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dc.contributor.authorDémoulins, Thomas
dc.contributor.authorRuggli, Nicolas
dc.contributor.authorGerber, Markus
dc.contributor.authorThomann-Harwood, Lisa J
dc.contributor.authorEbensen, Thomas
dc.contributor.authorSchulze, Kai
dc.contributor.authorGuzmán, Carlos A
dc.contributor.authorMcCullough, Kenneth C
dc.date.accessioned2021-03-04T14:04:18Z
dc.date.available2021-03-04T14:04:18Z
dc.date.issued2021-01-28
dc.identifier.citationFront Immunol. 2021 Jan 28;11:622385. doi: 10.3389/fimmu.2020.622385.en_US
dc.identifier.pmid33584723
dc.identifier.doi10.3389/fimmu.2020.622385
dc.identifier.urihttp://hdl.handle.net/10033/622771
dc.description.abstractSelf-amplifying replicon RNA (RepRNA) promotes expansion of mRNA templates encoding genes of interest through their replicative nature, thus providing increased antigen payloads. RepRNA derived from the non-cytopathogenic classical swine fever virus (CSFV) targets monocytes and dendritic cells (DCs), potentially promoting prolonged antigen expression in the DCs, contrasting with cytopathogenic RepRNA. We engineered pestivirus RepRNA constructs encoding influenza virus H5N1 (A/chicken/Yamaguchi/7/2004) nucleoprotein (Rep-NP) or hemagglutinin (Rep-HA). The inherent RNase-sensitivity of RepRNA had to be circumvented to ensure efficient delivery to DCs for intracellular release and RepRNA translation; we have reported how only particular synthetic delivery vehicle formulations are appropriate. The question remained concerning RepRNA packaged in virus replicon particles (VRPs); we have now compared an efficient polyethylenimine (PEI)-based formulation (polyplex) with VRP-delivery as well as naked RepRNA co-administered with the potent bis-(3',5')-cyclic dimeric adenosine monophosphate (c-di-AMP) adjuvant. All formulations contained a Rep-HA/Rep-NP mix, to assess the breadth of both humoral and cell-mediated defences against the influenza virus antigens. Assessment employed pigs for their close immunological relationship to humans, and as natural hosts for influenza virus. Animals receiving the VRPs, as well as PEI-delivered RepRNA, displayed strong humoral and cellular responses against both HA and NP, but with VRPs proving to be more efficacious. In contrast, naked RepRNA plus c-di-AMP could induce only low-level immune responses, in one out of five pigs. In conclusion, RepRNA encoding different influenza virus antigens are efficacious for inducing both humoral and cellular immune defences in pigs. Comparisons showed that packaging within VRP remains the most efficacious for delivery leading to induction of immune defences; however, this technology necessitates employment of expensive complementing cell cultures, and VRPs do not target human cells. Therefore, choosing the appropriate synthetic delivery vehicle still offers potential for rapid vaccine design, particularly in the context of the current coronavirus pandemic.en_US
dc.language.isoenen_US
dc.publisherFrontiersen_US
dc.relation: info:eu-repo/grantAgreement/EC/FP7/601738en_US
dc.rightsopenAccessen_US
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectc-di-AMP adjuvanten_US
dc.subjecthumoral and cellular immune responseen_US
dc.subjectinfluenza vaccinesen_US
dc.subjectpolyplexesen_US
dc.subjectself-amplifying replicon RNAen_US
dc.subjectvirus replicon particleen_US
dc.titleSelf-Amplifying Pestivirus Replicon RNA Encoding Influenza Virus Nucleoprotein and Hemagglutinin Promote Humoral and Cellular Immune Responses in Pigs.en_US
dc.typeArticleen_US
dc.identifier.eissn1664-3224
dc.contributor.departmentHZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.en_US
dc.identifier.journalFrontiers in immunologyen_US
dc.source.volume11
dc.source.beginpage622385
dc.source.endpage
refterms.dateFOA2021-03-04T14:04:19Z
dc.source.journaltitleFrontiers in immunology
dc.source.countrySwitzerland


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