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DOI10.1073/PNAS.2025622118
Killed whole-genome reduced-bacteria surface-expressed coronavirus fusion peptide vaccines protect against disease in a porcine model
Fabris Maeda D.L.N.; Tian D.; Yu H.; Dar N.; Rajasekaran V.; Meng S.; Mahsoub H.M.; Sooryanarain H.; Wang B.; Heffron C.L.; Hassebroek A.; LeRoith T.; Meng X.-J.; Zeichner S.L.
发表日期2021
ISSN00278424
卷号118期号:18
英文摘要As the coronavirus disease 2019 (COVID-19) pandemic rages on, it is important to explore new evolution-resistant vaccine antigens and new vaccine platforms that can produce readily scalable, inexpensive vaccines with easier storage and transport. We report here a synthetic biology-based vaccine platform that employs an expression vector with an inducible gram-negative autotransporter to express vaccine antigens on the surface of genome-reduced bacteria to enhance interaction of vaccine antigen with the immune system. As a proof-of-principle, we utilized genome-reduced Escherichia coli to express SARS-CoV-2 and porcine epidemic diarrhea virus (PEDV) fusion peptide (FP) on the cell surface, and evaluated their use as killed whole-cell vaccines. The FP sequence is highly conserved across coronaviruses; the six FP core amino acid residues, along with the four adjacent residues upstream and the three residues downstream from the core, are identical between SARS-CoV-2 and PEDV. We tested the efficacy of PEDV FP and SARS-CoV-2 FP vaccines in a PEDV challenge pig model. We demonstrated that both vaccines induced potent anamnestic responses upon virus challenge, potentiated interferon-γ responses, reduced viral RNA loads in jejunum tissue, and provided significant protection against clinical disease. However, neither vaccines elicited sterilizing immunity. Since SARS-CoV-2 FP and PEDV FP vaccines provided similar clinical protection, the coronavirus FP could be a target for a broadly protective vaccine using any platform. Importantly, the genome-reduced bacterial surface-expressed vaccine platform, when using a vaccine-appropriate bacterial vector, has potential utility as an inexpensive, readily manufactured, and rapid vaccine platform for other pathogens. © 2021 National Academy of Sciences. All rights reserved.
英文关键词Fusion peptide; Genome-reduced bacteria vaccine platform; Porcine epidemic diarrhea virus (PEDV); SARS-CoV-2; Vaccine
语种英语
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/181169
作者单位Department of Pediatrics, University of Virginia, Charlottesville, VA 22908-0386, United States; Pendleton Pediatric Infectious Disease Laboratory, University of Virginia, Charlottesville, VA 22908-0386, United States; Child Health Research Center, University of Virginia, Charlottesville, VA 22908-0386, United States; Department of Biomedical Sciences and Pathobiology, Virginia Polytechnic Institute, State University, Blacksburg, VA 24061-0913, United States; Center for Emerging, Zoonotic, and Arthropod-borne Pathogens, Virginia Polytechnic Institute, State University, Blacksburg, VA 24061-0913, United States; Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, VA 22908-0386, United States
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Fabris Maeda D.L.N.,Tian D.,Yu H.,et al. Killed whole-genome reduced-bacteria surface-expressed coronavirus fusion peptide vaccines protect against disease in a porcine model[J],2021,118(18).
APA Fabris Maeda D.L.N..,Tian D..,Yu H..,Dar N..,Rajasekaran V..,...&Zeichner S.L..(2021).Killed whole-genome reduced-bacteria surface-expressed coronavirus fusion peptide vaccines protect against disease in a porcine model.Proceedings of the National Academy of Sciences of the United States of America,118(18).
MLA Fabris Maeda D.L.N.,et al."Killed whole-genome reduced-bacteria surface-expressed coronavirus fusion peptide vaccines protect against disease in a porcine model".Proceedings of the National Academy of Sciences of the United States of America 118.18(2021).
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