scholarly journals Murine Dendritic Cells for Immunotherapy and Vaccine Development: Generation, Optimization and Transduction

2020 ◽  
Vol 7 (2) ◽  
pp. 22-27
Author(s):  
Mona Sadat Larijani ◽  
Maryam Mashhadi Abolghasem Shirazi ◽  
Amitis Ramezani ◽  
Azam Bolhassani ◽  
Mohammad Hassan Pouriayevali ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Vaccine Development

scholarly journals Dendritic Cells/Macrophages-Targeting Feature of Ebola Glycoprotein and its Potential as Immunological Facilitator for Antiviral Vaccine Approach

2019 ◽  
Vol 7 (10) ◽  
pp. 402
Author(s):  
Titus Abiola Olukitibi ◽  
Zhujun Ao ◽  
Mona Mahmoudi ◽  
Gary A. Kobinger ◽  
Xiaojian Yao
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Ebola Virus ◽  
Vaccine Development ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Immunological Approach ◽  
Vaccine Approach ◽  
Acquired Immune Responses ◽  
Diverse Virus

In the prevention of epidemic and pandemic viral infection, the use of the antiviral vaccine has been the most successful biotechnological and biomedical approach. In recent times, vaccine development studies have focused on recruiting and targeting immunogens to dendritic cells (DCs) and macrophages to induce innate and adaptive immune responses. Interestingly, Ebola virus (EBOV) glycoprotein (GP) has a strong binding affinity with DCs and macrophages. Shreds of evidence have also shown that the interaction between EBOV GP with DCs and macrophages leads to massive recruitment of DCs and macrophages capable of regulating innate and adaptive immune responses. Therefore, studies for the development of vaccine can utilize the affinity between EBOV GP and DCs/macrophages as a novel immunological approach to induce both innate and acquired immune responses. In this review, we will discuss the unique features of EBOV GP to target the DC, and its potential to elicit strong immune responses while targeting DCs/macrophages. This review hopes to suggest and stimulate thoughts of developing a stronger and effective DC-targeting vaccine for diverse virus infection using EBOV GP.

scholarly journals Internalization and endosomal degradation of receptor-bound antigens regulate the efficiency of cross presentation by human dendritic cells

Blood ◽  
2012 ◽  
Vol 120 (10) ◽  
pp. 2011-2020 ◽  
Author(s):  
Bithi Chatterjee ◽  
Anna Smed-Sörensen ◽  
Lillian Cohn ◽  
Cécile Chalouni ◽  
Richard Vandlen ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Vaccine Development ◽  
Mannose Receptor ◽  
Antigen Delivery ◽  
Cross Presentation ◽  
Late Endosomes ◽  
Early Endosomes ◽  
Antibody Conjugates ◽  
Human Dendritic Cells ◽  
Endocytic Compartments

Abstract Dendritic cells (DCs) can capture extracellular antigens and load resultant peptides on to MHC class I molecules, a process termed cross presentation. The mechanisms of cross presentation remain incompletely understood, particularly in primary human DCs. One unknown is the extent to which antigen delivery to distinct endocytic compartments determines cross presentation efficiency, possibly by influencing antigen egress to the cytosol. We addressed the problem directly and quantitatively by comparing the cross presentation of identical antigens conjugated with antibodies against different DC receptors that are targeted to early or late endosomes at distinct efficiencies. In human BDCA1+ and monocyte-derived DCs, CD40 and mannose receptor targeted antibody conjugates to early endosomes, whereas DEC205 targeted antigen primarily to late compartments. Surprisingly, the receptor least efficient at internalization, CD40, was the most efficient at cross presentation. This did not reflect DC activation by CD40, but rather its relatively poor uptake or intra-endosomal degradation compared with mannose receptor or DEC205. Thus, although both early and late endosomes appear to support cross presentation in human DCs, internalization efficiency, especially to late compartments, may be a negative predictor of activity when selecting receptors for vaccine development.

scholarly journals Soluble proteins delivered to dendritic cells via pH-sensitive liposomes induce primary cytotoxic T lymphocyte responses in vitro.

1992 ◽  
Vol 175 (2) ◽  
pp. 609-612 ◽  
Author(s):  
S Nair ◽  
F Zhou ◽  
R Reddy ◽  
L Huang ◽  
B T Rouse
Keyword(s):  
Dendritic Cells ◽  
T Lymphocyte ◽  
Antigen Processing ◽  
Vaccine Development ◽  
Cytotoxic T Lymphocyte ◽  
Present Report ◽  
Soluble Proteins ◽  
Ph Sensitive ◽  
Ctl Response

Effective immunity to many infectious agents, particularly viruses, requires a CD8+ cytotoxic T lymphocyte (CTL) response. Understanding how to achieve CTL induction with soluble proteins is important for vaccine development since such antigens are usually not processed appropriately to induce CTL. In the present report, we have demonstrated that a potent primary CTL response against a soluble protein can be achieved by delivering antigen in pH-sensitive liposomes to dendritic cells (DC) either in vivo or in vitro. Since the pH-sensitive liposome delivery system is efficient and easy to use, the approach promises to be valuable both in the study of basic mechanisms in antigen processing, and as a practical means of immunization.

scholarly journals Activation of Tumor Antigen-Specific Cytotoxic T Lymphocytes (CTLs) by Human Dendritic Cells Infected with an Attenuated Influenza A Virus Expressing a CTL Epitope Derived from the HER-2/neu Proto-Oncogene

2003 ◽  
Vol 77 (13) ◽  
pp. 7411-7424 ◽  
Author(s):  
Clay L. Efferson ◽  
Jeanne Schickli ◽  
Byung Kyum Ko ◽  
Kouichiro Kawano ◽  
Sara Mouzi ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Influenza A Virus ◽  
Tumor Antigen ◽  
Influenza A ◽  
Vaccine Development ◽  
Interleukin 2 ◽  
Transduction Efficiency ◽  
Ctl Epitope ◽  
The Poor ◽  
Her 2

ABSTRACT The development of cancer vaccines requires approaches to induce expansion and functional differentiation of tumor antigen-specific cytotoxic T lymphocyte (CTL) effectors which posses cytolytic capability and produce cytokines. Efficient induction of such cells is hindered by the poor immunogenicity of tumor antigens and by the poor transduction efficiency of dendritic cells (DCs) with current nonreplicating vectors. We have investigated the use of influenza A virus, a potent viral inducer of CTLs, as a vector expressing the immunodominant HER-2 CTL epitope KIF (E75). For this purpose, an attenuated influenza A/PR8/34 virus with a truncated nonstructural (NS1) gene was generated containing the E75 epitope in its neuraminidase protein (KIF-NS virus). Stimulation of peripheral blood mononuclear cells from healthy donors and of tumor-associated lymphocytes from ovarian and breast cancer patients with DCs infected with KIF-NS virus (KIF-NS DC) induced CTLs that specifically recognized the peptide KIF and HER-2-expressing tumors in cytotoxicity assays and secreted gamma interferon (IFN-γ) and interleukin-2 at recall with peptide. Priming with KIF-NS DCs increased the number of E75+ CD45RO+ cells by more than 10-fold compared to nonstimulated cells. In addition, KIF-NS virus induced high levels of IFN-α in DCs. This is the first report demonstrating induction of human epitope-specific CTLs against a tumor-associated antigen with a live attenuated recombinant influenza virus vector. Such vectors may provide a novel approach for tumor antigen delivery, lymphocyte activation, and differentiation in human cancer vaccine development.

scholarly journals Suppression of Endogenous IL-10 Gene Expression in Dendritic Cells Enhances Antigen Presentation for Specific Th1 Induction: Potential for Cellular Vaccine Development

2000 ◽  
Vol 164 (8) ◽  
pp. 4212-4219 ◽  
Author(s):  
Joseph U. Igietseme ◽  
Godwin A. Ananaba ◽  
Jacqueline Bolier ◽  
Samera Bowers ◽  
Terri Moore ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dendritic Cells ◽  
Antigen Presentation ◽  
Vaccine Development

scholarly journals Burkholderia pseudomalleiProteins Presented by Monocyte-Derived Dendritic Cells Stimulate Human Memory T CellsIn Vitro

2010 ◽  
Vol 79 (1) ◽  
pp. 305-313 ◽  
Author(s):  
Patcharaporn Tippayawat ◽  
Maneerat Pinsiri ◽  
Darawan Rinchai ◽  
Donporn Riyapa ◽  
Amornrat Romphruk ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Immune Responses ◽  
Human Cell ◽  
Vaccine Development ◽  
Repeat Sequence ◽  
Effective Vaccine ◽  
Healthy Individuals ◽  
Peptide Epitopes

ABSTRACTMelioidosis is a severe infectious disease caused by the saprophytic facultative intracellular pathogenBurkholderia pseudomallei. The disease is endemic in Southeast Asia and Northern Australia, and no effective vaccine exists. To describe human cell-mediated immune responses toB. pseudomalleiand to identify candidate antigens for vaccine development, the ability of antigen-pulsed monocyte-derived dendritic cells (moDCs) to trigger autologous T-cell responses toB. pseudomalleiand its products was tested. moDCs were prepared from healthy individuals exposed or not exposed toB. pseudomallei, based on serological evidence. These were pulsed with heat-killedB. pseudomalleior purified antigens, including ABC transporters (LolC, OppA, and PotF), Bsa type III secreted proteins (BipD and BopE), tandem repeat sequence-containing proteins (Rp1 and Rp2), flagellin, and heat shock proteins (Hsp60 and Hsp70), prior to being mixed with autologous T-cell populations. After pulsing of cells with either heat-killedB. pseudomallei, LolC, or Rp2, coculturing the antigen-pulsed moDCs with T cells elicited gamma interferon production from CD4+T cells from seropositive donors at levels greater than those for seronegative donors. These antigens also induced granzyme B (cytotoxic) responses from CD8+T cells. Activation of antigen-specific CD4+T cells required direct contact with moDCs and was therefore not dependent on soluble mediators. Rp peptide epitopes recognized by T cells in healthy individuals were identified. Our study provides valuable novel data on the induction of human cell-mediated immune responses toB. pseudomalleiand its protein antigens that may be exploited in the rational development of vaccines to combat melioidosis.

scholarly journals Role of Dendritic Cells in Antibody-Dependent Enhancement of Dengue Virus Infection

2008 ◽  
Vol 82 (8) ◽  
pp. 3939-3951 ◽  
Author(s):  
Kobporn Boonnak ◽  
Bonnie M. Slike ◽  
Timothy H. Burgess ◽  
Randall M. Mason ◽  
Shuenn-Jue Wu ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Complex Disease ◽  
Vaccine Development ◽  
De Novo ◽  
Surface Expression ◽  
Necrosis Factor Alpha ◽  
Antibody Dependent Enhancement ◽  
Cellular Targets ◽  
Gamma Receptor

ABSTRACT Dengue viruses (DV), composed of four distinct serotypes (DV1 to DV4), cause 50 to 100 million infections annually. Durable homotypic immunity follows infection but may predispose to severe subsequent heterotypic infections, a risk conferred in part by the immune response itself. Antibody-dependent enhancement (ADE), a process best described in vitro, is epidemiologically linked to complicated DV infections, especially in Southeast Asia. Here we report for the first time the ADE phenomenon in primary human dendritic cells (DC), early targets of DV infection, and human cell lines bearing Fc receptors. We show that ADE is inversely correlated with surface expression of DC-SIGN (DC-specific intercellular adhesion molecule-3-grabbing nonintegrin) and requires Fc gamma receptor IIa (FcγRIIa). Mature DC exhibited ADE, whereas immature DC, expressing higher levels of DC-SIGN and similar FcγRIIa levels, did not undergo ADE. ADE results in increased intracellular de novo DV protein synthesis, increased viral RNA production and release, and increased infectivity of the supernatants in mature DC. Interestingly, tumor necrosis factor alpha and interleukin-6 (IL-6), but not IL-10 and gamma interferon, were released in the presence of dengue patient sera but generally only at enhancement titers, suggesting a signaling component of ADE. FcγRIIa inhibition with monoclonal antibodies abrogated ADE and associated downstream consequences. DV versatility in entry routes (FcγRIIa or DC-SIGN) in mature DC broadens target options and suggests additional ways for DC to contribute to the pathogenesis of severe DV infection. Studying the cellular targets of DV infection and their susceptibility to ADE will aid our understanding of complex disease and contribute to the field of vaccine development.

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