Loading dendritic cells with PLA-p24 nanoparticles or MVA expressing HIV genes induces HIV-1-specific T cell responses

Vaccine ◽  
2014 ◽  
Vol 32 (47) ◽  
pp. 6266-6276 ◽  
Author(s):  
Núria Climent ◽  
Séverine Munier ◽  
Núria Piqué ◽  
Felipe García ◽  
Vincent Pavot ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
T Cell Responses ◽  
Cell Responses ◽  
Hiv 1

scholarly journals Mature Dendritic Cells Infected with Canarypox Virus Elicit Strong Anti-Human Immunodeficiency Virus CD8+and CD4+ T-Cell Responses from Chronically Infected Individuals

2001 ◽  
Vol 75 (5) ◽  
pp. 2142-2153 ◽  
Author(s):  
Jose Engelmayer ◽  
Marie Larsson ◽  
Andrew Lee ◽  
Marina Lee ◽  
William I. Cox ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Dendritic Cells ◽  
T Cell ◽  
T Cell Responses ◽  
Virus Vectors ◽  
Cell Responses ◽  
Immunodeficiency Virus ◽  
Ifn Γ ◽  
Hiv 1 ◽  
Canarypox Virus

ABSTRACT Recombinant canarypox virus vectors containing human immunodeficiency virus type 1 (HIV-1) sequences are promising vaccine candidates, as they replicate poorly in human cells. However, when delivered intramuscularly the vaccines have induced inconsistent and in some cases transient antigen-specific cytotoxic T-cell (CTL) responses in seronegative volunteers. An attractive way to enhance these responses would be to target canarypox virus to professional antigen-presenting cells such as dendritic cells (DCs). We studied (i) the interaction between canarypox virus and DCs and (ii) the T-cell responses induced by DCs infected with canarypox virus vectors containing HIV-1 genes. Mature and not immature DCs resisted the cytopathic effects of canarypox virus and elicited strong effector CD8+ T-cell responses from chronically infected HIV+ individuals, e.g., cytolysis, and secretion of gamma interferon (IFN-γ) and β-chemokines. Furthermore, canarypox virus-infected DCs were >30-fold more efficient than monocytes and induced responses that were comparable to those induced by vaccinia virus vectors or peptides. Addition of exogenous cytokines was not necessary to elicit CD8+ effector cells, although the presence of CD4+ T cells was required for their expansion and maintenance. Most strikingly, canarypox virus-infected DCs were directly able to stimulate HIV-specific, IFN-γ-secreting CD4 helper responses from bulk as well as purified CD4+ T cells. Therefore, these results suggest that targeting canarypox virus vectors to mature DCs could potentially elicit both anti-HIV CD8+and CD4+ helper responses in vivo.

Induction of Potentially Protective HIV-Specific T-Cell Responses In Vitro by Gag mRNA-Electroporated Dendritic Cells.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1261-1261
Author(s):  
Zwi N. Berneman ◽  
Ellen R. Van Gulck ◽  
Leo Heyndrickx ◽  
Peter Ponsaerts ◽  
Viggo F.I. Van Tendeloo ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Cell Count ◽  
Cd8 T Cells ◽  
Peripheral Blood ◽  
T Cell Responses ◽  
Ifn Gamma ◽  
Cell Responses ◽  
Hiv 1

Abstract Human immunodeficiency virus type 1 (HIV-1) infection is characterized by dysfunction of HIV-1-specific T-lymphocytes. In order to suppress the virus and delay evolution to AIDS, antigen-loaded antigen-presenting cells, including dendritic cells (DC) might be useful to boost and broaden HIV-1-specific T-cell responses. Monocyte-derived DC from 15 untreated (“naive”) and 15 highly active anti-retroviral therapy (HAART)-treated HIV-1-infected patients were electroporated with codon-optimized (“humanized”) mRNA encoding consensus HxB-2 (hHxB-2) Gag protein. These DC were co-cultured for 1 week with autologous peripheral blood leucocytes (PBL). Potential expansion of specific T-cells was measured by comparing ELISPOT responses of PBL before and after co-culture, using a pool of overlapping peptides, spanning the HxB-2 Gag. Expansion of specific PBL after co-culture was noted for T cells producing interferon (IFN)-gamma, interleukin (IL)-2 and perforin (Wilcoxon signed rank test p<0.05, except for IL-2 in naive patients). From all HIV-1-seropositive persons tested, 12 HAART-treated and 12 naive patients match in absolute number of CD4+ T-cells. A comparison of the increase of the response between day 0 and after 1 week of stimulation between those two groups showed that the response was higher in HAART-treated subjects for IFN-gamma and IL-2 but not for perforin in comparison to untreated subjects. Examining purified CD4+ and CD8+ T-cells after co-culture revealed that HxB-2 Gag peptides induced IFN-gamma in both subsets, that IL-2 was only secreted by CD4+ T-cells and that perforin was dominantly secreted by CD8+ T-cells. Remarkably, the perforin response in the treatment-naive persons was negatively correlated with the peripheral blood absolute CD4+ and CD8+ T-cell count (respectively R=0.618, p=0.014; and R=0.529, p=0.043). Furthermore, the nadir absolute CD4+ T-cell count in HAART-treated subjects was positively correlated with the IL-2 response (R=0.521, p=0.046) and negatively correlated with the perforin response (R=0.588, p=0.021). In conclusion, DC from HAART-treated and therapy-naive subjects, electroporated with hHxB-2 gag mRNA have the capacity to induce secondary T-cell responses. In an earlier study (Van Gulck ER et al. Blood2006;107:1818–1827), we already demonstrated ex vivo that CD4+ and CD8+ T-cells from non-treated HIV-1-infected subjects can be directly triggered by DC electroporated with autologous proviral-derived gag mRNA. Taken together, our results open the perspective for a DC immunotherapy for HIV disease.

scholarly journals Dendritic Cells Exposed to MVA-Based HIV-1 Vaccine Induce Highly Functional HIV-1-Specific CD8+ T Cell Responses in HIV-1-Infected Individuals

PLoS ONE ◽  
2011 ◽  
Vol 6 (5) ◽  
pp. e19644 ◽  
Author(s):  
Núria Climent ◽  
Susana Guerra ◽  
Felipe García ◽  
Cristina Rovira ◽  
Laia Miralles ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Cell Responses ◽  
Hiv 1

scholarly journals Interleukin-12p70 Expression by Dendritic Cells of HIV-1-Infected Patients Fails to Stimulategag-Specific Immune Responses

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Ellen Van Gulck ◽  
Nathalie Cools ◽  
Derek Atkinson ◽  
Lotte Bracke ◽  
Katleen Vereecken ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Immune Responses ◽  
T Cell Responses ◽  
Hiv Replication ◽  
Cell Responses ◽  
Antigen Presenting ◽  
Hiv 1 ◽  
Unique Capability

A variety of immune-based therapies has been developed in order to boost or induce protective CD8+T cell responses in order to control HIV replication. Since dendritic cells (DCs) are professional antigen-presenting cells (APCs) with the unique capability to stimulate naïve T cells into effector T cells, their use for the induction of HIV-specific immune responses has been studied intensively. In the present study we investigated whether modulation of the activation state of DCs electroporated with consensus codon-optimized HxB2gagmRNA enhances their capacity to induce HIVgag-specific T cell responses. To this end, mature DCs were (i) co-electroporated with mRNA encoding interleukin (IL)-12p70 mRNA, or (ii) activated with a cytokine cocktail consisting of R848 and interferon (IFN)-γ. Our results confirm the ability of HxB2gag-expressing DCs to expand functional HIV-specific CD8+T cells. However, although most of the patients had detectablegag-specific CD8+T cell responses, no significant differences in the level of expansion of functional CD8+T cells could be demonstrated when comparing conventional or immune-modulated DCs expressing IL-12p70. This result which goes against expectation may lead to a re-evaluation of the need for IL-12 expression by DCs in order to improve T-cell responses in HIV-1-infected individuals.

scholarly journals Toll-Like Receptor Ligands Modulate Dendritic Cells to Augment Cytomegalovirus- and HIV-1-Specific T Cell Responses

2003 ◽  
Vol 171 (8) ◽  
pp. 4320-4328 ◽  
Author(s):  
Karin Loré ◽  
Michael R. Betts ◽  
Jason M. Brenchley ◽  
Janaki Kuruppu ◽  
Soorena Khojasteh ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
T Cell Responses ◽  
Toll Like Receptor ◽  
Receptor Ligands ◽  
Cell Responses ◽  
Hiv 1

Co-delivery of Antigen p24 and NOD-ligands by PLA Nanoparticles to Human Dendritic Cells Promote Highly Functional HIV-1-Specific T-cell Responses

2014 ◽  
Vol 30 (S1) ◽  
pp. A240-A241 ◽  
Author(s):  
Núria Climent ◽  
Vincent Pavot ◽  
Felipe García ◽  
Thierry Lioux ◽  
Eric Perouzel ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
T Cell Responses ◽  
Cell Responses ◽  
Human Dendritic Cells ◽  
Hiv 1

Functional T-cell responses generated by dendritic cells expressing the early HIV-1 proteins Tat, Rev and Nef

Vaccine ◽  
2008 ◽  
Vol 26 (29-30) ◽  
pp. 3735-3741 ◽  
Author(s):  
Sabine D. Allard ◽  
Katrien Pletinckx ◽  
Karine Breckpot ◽  
Carlo Heirman ◽  
Aude Bonehill ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
T Cell Responses ◽  
Cell Responses ◽  
Hiv 1

scholarly journals Native HIV-1 Tat Protein Targets Monocyte-Derived Dendritic Cells and Enhances Their Maturation, Function, and Antigen-Specific T Cell Responses

2002 ◽  
Vol 168 (1) ◽  
pp. 197-206 ◽  
Author(s):  
Emanuele Fanales-Belasio ◽  
Sonia Moretti ◽  
Filomena Nappi ◽  
Giovanni Barillari ◽  
Fabiola Micheletti ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
T Cell Responses ◽  
Tat Protein ◽  
Protein Targets ◽  
Cell Responses ◽  
Hiv 1 ◽  
Maturation Function

scholarly journals Primary Human Immunodeficiency Virus Type 1-Specific CD8+ T-Cell Responses Induced by Myeloid Dendritic Cells

2009 ◽  
Vol 83 (12) ◽  
pp. 6288-6299 ◽  
Author(s):  
Bonnie A. Colleton ◽  
Xiao-Li Huang ◽  
Nada M. Melhem ◽  
Zheng Fan ◽  
Luann Borowski ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Dendritic Cells ◽  
T Cell ◽  
T Cell Responses ◽  
Myeloid Dendritic Cells ◽  
Cell Responses ◽  
Immunodeficiency Virus ◽  
Ifn Γ ◽  
Hiv 1

ABSTRACT Induction of an antigenically broad and vigorous primary T-cell immune response by myeloid dendritic cells (DC) in blood and tissues could be important for an effective prophylactic or therapeutic vaccine to human immunodeficiency virus type 1 (HIV-1). Here we show that a primary CD8+ T-cell response can be induced by HIV-1 peptide-loaded DC derived from blood monocytes of HIV-1-negative adults and neonates (moDC) and by Langerhans cells (LC) and interstitial, dermal-intestinal DC (idDC) derived from CD34+ stem cells of neonatal cord blood. Optimal priming of single-cell gamma interferon (IFN-γ) production by CD8+ T cells required CD4+ T cells and was broadly directed to multiple regions of Gag, Env, and Nef that corresponded to known and predicted major histocompatibility complex class I epitopes. Polyfunctional CD8+ T-cell responses, defined as single-cell production of more than one cytokine (IFN-γ, interleukin 2, or tumor necrosis factor alpha), chemokine (macrophage inhibitory factor 1β), or cytotoxic degranulation marker CD107a, were primed by moDC, LC, and idDC to HIV-1 Gag and reverse transcriptase epitopes, as well as to Epstein-Barr virus and influenza A virus epitopes. Thus, three major types of blood and tissue myeloid DC targeted by HIV-1, i.e., moDC, LC, and idDC, can prime multispecific, polyfunctional CD8+ T-cell responses to HIV-1 and other viral antigens.

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