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Live attenuated coronavirus vaccines deficient in N7-Methyltransferase activity induce both humoral and cellular immune responses in mice.
Zhang, Zhen; Liu, Qianyun; Sun, Ying; Li, Jiali; Liu, Jiejie; Pan, Ruangang; Cao, Liu; Chen, Xianying; Li, Yingjian; Zhang, Yuzhen; Xu, Ke; Guo, Deyin; Zhou, Li; Lan, Ke; Chen, Yu.
  • Zhang Z; State Key Laboratory of Virology, Modern Virology Research Center, Institute for Vaccine Research, RNA Institute, College of Life Sciences, Wuhan University, Wuhan, People's Republic of China.
  • Liu Q; State Key Laboratory of Virology, Modern Virology Research Center, Institute for Vaccine Research, RNA Institute, College of Life Sciences, Wuhan University, Wuhan, People's Republic of China.
  • Sun Y; School of Chinese Medicine (Zhongjing School), Henan Univesity of Chinese Medicne, Zhengzhou, People's Republic of China.
  • Li J; State Key Laboratory of Virology, Modern Virology Research Center, Institute for Vaccine Research, RNA Institute, College of Life Sciences, Wuhan University, Wuhan, People's Republic of China.
  • Liu J; State Key Laboratory of Virology, Modern Virology Research Center, Institute for Vaccine Research, RNA Institute, College of Life Sciences, Wuhan University, Wuhan, People's Republic of China.
  • Pan R; State Key Laboratory of Virology, Modern Virology Research Center, Institute for Vaccine Research, RNA Institute, College of Life Sciences, Wuhan University, Wuhan, People's Republic of China.
  • Cao L; Center for Infection & Immunity Study, School of Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China.
  • Chen X; State Key Laboratory of Virology, Modern Virology Research Center, Institute for Vaccine Research, RNA Institute, College of Life Sciences, Wuhan University, Wuhan, People's Republic of China.
  • Li Y; State Key Laboratory of Virology, Modern Virology Research Center, Institute for Vaccine Research, RNA Institute, College of Life Sciences, Wuhan University, Wuhan, People's Republic of China.
  • Zhang Y; Animal Bio-Safety Level III Laboratory at Center for Animal Experiments, Wuhan University School of Medicine, Wuhan, People's Republic of China.
  • Xu K; State Key Laboratory of Virology, Modern Virology Research Center, Institute for Vaccine Research, RNA Institute, College of Life Sciences, Wuhan University, Wuhan, People's Republic of China.
  • Guo D; Center for Infection & Immunity Study, School of Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China.
  • Zhou L; State Key Laboratory of Virology, Modern Virology Research Center, Institute for Vaccine Research, RNA Institute, College of Life Sciences, Wuhan University, Wuhan, People's Republic of China.
  • Lan K; Animal Bio-Safety Level III Laboratory at Center for Animal Experiments, Wuhan University School of Medicine, Wuhan, People's Republic of China.
  • Chen Y; State Key Laboratory of Virology, Modern Virology Research Center, Institute for Vaccine Research, RNA Institute, College of Life Sciences, Wuhan University, Wuhan, People's Republic of China.
Emerg Microbes Infect ; 10(1): 1626-1637, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1348038
ABSTRACT
Coronaviruses (CoVs) can infect a variety of hosts, including humans, livestock and companion animals, and pose a serious threat to human health and the economy. The current COVID-19 pandemic, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has killed millions of people. Unfortunately, effective treatments for CoVs infection are still lacking, suggesting the importance of coronavirus vaccines. Our previous work showed that CoV nonstuctural protein 14 (nsp14) functions as (guanine-N7)-methyltransferase (N7-MTase), which is involved in RNA cap formation. Moreover, we found that N7-MTase is well conserved among different CoVs and is a universal target for developing antivirals against CoVs. Here, we show that N7-MTase of CoVs can be an ideal target for designing live attenuated vaccines. Using murine hepatitis virus strain A59 (MHV-A59), a representative and well-studied model of coronaviruses, we constructed N7-MTase-deficient recombinant MHV D330A and Y414A. These two mutants are highly attenuated in mice and exhibit similar replication efficiency to the wild-type (WT) virus in the cell culture. Furthermore, a single dose immunization of D330A or Y414A can induce long-term humoral immune responses and robust CD4+ and CD8+ T cell responses, which can provide full protection against the challenge of a lethal-dose of MHV-A59. Collectively, this study provides an ideal strategy to design live attenuated vaccines for coronavirus by abolishing viral RNA N7-MTase activity. This approach may apply to other RNA viruses that encode their own conservative viral N7-methyltransferase.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Vaccines, Attenuated / COVID-19 Vaccines / SARS-CoV-2 / COVID-19 Topics: Vaccines Limits: Animals / Humans / Male Language: English Journal: Emerg Microbes Infect Year: 2021 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Vaccines, Attenuated / COVID-19 Vaccines / SARS-CoV-2 / COVID-19 Topics: Vaccines Limits: Animals / Humans / Male Language: English Journal: Emerg Microbes Infect Year: 2021 Document Type: Article