{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T05:22:15Z","timestamp":1773984135616,"version":"3.50.1"},"reference-count":56,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,3,2]],"date-time":"2023-03-02T00:00:00Z","timestamp":1677715200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Regional Development Fund","award":["POCI-01-02B7-FEDER-069745"],"award-info":[{"award-number":["POCI-01-02B7-FEDER-069745"]}]},{"name":"European Regional Development Fund","award":["UIDB\/04539\/2020"],"award-info":[{"award-number":["UIDB\/04539\/2020"]}]},{"name":"European Regional Development Fund","award":["UIDP\/04539\/2020"],"award-info":[{"award-number":["UIDP\/04539\/2020"]}]},{"name":"European Regional Development Fund","award":["LA\/P\/0058\/2020"],"award-info":[{"award-number":["LA\/P\/0058\/2020"]}]},{"name":"National Innovation Agency","award":["POCI-01-02B7-FEDER-069745"],"award-info":[{"award-number":["POCI-01-02B7-FEDER-069745"]}]},{"name":"National Innovation Agency","award":["UIDB\/04539\/2020"],"award-info":[{"award-number":["UIDB\/04539\/2020"]}]},{"name":"National Innovation Agency","award":["UIDP\/04539\/2020"],"award-info":[{"award-number":["UIDP\/04539\/2020"]}]},{"name":"National Innovation Agency","award":["LA\/P\/0058\/2020"],"award-info":[{"award-number":["LA\/P\/0058\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Dendritic cells (DCs) are the most specialized and proficient antigen-presenting cells. They bridge innate and adaptive immunity and display a powerful capacity to prime antigen-specific T cells. The interaction of DCs with the receptor-binding domain of the spike (S) protein from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a pivotal step to induce effective immunity against the S protein-based vaccination protocols, as well as the SARS-CoV-2 virus. Herein, we describe the cellular and molecular events triggered by virus-like particles (VLPs) containing the receptor-binding motif from the SARS-CoV-2 spike protein in human monocyte-derived dendritic cells, or, as controls, in the presence of the Toll-like receptors (TLR)3 and TLR7\/8 agonists, comprehending the events of dendritic cell maturation and their crosstalk with T cells. The results demonstrated that VLPs boosted the expression of major histocompatibility complex molecules and co-stimulatory receptors of DCs, indicating their maturation. Furthermore, DCs\u2019 interaction with VLPs promoted the activation of the NF-kB pathway, a very important intracellular signalling pathway responsible for triggering the expression and secretion of proinflammatory cytokines. Additionally, co-culture of DCs with T cells triggered CD4+ (mainly CD4+Tbet+) and CD8+ T cell proliferation. Our results suggested that VLPs increase cellular immunity, involving DC maturation and T cell polarization towards a type 1 T cells profile. By providing deeper insight into the mechanisms of activation and regulation of the immune system by DCs, these findings will enable the design of effective vaccines against SARS-CoV-2.<\/jats:p>","DOI":"10.3390\/pharmaceutics15030825","type":"journal-article","created":{"date-parts":[[2023,3,3]],"date-time":"2023-03-03T02:56:50Z","timestamp":1677812210000},"page":"825","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["CuMV VLPs Containing the RBM from SARS-CoV-2 Spike Protein Drive Dendritic Cell Activation and Th1 Polarization"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1687-2968","authenticated-orcid":false,"given":"Ana Isabel","family":"Sebasti\u00e3o","sequence":"first","affiliation":[{"name":"Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7511-4358","authenticated-orcid":false,"given":"Daniela","family":"Mateus","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3391-543X","authenticated-orcid":false,"given":"Myl\u00e8ne A.","family":"Carrascal","sequence":"additional","affiliation":[{"name":"Tecnimede Group, 2710-089 Sintra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9802-5657","authenticated-orcid":false,"given":"C\u00e1tia","family":"Sousa","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5292-4369","authenticated-orcid":false,"given":"Lu\u00edsa","family":"Cortes","sequence":"additional","affiliation":[{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4370-2099","authenticated-orcid":false,"given":"Martin F.","family":"Bachmann","sequence":"additional","affiliation":[{"name":"Department of BioMedical Research, University of Bern, 3012 Bern, Switzerland"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7704-4736","authenticated-orcid":false,"given":"An\u00e1lia","family":"do Carmo","sequence":"additional","affiliation":[{"name":"Clinical Pathology Department, Centro Hospitalar e Universit\u00e1rio de Coimbra, 3000-075 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5764-0023","authenticated-orcid":false,"given":"Ana Miguel","family":"Matos","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Chemical Engineering Processes and Forest Products Research Center, CIEPQPF, Faculty of Sciences and Technology, University of Coimbra, 3030-790 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9936-7336","authenticated-orcid":false,"given":"Maria Goreti F.","family":"Sales","sequence":"additional","affiliation":[{"name":"BioMark@UC\/CEB\u2014LABBELS, Department of Chemical Engineering, Faculty of Sciences and Technology, University of Coimbra, 3030-790 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9846-6754","authenticated-orcid":false,"given":"Maria Teresa","family":"Cruz","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"100736","DOI":"10.1016\/j.jbior.2020.100736","article-title":"SARS-CoV-2 pandemic: An overview","volume":"77","author":"Flacco","year":"2020","journal-title":"Adv. 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