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Vaccines
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Vaccines Targeting Dendritic Cells
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Vaccines Targeting Dendritic Cells

A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "Cancer Vaccines and Immunotherapy".

Deadline for manuscript submissions: 31 October 2025 | Viewed by 4213

Special Issue Editors

Dr. Ronald A. Backer

E-Mail
Guest Editor
Luminex Corporation – A DiaSorin Company, Austin, TX 78727, USA
Interests: dendritic cell (subsets); cytotoxic T cells; viral infections; cancer; biomarkers
Prof. Dr. Björn E. Clausen

E-Mail Website
Guest Editor
Institute for Molecular Medicine, Paul Klein Center for Immune Intervention, University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany
Interests: Langerhans cells; dendritic cells (subsets); immune regulation; inflammation; cancer

Special Issue Information

Dear Colleagues,

Dendritic cells (DCs) act as the sentinels of the immune system and initiate and orchestrate immune responses. Current DC-based immunotherapy approaches have shown promise in cancer treatment and prevention. These approaches involve the activation of DCs following the in vitro and in vivo delivery of antigens directly to them using specialized systems such as nanoparticles or viral vectors. These strategies aim to induce humoral immunity, prime T helper cells, and/or elicit CTL responses. Broadly, the role of DCs in modulating adaptive immune responses offers new avenues for vaccine development.

This Special Issue aims to compile the latest research on the ongoing advancements in vaccines targeting DCs. We welcome the submission of reviews, research articles, and short communications that highlight recent breakthroughs in DC-targeting vaccines, as well as manuscripts addressing the challenges and limitations encountered in this field.

Dr. Ronald A. Backer
Prof. Dr. Björn E. Clausen
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Vaccines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • vaccines
  • dendritic cells
  • antigen targeting
  • immune responses
  • adjuvant
  • cancer immunotherapy
  • T cell activation

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Published Papers (4 papers)

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Research

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16 pages, 2477 KiB  
Article
Multi-Epitope DC Vaccines with Melanoma Antigens for Immunotherapy of Melanoma
by Athanasios Seretis, Lukas Amon, Christoph H. Tripp, Giuseppe Cappellano, Florian Hornsteiner, Sophie Dieckmann, Janine Vierthaler, Daniela Ortner-Tobider, Markus Kanduth, Rita Steindl, Louis Boon, Joke M. M. den Haan, Christian H. K. Lehmann, Diana Dudziak and Patrizia Stoitzner
Vaccines 2025, 13(4), 346; https://doi.org/10.3390/vaccines13040346 - 25 Mar 2025
Viewed by 414
Abstract
Background/Objectives: The revolution for the treatment of melanoma came with the approval of checkpoint blockade antibodies. However, a substantial proportion of patients show primary or secondary resistance to this type of immunotherapy, indicating the need for alternative therapeutic strategies. Dendritic cells (DCs) [...] Read more.
Background/Objectives: The revolution for the treatment of melanoma came with the approval of checkpoint blockade antibodies. However, a substantial proportion of patients show primary or secondary resistance to this type of immunotherapy, indicating the need for alternative therapeutic strategies. Dendritic cells (DCs) of the skin are prime targets for vaccination approaches due to their potential to prime naïve T cells and their accessibility. This study aimed to develop and evaluate novel vaccines targeting the C-type lectin receptor DEC-205 to deliver melanoma-associated antigenic peptides to skin DCs. Methods: We cloned MHC-I-restricted peptides from the glycoprotein (gp)10025–33 and Tyrosinase-related protein (trp)2180–188 into the DEC-205 antibody sequence with modified peptide cutting sites from the OVA257–264 SIINFEKL peptide. We tested their potential to induce CD8+ T cell responses in both in vitro and in vivo settings. Tumor growth inhibition was evaluated in the transplantable B16.OVA melanoma murine model using a multi-epitope DC-based vaccine combining both peptides. Results: The cross-presentation of both gp100 and trp2 peptides was confirmed in vivo when peptide sequences were flanked by the OVA257–264 peptide cutting sites. Moreover, the combination of both antigenic peptides into a multi-epitope DC vaccine was required to inhibit B16.OVA melanoma growth. Conclusions: Our findings suggest that a DC-targeted vaccination approach using multiple epitopes deriving from melanoma antigens could represent a promising strategy for melanoma therapy. Full article
(This article belongs to the Special Issue Vaccines Targeting Dendritic Cells)
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18 pages, 1654 KiB  
Article
The Role of Dendritic Cells in Adaptive Immune Response Induced by OVA/PDDA Nanoparticles
by Daniele R. Pereira, Yunys Pérez-Betancourt, Bianca C. L. F. Távora, Geraldo S. Magalhães, Ana Maria Carmona-Ribeiro and Eliana L. Faquim-Mauro
Vaccines 2025, 13(1), 76; https://doi.org/10.3390/vaccines13010076 - 16 Jan 2025
Cited by 1 | Viewed by 893
Abstract
Background/Objective: Cationic polymers were shown to assemble with negatively charged proteins yielding nanoparticles (NPs). Poly-diallyl-dimethyl-ammonium chloride (PDDA) combined with ovalbumin (OVA) yielded a stable colloidal dispersion (OVA/PDDA-NPs) eliciting significant anti-OVA immune response. Dendritic cells (DCs), as sentinels of foreign antigens, exert a [...] Read more.
Background/Objective: Cationic polymers were shown to assemble with negatively charged proteins yielding nanoparticles (NPs). Poly-diallyl-dimethyl-ammonium chloride (PDDA) combined with ovalbumin (OVA) yielded a stable colloidal dispersion (OVA/PDDA-NPs) eliciting significant anti-OVA immune response. Dendritic cells (DCs), as sentinels of foreign antigens, exert a crucial role in the antigen-specific immune response. Here, we aimed to evaluate the involvement of DCs in the immune response induced by OVA/PDDA. Methods: In vivo experiments were used to assess the ability of OVA/PDDA-NPs to induce anti-OVA antibodies by ELISA, as well as plasma cells and memory B cells using flow cytometry. Additionally, DC migration to draining lymph nodes following OVA/PDDA-NP immunization was evaluated by flow cytometry. In vitro experiments using bone marrow-derived DCs (BM-DCs) were used to analyze the binding and uptake of OVA/PDDA-NPs, DC maturation status, and their antigen-presenting capacity. Results: Our data confirmed the potent effect of OVA/PDDA-NPs inducing anti-OVA IgG1 and IgG2a antibodies with increased CD19+CD138+ plasma cells and CD19+CD38+CD27+ memory cells in immunized mice. OVA/PDDA-NPs induced DC maturation and migration to draining lymph nodes. The in vitro results showed higher binding and the uptake of OVA/PDDA-NPs by BM-DCs. In addition, the NPs were able to induce the upregulation of costimulatory and MHC-II molecules on DCs, as well as TNF-α and IL-12 production. Higher OVA-specific T cell proliferation was promoted by BM-DCs incubated with OVA/PDDA-NPs. Conclusions: The data showed the central role of DCs in the induction of antigen-specific immune response by OVA-PDDA-NPs, thus proving that these NPs are a potent adjuvant for subunit vaccine design. Full article
(This article belongs to the Special Issue Vaccines Targeting Dendritic Cells)
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19 pages, 6886 KiB  
Article
GSK-3β in Dendritic Cells Exerts Opposite Functions in Regulating Cross-Priming and Memory CD8 T Cell Responses Independent of β-Catenin
by Chunmei Fu, Jie Wang, Tianle Ma, Congcong Yin, Li Zhou, Björn E. Clausen, Qing-Sheng Mi and Aimin Jiang
Vaccines 2024, 12(9), 1037; https://doi.org/10.3390/vaccines12091037 - 10 Sep 2024
Viewed by 1720
Abstract
GSK-3β plays a critical role in regulating the Wnt/β-catenin signaling pathway, and manipulating GSK-3β in dendritic cells (DCs) has been shown to improve the antitumor efficacy of DC vaccines. Since the inhibition of GSK-3β leads to the activation of β-catenin, we hypothesize that [...] Read more.
GSK-3β plays a critical role in regulating the Wnt/β-catenin signaling pathway, and manipulating GSK-3β in dendritic cells (DCs) has been shown to improve the antitumor efficacy of DC vaccines. Since the inhibition of GSK-3β leads to the activation of β-catenin, we hypothesize that blocking GSK-3β in DCs negatively regulates DC-mediated CD8 T cell immunity and antitumor immunity. Using CD11c-GSK-3β−/− conditional knockout mice in which GSK-3β is genetically deleted in CD11c-expressing DCs, we surprisingly found that the deletion of GSK-3β in DCs resulted in increased antitumor immunity, which contradicted our initial expectation of reduced antitumor immunity due to the presumed upregulation of β-catenin in DCs. Indeed, we found by both Western blot and flow cytometry that the deletion of GSK-3β in DCs did not lead to augmented expression of β-catenin protein, suggesting that GSK-3β exerts its function independent of β-catenin. Supporting this notion, our single-cell RNA sequencing (scRNA-seq) analysis revealed that GSK-3β-deficient DCs exhibited distinct gene expression patterns with minimally overlapping differentially expressed genes (DEGs) compared to DCs with activated β-catenin. This suggests that the deletion of GSK-3β in DCs is unlikely to lead to upregulation of β-catenin at the transcriptional level. Consistent with enhanced antitumor immunity, we also found that CD11c-GSK-3β−/− mice exhibited significantly augmented cross-priming of antigen-specific CD8 T cells following DC-targeted vaccines. We further found that the deletion of GSK-3β in DCs completely abrogated memory CD8 T cell responses, suggesting that GSK-3β in DCs also plays a negative role in regulating the differentiation and/or maintenance of memory CD8 T cells. scRNA-seq analysis further revealed that although the deletion of GSK-3β in DCs positively regulated transcriptional programs for effector differentiation and function of primed antigen-specific CD8 T cells in CD11c-GSK-3β−/− mice during the priming phase, it resulted in significantly reduced antigen-specific memory CD8 T cells, consistent with diminished memory responses. Taken together, our data demonstrate that GSK-3β in DCs has opposite functions in regulating cross-priming and memory CD8 T cell responses, and GSK-3β exerts its functions independent of its regulation of β-catenin. These novel insights suggest that targeting GSK-3β in cancer immunotherapies must consider its dual role in CD8 T cell responses. Full article
(This article belongs to the Special Issue Vaccines Targeting Dendritic Cells)
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Review

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25 pages, 1446 KiB  
Review
Exploring CD169+ Macrophages as Key Targets for Vaccination and Therapeutic Interventions
by Rianne G. Bouma, Aru Z. Wang and Joke M. M. den Haan
Vaccines 2025, 13(3), 330; https://doi.org/10.3390/vaccines13030330 - 20 Mar 2025
Viewed by 586
Abstract
CD169 is a sialic acid-binding immunoglobulin-like lectin (Siglec-1, sialoadhesin) that is expressed by subsets of tissue-resident macrophages and circulating monocytes. This receptor interacts with α2,3-linked Neu5Ac on glycoproteins as well as glycolipids present on the surface of immune cells and pathogens. CD169-expressing macrophages [...] Read more.
CD169 is a sialic acid-binding immunoglobulin-like lectin (Siglec-1, sialoadhesin) that is expressed by subsets of tissue-resident macrophages and circulating monocytes. This receptor interacts with α2,3-linked Neu5Ac on glycoproteins as well as glycolipids present on the surface of immune cells and pathogens. CD169-expressing macrophages exert tissue-specific homeostatic functions, but they also have opposing effects on the immune response. CD169+ macrophages act as a pathogen filter, protect against infectious diseases, and enhance adaptive immunity, but at the same time pathogens also exploit them to enable further dissemination. In cancer, CD169+ macrophages in tumor-draining lymph nodes are correlated with better clinical outcomes. In inflammatory diseases, CD169 expression is upregulated on monocytes and on monocyte-derived macrophages and this correlates with the disease state. Given their role in promoting adaptive immunity, CD169+ macrophages are currently investigated as targets for vaccination strategies against cancer. In this review, we describe the studies investigating the importance of CD169 and CD169+ macrophages in several disease settings and the vaccination strategies currently under investigation. Full article
(This article belongs to the Special Issue Vaccines Targeting Dendritic Cells)
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