PMID- 36986686
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230331
IS  - 1999-4923 (Print)
IS  - 1999-4923 (Electronic)
IS  - 1999-4923 (Linking)
VI  - 15
IP  - 3
DP  - 2023 Mar 2
TI  - CuMV VLPs Containing the RBM from SARS-CoV-2 Spike Protein Drive Dendritic Cell 
      Activation and Th1 Polarization.
LID - 10.3390/pharmaceutics15030825 [doi]
LID - 825
AB  - 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' 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.
FAU - Sebastiao, Ana Isabel
AU  - Sebastiao AI
AUID- ORCID: 0000-0002-1687-2968
AD  - Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal.
AD  - Center for Innovative Biomedicine and Biotechnology (CIBB), University of 
      Coimbra, 3000-548 Coimbra, Portugal.
FAU - Mateus, Daniela
AU  - Mateus D
AUID- ORCID: 0000-0002-7511-4358
AD  - Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal.
AD  - Center for Innovative Biomedicine and Biotechnology (CIBB), University of 
      Coimbra, 3000-548 Coimbra, Portugal.
FAU - Carrascal, Mylene A
AU  - Carrascal MA
AUID- ORCID: 0000-0002-3391-543X
AD  - Tecnimede Group, 2710-089 Sintra, Portugal.
FAU - Sousa, Catia
AU  - Sousa C
AUID- ORCID: 0000-0002-9802-5657
AD  - Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal.
AD  - Center for Innovative Biomedicine and Biotechnology (CIBB), University of 
      Coimbra, 3000-548 Coimbra, Portugal.
FAU - Cortes, Luisa
AU  - Cortes L
AUID- ORCID: 0000-0001-5292-4369
AD  - Center for Innovative Biomedicine and Biotechnology (CIBB), University of 
      Coimbra, 3000-548 Coimbra, Portugal.
FAU - Bachmann, Martin F
AU  - Bachmann MF
AUID- ORCID: 0000-0003-4370-2099
AD  - Department of BioMedical Research, University of Bern, 3012 Bern, Switzerland.
FAU - do Carmo, Analia
AU  - do Carmo A
AUID- ORCID: 0000-0002-7704-4736
AD  - Clinical Pathology Department, Centro Hospitalar e Universitario de Coimbra, 
      3000-075 Coimbra, Portugal.
FAU - Matos, Ana Miguel
AU  - Matos AM
AUID- ORCID: 0000-0001-5764-0023
AD  - Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal.
AD  - Chemical Engineering Processes and Forest Products Research Center, CIEPQPF, 
      Faculty of Sciences and Technology, University of Coimbra, 3030-790 Coimbra, 
      Portugal.
FAU - Sales, Maria Goreti F
AU  - Sales MGF
AUID- ORCID: 0000-0001-9936-7336
AD  - BioMark@UC/CEB-LABBELS, Department of Chemical Engineering, Faculty of Sciences 
      and Technology, University of Coimbra, 3030-790 Coimbra, Portugal.
FAU - Cruz, Maria Teresa
AU  - Cruz MT
AUID- ORCID: 0000-0001-9846-6754
AD  - Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal.
AD  - Center for Innovative Biomedicine and Biotechnology (CIBB), University of 
      Coimbra, 3000-548 Coimbra, Portugal.
LA  - eng
GR  - POCI-01-02B7-FEDER-069745/European Regional Development Fund/
PT  - Journal Article
DEP - 20230302
PL  - Switzerland
TA  - Pharmaceutics
JT  - Pharmaceutics
JID - 101534003
PMC - PMC10055701
OTO - NOTNLM
OT  - COVID-19
OT  - SARS-CoV-2
OT  - adaptive immune response
OT  - dendritic cells
OT  - memory T cell
OT  - virus-like particles
COIS- The authors declare that they have no competing interests. The company had no 
      role in the design of the study; in the collection, analyses, or interpretation 
      of data; in the writing of the manuscript, and in the decision to publish the 
      results.
EDAT- 2023/03/30 06:00
MHDA- 2023/03/30 06:01
PMCR- 2023/03/02
CRDT- 2023/03/29 02:02
PHST- 2023/01/03 00:00 [received]
PHST- 2023/02/17 00:00 [revised]
PHST- 2023/02/20 00:00 [accepted]
PHST- 2023/03/30 06:01 [medline]
PHST- 2023/03/29 02:02 [entrez]
PHST- 2023/03/30 06:00 [pubmed]
PHST- 2023/03/02 00:00 [pmc-release]
AID - pharmaceutics15030825 [pii]
AID - pharmaceutics-15-00825 [pii]
AID - 10.3390/pharmaceutics15030825 [doi]
PST - epublish
SO  - Pharmaceutics. 2023 Mar 2;15(3):825. doi: 10.3390/pharmaceutics15030825.