Killed whole-genome reduced-bacteria surface-expressed coronavirus fusion peptide vaccines protect against disease in a porcine model

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dc.contributor.authorMaeda, Denicar Lina Nascimento Fabrisen
dc.contributor.authorTian, Debinen
dc.contributor.authorYu, Hannaen
dc.contributor.authorDar, Nakulen
dc.contributor.authorRajasekaran, Vigneshen
dc.contributor.authorMeng, Sarahen
dc.contributor.authorMahsoub, Hassan M.en
dc.contributor.authorSooryanarain, Harinien
dc.contributor.authorWang, Boen
dc.contributor.authorHeffron, C. Lynnen
dc.contributor.authorHassebroek, Annaen
dc.contributor.authorLeRoith, Tanyaen
dc.contributor.authorMeng, Xiang-Jinen
dc.contributor.authorZeichner, Steven L.en
dc.date.accessioned2021-07-09T17:52:56Zen
dc.date.available2021-07-09T17:52:56Zen
dc.date.issued2021-04-15en
dc.description.abstractAs 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.en
dc.description.sponsorshipThe work was supported through the Pendleton Pediatric Infectious Disease Laboratory, by the funding provided to S.L.Z. via the McClemore Birdsong endowed chair, and by support from the University of Virginia Manning Fund for COVID-19 Research and from the Ivy Foundation. The work is also supported by the Virginia-Maryland College of Veterinary Medicine (FRS#175420), and Virginia Polytechnic Institute and State University internal funds FRS#440783.en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1073/pnas.2025622118en
dc.identifier.issue18en
dc.identifier.urihttp://hdl.handle.net/10919/104126en
dc.identifier.volume118en
dc.language.isoenen
dc.publisherNational Academy of Sciencesen
dc.rightsAttribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectvaccineen
dc.subjectgenome-reduced bacteria vaccine platformen
dc.subjectfusion peptideen
dc.subjectporcine epidemic diarrhea virus (PEDV)en
dc.subjectSARS-CoV-2en
dc.titleKilled whole-genome reduced-bacteria surface-expressed coronavirus fusion peptide vaccines protect against disease in a porcine modelen
dc.title.serialPNASen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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Scholarly Works, Biomedical Sciences and Pathobiology
Destination Area: Global Systems Science (GSS)
Scholarly Works, Center for Emerging, Zoonotic, and Arthropod-borne Pathogens (CeZAP)