A randomized therapeutic vaccine trial of canarypox-HIV-pulsed dendritic cells vs. canarypox-HIV alone in HIV-1-infected patients on antiretroviral therapy

ABSTRACT We demonstrate that dendritic cells loaded in vitro with human immunodeficiency virus type 1 (HIV-1) protein-liposome complexes activate HLA class I-restricted anti-HIV-1 cytotoxic T-lymphocyte and gamma interferon (IFN-γ) responses in autologous CD8+ T cells from late-stage HIV-1-infected patients on prolonged combination drug therapy. Interleukin-12 enhanced this effect through an interleukin-2- and IFN-γ-mediated pathway. This suggests that dendritic cells from HIV-1-infected persons can be engineered to evoke stronger anti-HIV-1 CD8+ T-cell reactivity as a strategy to augment antiretroviral therapy.

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Therapeutic vaccination against HIV: current progress and future possibilities

Clinical Science ◽

10.1042/cs20050157 ◽

2005 ◽

Vol 110 (1) ◽

pp. 59-71 ◽

Cited By ~ 15

Author(s):

Rebekah L. Puls ◽

Sean Emery

Keyword(s):

Antiretroviral Therapy ◽

Viral Vectors ◽

Therapeutic Vaccine ◽

Viral Disease ◽

Clear Understanding ◽

Therapeutic Vaccination ◽

Expensive Drug ◽

Drug Regimens ◽

Anti Hiv ◽

Hiv 1

Although effective in reducing mortality, current antiretroviral therapy for HIV infection involves complex and expensive drug regimens that are toxic and difficult to take. Eradication of HIV reservoirs is not possible with existing therapies. The concept of therapeutic vaccination has been investigated to increase the potency and breadth of anti-HIV immune responses in order to delay or reduce antiretroviral therapy use. A variety of approaches targeted to both cell- and antibody-mediated immunity have been developed, including whole inactivated HIV-1, protein subunits and synthetic peptides, DNA vaccines and a number of viral vectors expressing HIV-1. These investigations have occurred in the absence of a clear understanding of disease pathogenesis or the correlates of protective immunity. At this time, there is no licensed therapeutic vaccine for any viral disease, including HIV; however, this review will consider recent progress in the field and summarize the challenges faced in the development of a therapeutic HIV vaccine.

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Assessment of migration of HIV-1-loaded dendritic cells labeled with111In-oxine used as a therapeutic vaccine in HIV-1-infected patients

Immunotherapy ◽

10.2217/imt.09.5 ◽

2009 ◽

Vol 1 (3) ◽

pp. 347-354 ◽

Cited By ~ 7

Author(s):

Alba Ruiz ◽

Meritxell Nomdedeu ◽

Marisa Ortega ◽

Merylene Lejeune ◽

Javier Setoain ◽

...

Keyword(s):

Dendritic Cells ◽

Therapeutic Vaccine ◽

Hiv 1

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Dendritic Cells Reveal a Broad Range of MHC Class I Epitopes for HIV-1 in Persons with Suppressed Viral Load on Antiretroviral Therapy

PLoS ONE ◽

10.1371/journal.pone.0012936 ◽

2010 ◽

Vol 5 (9) ◽

pp. e12936 ◽

Cited By ~ 10

Author(s):

Xiao-Li Huang ◽

Zheng Fan ◽

LuAnn Borowski ◽

Robbie B. Mailliard ◽

Morgane Rolland ◽

...

Keyword(s):

Dendritic Cells ◽

Viral Load ◽

Antiretroviral Therapy ◽

Mhc Class I ◽

Class I ◽

Hiv 1

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Phylogenetic analysis of HIV-1 archived DNA in blood and gut-associated lymphoid tissue in two patients under antiretroviral therapy

Gut Pathogens ◽

10.1186/s13099-021-00416-6 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Patricia Recordon-Pinson ◽

Annie Gosselin ◽

Petronela Ancuta ◽

Jean-Pierre Routy ◽

Hervé Fleury

Keyword(s):

Antiretroviral Therapy ◽

Genome Sequencing ◽

Dna Sequences ◽

Lymphoid Tissue ◽

Mononuclear Cells ◽

Therapeutic Vaccine ◽

Sequencing Analysis ◽

Proviral Dna ◽

Single Genome ◽

Hiv 1

AbstractOne of the approaches to cure human immunodeficiency virus (HIV) is the use of therapeutic vaccination. We have launched the Provir/Latitude 45 study to identify conserved CTL epitopes in archived HIV-1 DNA according to the HLA class I alleles in aviremic patients under antiretroviral therapy (ART). A HIV-1 polypeptidic therapeutic vaccine based on viral sequence data obtained from circulating blood was proposed; here, our aim was to compare the proviral DNA in blood and gut-associated lymphoid tissue (GALT). Peripheral blood mononuclear cells and gut biopsies were obtained from two HIV-1 infected patients under successful antiretroviral therapy. Total DNA was extracted including the proviral DNA. The HIV-1 reverse transcriptase was sequenced in both compartments using next generation sequencing followed by single genome sequencing; phylogenetic trees were established and compared. The proviral sequences of both compartments intra-patient exhibited a very low genetic divergence while it was possible to differentiate the sequences inter-patients; single genome sequencing analysis of two couples of samples confirmed that there was no compartmentalization of the sequences intra-patient. We conclude that, considering these two cases, the proviral DNA sequences in blood and GALT are similar and that the epitope analysis of HIV-1 provirus in blood should be considered as relevant to that observed in the GALT, a hard-to-reach major compartment, and can therefore be used for therapeutic vaccine approaches.

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

Pharmaceutics ◽

10.3390/pharmaceutics12070656 ◽

2020 ◽

Vol 12 (7) ◽

pp. 656 ◽

Cited By ~ 2

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.

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Persistent Abnormalities in Peripheral Blood Dendritic Cells and Monocytes from HIV-1-Positive Patients After 1 Year of Antiretroviral Therapy

JAIDS Journal of Acquired Immune Deficiency Syndromes ◽

10.1097/01.qai.0000209896.82255.d3 ◽

2006 ◽

Vol 41 (4) ◽

pp. 405-415 ◽

Cited By ~ 24

Author(s):

Maria Almeida ◽

Miguel Cordero ◽

Julia Almeida ◽

Alberto Orfao

Keyword(s):

Dendritic Cells ◽

Antiretroviral Therapy ◽

Peripheral Blood ◽

Hiv 1

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MODELING MONOCYTE-DERIVED DENDRITIC CELLS AS A THERAPEUTIC VACCINE AGAINST HIV

Journal of Biological System ◽

10.1142/s0218339018500262 ◽

2018 ◽

Vol 26 (04) ◽

pp. 579-601 ◽

Cited By ~ 2

Author(s):

SHUBHANKAR SAHA ◽

PRITI KUMAR ROY ◽

ROBERT SMITH?

Keyword(s):

Dendritic Cells ◽

T Lymphocytes ◽

Specific Antigen ◽

Therapeutic Vaccine ◽

Type I ◽

Viral Control ◽

Cross Presentation ◽

Infected Cells ◽

Immunologic Control ◽

Hiv 1

Successful immunologic control of HIV infection can be achieved in long-term non-progressors or HIV-1 controllers. Dendritic cells (DCs) are required for specific antigen presentation to naïve T lymphocytes and for antiviral, type I interferon secretion. To understand this mechanism, we develop a mathematical model that describes the role of direct presentation (replicating virus-infected DCs or other [Formula: see text] T cells directly) and cross presentation (DCs obtain antigen processed in other infected cells such as [Formula: see text] T lymphocytes) during HIV-1 infection. We find equilibria and determine stability in the case of no vaccination, and then, when vaccination is taken, we determine analytical thresholds for the strength and frequency of the vaccine to ensure the disease-free equilibrium remains stable. Our theoretical results suggest that the restoration of DC numbers may be predictive of immune restoration and may be a goal for immunotherapy to enhance viral control in a larger proportion of patients.

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