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Cold-adapted live attenuated SARS-CoV-2 vaccine completely protects human ACE2 transgenic mice from SARS-CoV-2 infection
bioRxiv - Microbiology Pub Date : 2020-08-04 , DOI: 10.1101/2020.08.04.235689
Sang Heui Seo , Yunyueng Jang

Severe acute respiratory syndrome coronavirus (SARS-CoV-2) has infected more than 16,000,000 people and has caused the death of more than 650,000 individuals since December 2019. A safe and effective vaccine that can provide herd immunity against SARS-CoV-2 is urgently needed to stop the spread of this virus among humans. Many human viral vaccines are live attenuated forms of viruses that elicit humoral and cellular immunity. Here, we describe the development of a cold-adapted live attenuated vaccine (SARS-CoV-2/human/Korea/CNUHV03-CA22 degree celsius/2020) by gradually adapting the growth of SARS-CoV-2 from 37 degree celsius to 22 degree celsius in Vero cells. This vaccine can be potentially administered to humans through nasal spray. Its single dose was observed to strongly induce the neutralising antibody (over 640), cellular immunity, and mucosal IgA antibody in intranasally immunised K18-hACE2 mice, which are very susceptible to SARS-CoV-2 and SARS-CoV infection. The one-dose vaccinated mice were completely protected from SARS-CoV-2 infection and did not show loss of body weight, death, and the presence of virus in tissues, such as the nasal turbinates, brain, lungs, and kidneys. Taken together, the cold-adapted live attenuated SARS-CoV-2 vaccine developed by us may contribute to saving of human lives from the threat of SARS-CoV-2.

中文翻译:

适应寒冷的减毒活SARS-CoV-2疫苗可完全保护人类ACE2转基因小鼠免受SARS-CoV-2感染

自2019年12月以来,严重的急性呼吸系统综合症冠状病毒(SARS-CoV-2)感染了超过1600万人,并导致65万多人死亡。迫切需要一种安全有效的疫苗以提供抗SARS-CoV-2的成群免疫力需要制止这种病毒在人类中的传播。许多人类病毒疫苗是减毒活病毒,可引起体液和细胞免疫。在这里,我们通过逐步将SARS-CoV-2的生长温度从37摄氏度适应到22摄氏度,描述了一种适应寒冷的减毒活疫苗(SARS-CoV-2 /人类/韩国/ CNUHV03-CA22摄氏度/ 2020)的发展Vero细胞中的摄氏温度。可以通过鼻喷雾剂将该疫苗潜在地用于人类。观察到其单剂量可强烈诱导中和抗体(超过640),细胞免疫,鼻内免疫K18-hACE2小鼠中的IgA和粘膜IgA抗体,它们对SARS-CoV-2和SARS-CoV感染非常敏感。一剂疫苗的小鼠完全免受SARS-CoV-2感染,并且没有体重减轻,死亡和组织(例如鼻甲,脑,肺和肾脏)中病毒的存在。综上所述,由我们开发的经过冷适应的减毒活体SARS-CoV-2疫苗可能有助于拯救生命,免受SARS-CoV-2的威胁。
更新日期:2020-08-05
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