scholarly journals Nanoparticle-Delivered HIV Peptides to Dendritic Cells a Promising Approach to Generate a Therapeutic Vaccine

Pharmaceutics ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 656 ◽  
Author(s):  
Alba Martín-Moreno ◽  
José L. Jiménez Blanco ◽  
Jamie Mosher ◽  
Douglas R. Swanson ◽  
José M. García Fernández ◽  
...  
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Mononuclear Cells ◽  
Therapeutic Vaccine ◽  
Peptide Delivery ◽  
Antigenic Peptide ◽  
Hydroxyl Groups ◽  
Antigenic Peptides ◽  
Peripheral Blood Mononuclear ◽  
Hiv 1

Finding a functional cure for HIV-1 infection will markedly decrease the social and economic burden of this disease. In this work, we have taken advantage of the antigen presenting cell role of human dendritic cells (DCs) to try to induce an immune response to HIV-derived peptide delivered to DCs using two different polycationic nanoparticles: a G4 PAMAM dendrimer modified to a 70/30 ratio of hydroxyl groups/amines and a cyclodextrin derivative. We have studied peptide delivery using a fluorescence peptide and have studied the immune response generation by cytokine determination and flow cytometry. We have found a robust delivery of the antigenic peptide to DCs and activated dendritic cell-mediated peripheral blood mononuclear cells (PBMCs) proliferation using the mixed lymphocyte reaction. However, no expression of markers indicating activation of either B or T lymphocytes was observed. Moreover, the release of the pro-inflammatory cytokine TNF-α or IL-2 was only observed when DCs treated with either the dendrimer or the dendriplex containing the peptide. Antigenic peptide delivery to DCs is a promising approach to generate a vaccine against HIV-1 infection. However, more studies, including the simultaneous delivery of several antigenic peptides from different viral proteins, can markedly improve the immune response.

scholarly journals Insight in miRNome of Long-Term Non-Progressors and Elite Controllers Exposes Potential RNAi Role in Restraining HIV-1 Infection

2020 ◽  
Vol 9 (8) ◽  
pp. 2452
Author(s):  
Rubén Ayala-Suárez ◽  
Francisco Díez-Fuertes ◽  
Esther Calonge ◽  
Humberto Erick De La Torre Tarazona ◽  
María Gracia-Ruíz de Alda ◽  
...  
Keyword(s):  
Immune Response ◽  
Mononuclear Cells ◽  
Elite Controllers ◽  
Peripheral Blood Mononuclear ◽  
Extreme Phenotypes ◽  
Blood Mononuclear Cells ◽  
Before And After ◽  
Anti Hiv ◽  
Hiv 1

Long-term non-progressors (LTNP) and elite controllers (EC) represent spontaneous natural models of efficient HIV-1 response in the absence of treatment. The main purposes of this work are to describe the miRNome of HIV-1 infected patients with different extreme phenotypes and identify potentially altered pathways regulated by differentially expressed (DE) miRNAs. The miRNomes from peripheral blood mononuclear cells (PBMCs) of dual phenotype EC-LTNP or LTNP with detectable viremia and HIV-infected patients with typical progression before and after treatment, were obtained through miRNA-Seq and compared among them. The administration of treatment produces 18 DE miRNAs in typical progressors. LTNP condition shows 14 DE miRNA when compared to typical progressors, allowing LTNP phenotype differentiation. A set of four miRNAs: miR-144-3p, miR-18a-5p, miR-451a, and miR-324 is strongly downregulated in LTNP and related to protein regulation as AKT, mTOR, ERK or IKK, involved in immune response pathways. Deregulation of 28 miRNA is observed between EC-LTNP and viremic-LTNP, including previously described anti-HIV miRNAs: miR-29a, associated with LTNP phenotype, and miR-155, targeting different pre-integration complexes such as ADAM10 and TNPO3. A holistic perspective of the changes observed in the miRNome of patients with different phenotypes of HIV-control and non-progression is provided.

scholarly journals Saquinavir Inhibits Early Events Associated with Establishment of HIV-1 Infection: Potential Role for Protease Inhibitors in Prevention

2012 ◽  
Vol 56 (8) ◽  
pp. 4381-4390 ◽  
Author(s):  
Martha Stefanidou ◽  
Carolina Herrera ◽  
Naomi Armanasco ◽  
Robin J. Shattock
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Highly Active Antiretroviral Therapy ◽  
Mononuclear Cells ◽  
Productive Infection ◽  
Dependent Manner ◽  
Peripheral Blood Mononuclear ◽  
Cellular Models ◽  
Hiv 1

ABSTRACTThe maturation of newly formed human immunodeficiency virus type 1 (HIV-1) virions is a critical step for the establishment of productive infection. We investigated the potential of saquinavir (SQV), a protease inhibitor (PI) used in highly active antiretroviral therapy (HAART), as a candidate microbicide. SQV inhibited replication of clade B and clade C isolates in a dose-dependent manner in all cellular models tested: PM-1 CD4 T cells, peripheral blood mononuclear cells (PBMCs), monocyte-derived macrophages (MDMs), and immature monocyte-derived dendritic cells (iMDDCs). SQV also inhibited production of infectious virus in cervical, penile, and colorectal explants cocultured with T cells. Moreover, SQV demonstrated inhibitory potency againsttransinfection of T cells byin vitro-derived dendritic cells and by primary dendritic cells that emigrate from penile and cervical tissue explants. No cellular or tissue toxicity was detected in the presence of SQV, suggesting that this drug could be considered for development as a component of an effective microbicide, capable of blocking viral maturation and transmission of HIV-1 at mucosal surfaces.

scholarly journals IMMU-22. PHASE IB IMMUNOTHERAPY CLINICAL TRIAL WITH THE USE OF AUTOLOGOUS DENDRITIC CELLS PULSED WITH AN ALLOGENIC TUMORAL CELL LINES LYSATE IN PATIENTS WITH NEWLY DIAGNOSED DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG)

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii364-iii364
Author(s):  
Andres Morales La Madrid ◽  
Jaume Mora ◽  
Ofelia Cruz ◽  
Vicente Santa-Maria Lopez ◽  
Sara Perez-Jaume ◽  
...  
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Mononuclear Cells ◽  
Tumor Antigens ◽  
Progression Free Survival ◽  
Diffuse Intrinsic Pontine Glioma ◽  
Newly Diagnosed ◽  
Tumor Lysate ◽  
Pontine Glioma ◽  
Peripheral Blood Mononuclear

Abstract BACKGROUND Diffuse intrinsic pontine glioma (DIPG) is a lethal condition, and therefore novel approaches are needed. Monocyte-derived dendritic cells (mDCs) pulsed with tumor antigens, as professional antigen-presenting cells, are a promising strategy for immunotherapy of invasive brain tumors. METHODS Our Ib pilot study explored the use of immunotherapy with mDCs for the treatment of newly diagnosed DIPG. Patient′s mDCs were extracted after irradiation and were primed with an allogenic tumor lysate from five patients with K27M-mutated DIPGs. The principal goal of this study was to establish the feasibility and safety of the intradermic administration of these mDC vaccines in patients with DIPG. In the absence of progression, patients received maintenance boosts of tumor lysate. Additionally, we evaluated the non-specific and antitumoral immune response generated in peripheral blood mononuclear cells (PBMC) and in cerebrospinal fluid (CSF) cells. RESULTS Nine patients were included in the study (2016–2018). Vaccines fabrication was feasible and administered in all cases without grade 3 or 4 toxicities. KLH (9/9 patients) and antitumor (8/9 patients) specific responses were identified in PBMC. Immunological responses were also confirmed in T-lymphocytes from the CSF of two patients. Twenty-four month overall survival and progression free survival was 33.3% (95 % CI 13.2% to 84.0 %) and zero, respectively. DISCUSSION These results demonstrate that mDC vaccination is feasible, safe, and generates a DIPG-specific immune response detected in PBMC and CSF. There was a trend in improved OS when compared to historic controls. This strategy shows a promising immunotherapy backbone for future combination schemas.

scholarly journals Naturally Derived Anti-HIV Polysaccharide Peptide (PSP) Triggers a Toll-Like Receptor 4-Dependent Antiviral Immune Response

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Madeline Rodríguez-Valentín ◽  
Sheila López ◽  
Mariela Rivera ◽  
Eddy Ríos-Olivares ◽  
Luis Cubano ◽  
...  
Keyword(s):  
Immune Response ◽  
Drug Targets ◽  
Mononuclear Cells ◽  
Toll Like Receptor ◽  
Viral Inhibition ◽  
Toll Like Receptor 4 ◽  
Peripheral Blood Mononuclear ◽  
Antiviral Immune Response ◽  
Anti Hiv ◽  
Hiv 1

Aim. Intense interest remains in the identification of compounds to reduce human immunodeficiency virus type 1 (HIV-1) replication. Coriolus versicolor’s polysaccharide peptide (PSP) has been demonstrated to possess immunomodulatory properties with the ability to activate an innate immune response through Toll-like receptor 4 (TLR4) showing insignificant toxicity. This study sought to determine the potential use of PSP as an anti-HIV agent and whether its antiviral immune response was TLR4 dependent. Materials and Methods. HIV-1 p24 and anti-HIV chemokine release was assessed in HIV-positive (HIV+) THP1 cells and validated in HIV+ peripheral blood mononuclear cells (PBMCs), to determine PSP antiviral activity. The involvement of TLR4 activation in PSP anti-HIV activity was evaluated by inhibition. Results. PSP showed a promising potential as an anti-HIV agent, by downregulating viral replication and promoting the upregulation of specific antiviral chemokines (RANTES, MIP-1α/β, and SDF-1α) known to block HIV-1 coreceptors in THP1 cells and human PBMCs. PSP produced a 61% viral inhibition after PSP treatment in HIV-1-infected THP1 cells. Additionally, PSP upregulated the expression of TLR4 and TLR4 inhibition led to countereffects in chemokine expression and HIV-1 replication. Conclusion. Taken together, these findings put forward the first evidence that PSP exerts an anti-HIV activity mediated by TLR4 and key antiviral chemokines. Elucidating these new molecular mediators may reveal additional drug targets and open novel therapeutic avenues for HIV-1 infection.

Dendritic Cells Tranfected with CML-28 cDNA Induce CML28-Specific Cytotoxic T Cells.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5248-5248
Author(s):  
Hongsheng Zhou ◽  
Donghua Zhang ◽  
Yaya Wang ◽  
Yi Xiao ◽  
Wei Huang ◽  
...  
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Tumor Antigen ◽  
Mononuclear Cells ◽  
Cytotoxic T Cells ◽  
Lymphocytic Leukemia ◽  
Myelogenous Leukemia ◽  
Target Cells ◽  
Peripheral Blood Mononuclear

Abstract Dendritic cells (DC) are the most potent antigen-presenting cells known; the use of DC loaded with tumor antigen is one of the most promising approaches to induce specific immune response. CML28 is an attractive candidate. According to the published article and our following study, CML28 is a broadly immunogenic antigen, which is overexpessed in leukemia cells, including acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL) and chronic myelogenous leukemia (CML); but not in normal hematopoietic tissues or other normal tissue, with the exception of testis. In our study, DCs were generated from peripheral blood mononuclear cells (PBMC) by culture with GM-CSF, IL-4 and TNF-α. The full CML28 cDNA was amplified from K562 cell and then cloned into plasmid pcDNA3.1 HisA. Load DC with the constructed plasmid pcDNA3.1 HisA-CML28 by electroporation. The results of FACS analysis and Western Blot respectively demonstrate that the plasmid transfected DC retain immunophenotypical characteristics and can express the fusion protein CML28-His. Cytotoxic T lymphocytes (CTL) were generated from autologous PBMC stimulated by the transfected DCs. Cytoxicity assay in vitro revealed that CTL can recognize and lyse CML28-expressing target cells, such as the transfected DCs but not normal autologous DCs, which show that the plasmid pcDNA 3.1 HisA-CML28 transfected DC can induce CML28-specific CTL. Our studies demonstrate that CML28 can be a promising target of tumor antigen for leukemia-specific immunotherapy and DC loaded with CML28 tumor antigen can be a promising tool to induce specific anti-leukemia immune response.

scholarly journals HERV-K Modulates the Immune Response in ALS Patients

2021 ◽  
Vol 9 (8) ◽  
pp. 1784
Author(s):  
Giannina Arru ◽  
Grazia Galleri ◽  
Giovanni A. Deiana ◽  
Ignazio R. Zarbo ◽  
Elia Sechi ◽  
...  
Keyword(s):  
Immune Response ◽  
B Cells ◽  
Mononuclear Cells ◽  
Human Endogenous Retrovirus ◽  
Antigenic Peptides ◽  
Proinflammatory Response ◽  
Peripheral Blood Mononuclear ◽  
Great Production ◽  
Als Patients ◽  
Env Glycoprotein

Human endogenous retrovirus (HERV)-K env-su glycoprotein has been documented in amyotrophic lateral sclerosis (ALS), where HERV-K env-su 19–37 antibody levels significantly correlated with clinical measures of disease severity. Herein, we investigated further the humoral and cell-mediated immune response against specific antigenic peptides derived from HERV-K in ALS. HERV-K env glycoprotein expression on peripheral blood mononuclear cells (PBMCs) membrane and cytokines and chemokines after stimulation with HERV-K env 19–37 and HERV-K env 109–126 were quantified in patients and healthy controls (HCs). HERV-K env glycoprotein was more expressed in B cells and NK cells of ALS patients compared to HCs, whereas HERV-K env transcripts were similar in ALS and HCs. In ALS patients, specific stimulation with HERV-K env 109–126 peptide showed a higher expression of IL-6 by CD19/B cells. Both peptides, however, were able to induce a great production of IFN-γ by stimulation CD19/B cells, and yielded a higher expression of MIP-1α and a lower expression of MCP-1. HERV-K env 19–37 peptide induced a great production of TNF-α in CD8/T cells. In conclusion, we observed the ability of HERV-K to modulate the immune system, generating mediators mainly involved in proinflammatory response.

scholarly journals Profiles of Peripheral Immune Cells of Uncomplicated COVID-19 Cases with Distinct Viral RNA Shedding Periods

Viruses ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 514
Author(s):  
Denise Utami Putri ◽  
Cheng-Hui Wang ◽  
Po-Chun Tseng ◽  
Wen-Sen Lee ◽  
Fu-Lun Chen ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Cells ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
Severe Disease ◽  
Viral Rna ◽  
Disease Course ◽  
Peripheral Blood Mononuclear ◽  
Peripheral Immune Cells ◽  
Cell Profile

The heterogeneity of immune response to COVID-19 has been reported to correlate with disease severity and prognosis. While so, how the immune response progress along the period of viral RNA-shedding (VRS), which determines the infectiousness of disease, is yet to be elucidated. We aim to exhaustively evaluate the peripheral immune cells to expose the interplay of the immune system in uncomplicated COVID-19 cases with different VRS periods and dynamic changes of the immune cell profile in the prolonged cases. We prospectively recruited four uncomplicated COVID-19 patients and four healthy controls (HCs) and evaluated the immune cell profile throughout the disease course. Peripheral blood mononuclear cells (PBMCs) were collected and submitted to a multi-panel flowcytometric assay. CD19+-B cells were upregulated, while CD4, CD8, and NK cells were downregulated in prolonged VRS patients. Additionally, the pro-inflammatory-Th1 population showed downregulation, followed by improvement along the disease course, while the immunoregulatory cells showed upregulation with subsequent decline. COVID-19 patients with longer VRS expressed an immune profile comparable to those with severe disease, although they remained clinically stable. Further studies of immune signature in a larger cohort are warranted.

scholarly journals Single-cell multi-omics analysis of the immune response in COVID-19

2021 ◽  
Author(s):  
Emily Stephenson ◽  
◽  
Gary Reynolds ◽  
Rachel A. Botting ◽  
Fernando J. Calero-Nieto ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Single Cell ◽  
Mononuclear Cells ◽  
Severe Disease ◽  
Effector Memory ◽  
Peripheral Blood Mononuclear ◽  
Cross Sectional ◽  
Hematopoietic Stem ◽  
Symptomatic Disease

AbstractAnalysis of human blood immune cells provides insights into the coordinated response to viral infections such as severe acute respiratory syndrome coronavirus 2, which causes coronavirus disease 2019 (COVID-19). We performed single-cell transcriptome, surface proteome and T and B lymphocyte antigen receptor analyses of over 780,000 peripheral blood mononuclear cells from a cross-sectional cohort of 130 patients with varying severities of COVID-19. We identified expansion of nonclassical monocytes expressing complement transcripts (CD16+C1QA/B/C+) that sequester platelets and were predicted to replenish the alveolar macrophage pool in COVID-19. Early, uncommitted CD34+ hematopoietic stem/progenitor cells were primed toward megakaryopoiesis, accompanied by expanded megakaryocyte-committed progenitors and increased platelet activation. Clonally expanded CD8+ T cells and an increased ratio of CD8+ effector T cells to effector memory T cells characterized severe disease, while circulating follicular helper T cells accompanied mild disease. We observed a relative loss of IgA2 in symptomatic disease despite an overall expansion of plasmablasts and plasma cells. Our study highlights the coordinated immune response that contributes to COVID-19 pathogenesis and reveals discrete cellular components that can be targeted for therapy.

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