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补骨脂素灭活的新冠病毒疫苗及新冠病毒刺突蛋白DNA疫苗在BALB/c小鼠中的免疫原性

Immunogenicity of Adjuvanted Psoralen-Inactivated SARS-CoV-2 Vaccines and SARS-CoV-2 Spike Protein DNA Vaccines in BALB/c Mice.

作者信息

Sundaram Appavu K, Ewing Daniel, Liang Zhaodong, Jani Vihasi, Cheng Ying, Sun Peifang, Raviprakash Kanakatte, Wu Shuenn-Jue, Petrovsky Nikolai, Defang Gabriel, Williams Maya, Porter Kevin R

机构信息

Viral and Rickettsial Diseases Department, Naval Medical Research Center, Silver Spring, MD 20910, USA.

Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD 20817, USA.

出版信息

Pathogens. 2021 May 19;10(5):626. doi: 10.3390/pathogens10050626.

DOI:10.3390/pathogens10050626
PMID:34069575
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8160882/
Abstract

The development of a safe and effective vaccine to protect against COVID-19 is a global priority due to the current high SARS-CoV-2 infection rate. Currently, there are over 160 SARS-CoV-2 vaccine candidates at the clinical or pre-clinical stages of development. Of these, there are only three whole-virus vaccine candidates produced using β-propiolactone or formalin inactivation. Here, we prepared a whole-virus SARS-CoV-2 vaccine (SARS-CoV-2 PsIV) using a novel psoralen inactivation method and evaluated its immunogenicity in mice using two different adjuvants, alum and Advax-2. We compared the immunogenicity of SARS-CoV-2 PsIV against SARS-CoV-2 DNA vaccines expressing either full-length or truncated spike proteins. We also compared the psoralen-inactivated vaccine against a DNA prime, psoralen-inactivated vaccine boost regimen. After two doses, the psoralen-inactivated vaccine, when administered with alum or Advax-2 adjuvants, generated a dose-dependent neutralizing antibody responses in mice. Overall, the pattern of cytokine ELISPOT responses to antigen-stimulation observed in this study indicates that SARS-CoV-2 PsIV with the alum adjuvant promotes a Th2-type response, while SARS-CoV-2 PsIV with the Advax-2 adjuvant promotes a Th1-type response.

摘要

由于当前严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的高感染率，研发一种安全有效的预防COVID-19的疫苗成为全球优先事项。目前，有超过160种SARS-CoV-2候选疫苗正处于临床或临床前开发阶段。其中，只有三种使用β-丙内酯或福尔马林灭活制备的全病毒候选疫苗。在此，我们使用一种新型补骨脂素灭活方法制备了一种全病毒SARS-CoV-2疫苗（SARS-CoV-2 PsIV），并使用两种不同的佐剂明矾和Advax-2在小鼠中评估其免疫原性。我们比较了SARS-CoV-2 PsIV与表达全长或截短刺突蛋白的SARS-CoV-2 DNA疫苗的免疫原性。我们还比较了补骨脂素灭活疫苗与DNA初免-补骨脂素灭活疫苗加强免疫方案。两剂接种后，补骨脂素灭活疫苗与明矾或Advax-2佐剂联合使用时，在小鼠中产生了剂量依赖性的中和抗体反应。总体而言，本研究中观察到的细胞因子酶联免疫斑点（ELISPOT）对抗原刺激的反应模式表明，含明矾佐剂的SARS-CoV-2 PsIV促进Th2型反应，而含Advax-2佐剂的SARS-CoV-2 PsIV促进Th1型反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/811b/8160882/4e0a3ab52f20/pathogens-10-00626-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/811b/8160882/58a30e92bfcf/pathogens-10-00626-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/811b/8160882/440a64589d18/pathogens-10-00626-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/811b/8160882/74dc6bf49dab/pathogens-10-00626-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/811b/8160882/4a6e813c2c87/pathogens-10-00626-g004a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/811b/8160882/b3dbf5f0e5e6/pathogens-10-00626-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/811b/8160882/4e0a3ab52f20/pathogens-10-00626-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/811b/8160882/58a30e92bfcf/pathogens-10-00626-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/811b/8160882/440a64589d18/pathogens-10-00626-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/811b/8160882/74dc6bf49dab/pathogens-10-00626-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/811b/8160882/4a6e813c2c87/pathogens-10-00626-g004a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/811b/8160882/b3dbf5f0e5e6/pathogens-10-00626-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/811b/8160882/4e0a3ab52f20/pathogens-10-00626-g006.jpg

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