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dc.contributor.authorZeltins, Andris
dc.contributor.authorWest, Jonathan
dc.contributor.authorZabel, Franziska
dc.contributor.authorEl Turabi, Aadil
dc.contributor.authorBalke, Ina
dc.contributor.authorHaas, Stefanie
dc.contributor.authorMaudrich, Melanie
dc.contributor.authorStorni, Federico
dc.contributor.authorEngeroff, Paul
dc.contributor.authorJennings, Gary T
dc.contributor.authorKotecha, Abhay
dc.contributor.authorStuart, David I
dc.contributor.authorFoerster, John
dc.contributor.authorBachmann, Martin F
dc.date.accessioned2019-08-13T14:30:07Z
dc.date.available2019-08-13T14:30:07Z
dc.date.issued2017-10-23
dc.identifier.citationZeltins , A , West , J , Zabel , F , El Turabi , A , Balke , I , Haas , S , Maudrich , M , Storni , F , Engeroff , P , Jennings , G T , Kotecha , A , Stuart , D I , Foerster , J & Bachmann , M F 2017 , ' Incorporation of tetanus-epitope into virus-like particles achieves vaccine responses even in older recipients in models of psoriasis, Alzheimer's and cat allergy ' npj Vaccines , vol. 2 , 30 . https://doi.org/10.1038/s41541-017-0030-8en
dc.identifier.issn2059-0105
dc.identifier.otherPURE: 260534123
dc.identifier.otherPURE UUID: e9d18eac-eff7-4152-a383-2457b989eec8
dc.identifier.otherPubMed: 29263885
dc.identifier.otherPubMedCentral: PMC5653761
dc.identifier.otherScopus: 85042174177
dc.identifier.urihttp://hdl.handle.net/10023/18307
dc.description.abstractMonoclonal antibodies are widely used to treat non-infectious conditions but are costly. Vaccines could offer a cost-effective alternative but have been limited by sub-optimal T-cell stimulation and/or weak vaccine responses in recipients, for example, in elderly patients. We have previously shown that the repetitive structure of virus-like-particles (VLPs) can effectively bypass self-tolerance in therapeutic vaccines. Their efficacy could be increased even further by the incorporation of an epitope stimulating T cell help. However, the self-assembly and stability of VLPs from envelope monomer proteins is sensitive to geometry, rendering the incorporation of foreign epitopes difficult. We here show that it is possible to engineer VLPs derived from a non human-pathogenic plant virus to incorporate a powerful T-cell-stimulatory epitope derived from Tetanus toxoid. These VLPs (termed CMVTT) retain self-assembly as well as long-term stability. Since Th cell memory to Tetanus is near universal in humans, CMVTT-based vaccines can deliver robust antibody-responses even under limiting conditions. By way of proof of concept, we tested a range of such vaccines against chronic inflammatory conditions (model: psoriasis, antigen: interleukin-17), neurodegenerative (Alzheimer's, β-amyloid), and allergic disease (cat allergy, Fel-d1), respectively. Vaccine responses were uniformly strong, selective, efficient in vivo, observed even in old mice, and employing low vaccine doses. In addition, randomly ascertained human blood cells were reactive to CMVTT-VLPs, confirming recognition of the incorporated Tetanus epitope. The CMVTT-VLP platform is adaptable to almost any antigen and its features and performance are ideally suited for the design of vaccines delivering enhanced responsiveness in aging populations.
dc.format.extent13
dc.language.isoeng
dc.relation.ispartofnpj Vaccinesen
dc.rights© The Author(s) 2017. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visithttp://creativecommons.org/licenses/by/4.0/.en
dc.subjectQR180 Immunologyen
dc.subjectRC0321 Neuroscience. Biological psychiatry. Neuropsychiatryen
dc.subjectRL Dermatologyen
dc.subjectNDASen
dc.subject.lccQR180en
dc.subject.lccRC0321en
dc.subject.lccRLen
dc.titleIncorporation of tetanus-epitope into virus-like particles achieves vaccine responses even in older recipients in models of psoriasis, Alzheimer's and cat allergyen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews.School of Medicineen
dc.identifier.doihttps://doi.org/10.1038/s41541-017-0030-8
dc.description.statusPeer revieweden


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