potential COVID-19 vaccine candidate, supporting further translational study.

摘要

冠状病毒家族成员 SARS-CoV-2 已被确定为导致病毒性肺炎疾病 COVID-19 的病原体。目前,尚无疫苗可用于控制该疾病的进一步传播。我们之前曾设计了一种针对 MERS 冠状病毒刺突(S)蛋白的合成 DNA 疫苗,该蛋白是冠状病毒的主要表面抗原,目前正在进行临床研究。在此基础上,我们生成了一种针对 SARS-CoV-2 S 蛋白的基于合成 DNA 的候选疫苗。该工程构建体 INO-4800 可在体外大量表达 S 蛋白。INO-4800 免疫接种小鼠和豚鼠后,我们测量了抗原特异性 T 细胞反应、中和 SARS-CoV-2 感染并阻断 Spike 蛋白与 ACE2 受体结合的功能抗体,以及针对肺部的 SARS-CoV-2 靶向抗体的生物分布。这个初步数据集将 INO-4800 确定为一种有潜力的 COVID-19 疫苗候选物,支持进一步的转化研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1643/7239918/ab41b38792f2/41467_2020_16505_Fig1_HTML.jpg

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