气候变化领域集成服务门户(CCPortal): One or two injections of MVA-vectored vaccine shields hACE2 transgenic mice from SARS-CoV-2 upper and lower respiratory tract infection

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DOI	10.1073/pnas.2026785118
	One or two injections of MVA-vectored vaccine shields hACE2 transgenic mice from SARS-CoV-2 upper and lower respiratory tract infection
	Liu R.; Americo J.L.; Cotter C.A.; Earl P.L.; Erez N.; Peng C.; Moss B.
发表日期	2021
ISSN	00278424
卷号	118 期号:12
英文摘要	Modified vaccinia virus Ankara (MVA) is a replication-restricted smallpox vaccine, and numerous clinical studies of recombinant MVAs (rMVAs) as vectors for prevention of other infectious diseases, including COVID-19, are in progress. Here, we characterize rMVAs expressing the S protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Modifications of full-length S individually or in combination included two proline substitutions, mutations of the furin recognition site, and deletion of the endoplasmic retrieval signal. Another rMVA in which the receptor binding domain (RBD) is flanked by the signal peptide and transmembrane domains of S was also constructed. Each modified S protein was displayed on the surface of rMVA-infected cells and was recognized by anti-RBD antibody and soluble hACE2 receptor. Intramuscular injection of mice with the rMVAs induced antibodies, which neutralized a pseudovirus in vitro and, upon passive transfer, protected hACE2 transgenic mice from lethal infection with SARS-CoV-2, as well as S-specific CD3+CD8+IFNγ+ T cells. Antibody boosting occurred following a second rMVA or adjuvanted purified RBD protein. Immunity conferred by a single vaccination of hACE2 mice prevented morbidity and weight loss upon intranasal infection with SARS-CoV-2 3 wk or 7 wk later. One or two rMVA vaccinations also prevented detection of infectious SARS-CoV-2 and subgenomic viral mRNAs in the lungs and greatly reduced induction of cytokine and chemokine mRNAs. A low amount of virus was found in the nasal turbinates of only one of eight rMVA-vaccinated mice on day 2 and none later. Detection of low levels of subgenomic mRNAs in turbinates indicated that replication was aborted in immunized animals. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	COVID-19 \| coronavirus vaccine \| modified vaccinia virus Ankara \| neutralizing antibody \| transgenic mouse model
语种	英语
scopus关键词	angiotensin converting enzyme 2; CD8 antigen; chemokine; coronavirus spike glycoprotein; cytokine; furin; gamma interferon; immunoglobulin G2a; immunoglobulin G2c; membrane protein; messenger RNA; proline; receptor antibody; receptor binding domain antibody; receptor binding domain protein; receptor protein; recombinant modified vaccinia virus ankara vector; SARS-CoV-2 vaccine; unclassified drug; virus vector; ACE2 protein, human; coronavirus spike glycoprotein; DNA vaccine; immunoglobulin G; neutralizing antibody; spike protein, SARS-CoV-2; virus antibody; animal experiment; animal model; animal tissue; antigen recognition; antigen specificity; Article; body weight loss; controlled study; coronavirus disease 2019; endoplasmic reticulum; endoplasmic retrieval; female; gene construct; gene mutation; human; human cell; immune response; immunity; immunization; immunogenicity; in vitro study; infant; intranasal infection; lethality; lower respiratory tract infection; lung; morbidity; mouse; nonhuman; nose infection; passive transport; priority journal; protein expression; protein purification; pseudovirus; receptor binding; serum; severe acute respiratory syndrome; T lymphocyte; transgenic mouse; upper respiratory tract infection; vaccination; viral genomics; virus inhibition; virus neutralization; administration and dosage; animal; antibody specificity; disease model; gene expression; gene vector; genetics; immunology; metabolism; passive immunization; prevention and control; T lymphocyte subpopulation; Vaccinia virus; Angiotensin-Converting Enzyme 2; Animals; Antibodies, Neutralizing; Antibodies, Viral; Antibody Specificity; COVID-19; COVID-19 Vaccines; Disease Models, Animal; Gene Expression; Genetic Vectors; Humans; Immunization; Immunization, Passive; Immunoglobulin G; Mice; Mice, Transgenic; SARS-CoV-2; Spike Glycoprotein, Coronavirus; T-Lymphocyte Subsets; Vaccines, DNA; Vaccinia virus
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180170
作者单位	Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, United States; Department of Infectious Diseases, Israel Institute of Biological Research, Ness-Ziona, 7410001, Israel; College of Veterinary Science, China Agricultural University, Beijing, 100193, China
推荐引用方式 GB/T 7714	Liu R.,Americo J.L.,Cotter C.A.,et al. One or two injections of MVA-vectored vaccine shields hACE2 transgenic mice from SARS-CoV-2 upper and lower respiratory tract infection[J],2021,118(12).
APA	Liu R..,Americo J.L..,Cotter C.A..,Earl P.L..,Erez N..,...&Moss B..(2021).One or two injections of MVA-vectored vaccine shields hACE2 transgenic mice from SARS-CoV-2 upper and lower respiratory tract infection.Proceedings of the National Academy of Sciences of the United States of America,118(12).
MLA	Liu R.,et al."One or two injections of MVA-vectored vaccine shields hACE2 transgenic mice from SARS-CoV-2 upper and lower respiratory tract infection".Proceedings of the National Academy of Sciences of the United States of America 118.12(2021).