Faculty Opinions recommendation of Dendritic cell-based vaccine strategy against human immunodeficiency virus clade C: skewing the immune response toward a helper T cell type 2 profile.

2007 ◽  
Author(s):  
Luigi Buonaguro
Keyword(s):  
Immune Response ◽  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Dendritic Cell ◽  
Cell Type ◽  
Vaccine Strategy ◽  
Immunodeficiency Virus ◽  
Clade C ◽  
Dendritic Cell Based Vaccine

Dendritic Cell-Based Vaccine Strategy against Human Immunodeficiency Virus Clade C: Skewing The Immune Response Toward A Helper T Cell Type 2 Profile

2007 ◽  
Vol 20 (1) ◽  
pp. 160-169 ◽  
Author(s):  
Andreas Gruber ◽  
Alistair S. Chalmers ◽  
Robert A. Rasmussen ◽  
Helena Ong ◽  
Sergei Popov ◽  
...  
Keyword(s):  
Immune Response ◽  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Dendritic Cell ◽  
Cell Type ◽  
Vaccine Strategy ◽  
Immunodeficiency Virus ◽  
Clade C ◽  
Dendritic Cell Based Vaccine

scholarly journals Production of a Dendritic Cell-Based Vaccine Containing Inactivated Autologous Virus for Therapy of Patients with Chronic Human Immunodeficiency Virus Type 1 Infection

2008 ◽  
Vol 16 (2) ◽  
pp. 233-240 ◽  
Author(s):  
Theresa L. Whiteside ◽  
Paolo Piazza ◽  
Amanda Reiter ◽  
Joanna Stanson ◽  
Nancy C. Connolly ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Human Immunodeficiency Virus ◽  
T Cells ◽  
T Cell ◽  
Dendritic Cell ◽  
Human Immunodeficiency Virus Type ◽  
Endogenous Virus ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT In preparation for a pilot clinical trial in patients with chronic human immunodeficiency virus type 1 (HIV-1) infection, a novel dendritic cell (DC)-based vaccine is being manufactured. The trial will test the hypothesis that isolated endogenous virus presented by DCs serves as a potent immunogen for activation of CD8+ and CD4+ T cells specific for a broad range of autologous HIV-1 antigens. Production of the vaccine under good manufacture practice conditions involves (i) autologous virus isolation; (ii) superinfection of CD4+ T cells with the virus; (iii) inactivation of the virus in CD4+ T cells, T-cell apoptosis, and coincubation of T cells with autologous DCs; and (iv) product testing and release. Endogenous virus was isolated from peripheral blood-derived CD4+ T cells of three HIV-1-positive subjects by coincubation with autologous OKT-3-stimulated CD4+ T cells. CD4+ T-cell supernatants were tested for p24 levels by enzyme-linked immunosorbent assay (>25 ng/ml) and for the 50% tissue culture infective doses (TCID50; which ranged from 4,642 to 46,416/ml on day 19 of culture). Autologous CD4+ T cells that were separated on immunobeads (>95% purity) and superinfected with virus-expressed p24 (28 to 54%) had TCID50 of >400/ml on days 5 to 10. Virus inactivation with psoralen (20 μg/ml) and UVB irradiation (312 nm) reduced the TCID50 of the supernatants from 199,986 to 11/ml (>99%). 7-Amino-actinomycin D-positive, annexin V-positive CD4+ T cells were fed to autologous DCs generated by using the Elutra cell separation system and the Aastrom system. Flow analysis showed that DC loading was complete in 24 h. On the basis of these translational results and experience with the generation of DCs from HIV-1-infected patients in a previous clinical trial, the Investigational New Drug application for clinical vaccination was submitted and approved by the FDA (application no. BB-IND-13137).

scholarly journals Enhanced Breadth of CD4 T-Cell Immunity by DNA Prime and Adenovirus Boost Immunization to Human Immunodeficiency Virus Env and Gag Immunogens

2005 ◽  
Vol 79 (13) ◽  
pp. 8024-8031 ◽  
Author(s):  
Lan Wu ◽  
Wing-pui Kong ◽  
Gary J. Nabel
Keyword(s):  
Immune Response ◽  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Cell Epitope ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Cell Immunity ◽  
Immunodeficiency Virus ◽  
Boost Immunization ◽  
Cellular And Humoral Immunity

ABSTRACT A variety of gene-based vaccination approaches have been used to enhance the immune response to viral pathogens. Among them, the ability to perform heterologous immunization by priming with DNA and boosting with replication-defective adenoviral (ADV) vectors encoding foreign antigens has proven particularly effective in eliciting enhanced cellular and humoral immunity compared to either agent alone. Because adenoviral vector immunization alone can elicit substantial cellular and humoral immune responses in a shorter period of time, we asked whether the immune response induced by the prime-boost immunization was different from adenoviral vaccines with respect to the potency and breadth of T-cell recognition. While DNA/ADV immunization stimulated the CD8 response, it was directed to the same epitopes in Gag and Env immunogens of human immunodeficiency virus as DNA or ADV alone. In contrast, the CD4 response to these immunogens diversified after DNA/ADV immunization compared to each vector alone. These findings suggest that the diversity of the CD4 immune response is increased by DNA/ADV prime-boost vaccination and that these components work synergistically to enhance T-cell epitope recognition.

scholarly journals Long-Term Specific Immune Responses Induced in Humans by a Human Immunodeficiency Virus Type 1 Lipopeptide Vaccine: Characterization of CD8+-T-Cell Epitopes Recognized

2003 ◽  
Vol 77 (20) ◽  
pp. 11220-11231 ◽  
Author(s):  
Hanne Gahéry-Ségard ◽  
Gilles Pialoux ◽  
Suzanne Figueiredo ◽  
Céline Igéa ◽  
Mathieu Surenaud ◽  
...  
Keyword(s):  
Immune Response ◽  
Human Immunodeficiency Virus ◽  
T Cell ◽  
T Cell Responses ◽  
T Cell Epitopes ◽  
Cell Responses ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT We studied the effect of booster injections and the long-term immune response after injections of an anti-human immunodeficiency virus type 1 (HIV-1) lipopeptide vaccine. This vaccine was injected alone or with QS21 adjuvant to 28 HIV-uninfected volunteers. One month later, after a fourth injection of the vaccine, B- and T-cell anti-HIV responses were detected in >85% of the vaccinated volunteers. One year after this injection, a long-term immune response was observed in >50% of the volunteers. At this point, a positive QS21 effect was observed only in the sustained B-cell and CD4+-T-cell responses. To better characterize the CD8+-T-cell response, we used a gamma interferon enzyme-linked immunospot method and a bank of 59 HIV-1 epitopes. For the six most common HLA molecules (HLA-A2, -A3, -A11, -A24, -B7 superfamily, and -B8), an average of 10 (range, 3 to 15) HIV-1 epitopes were tested. CD8+-T-cell responses were evaluated according to the HLA class I molecules of the volunteers. Each assessment was based on 18 HIV-1 epitopes in average. We showed that 31 HIV-1 epitopes elicited specific CD8+-T-cell responses after vaccination. The most frequently recognized peptides were Nef 68-76 (-B7), Nef 71-79 (-B7), Nef 84-92 (-A11), Nef 135-143 (-B7), Nef 136-145 (-A2), Nef 137-145 (-A2), Gag 259-267 (-B8), Gag 260-268 (-A2), Gag 267-274 (-A2), Gag 267-277 (-B7), and Gag 276-283 (A24). We found that CD8+-T-cell epitopes were induced at a higher number after a fourth injection (P < 0.05 compared to three injections), which indicates an increase in the breadth of HIV CD8+-T-cell epitope recognition after the boost.

Superinfection with Human Immunodeficiency Virus Type 2 Can Reactivate Virus Production in Baboons but Is Contained by a CD8 T Cell Antiviral Response

1997 ◽  
Vol 176 (4) ◽  
pp. 948-959 ◽  
Author(s):  
Christopher P. Locher ◽  
David J. Blackbourn ◽  
Susan W. Barnett ◽  
Krishna K. Murthy ◽  
Elizabeth K. Cobb ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Virus Production ◽  
Cd8 T Cell ◽  
Antiviral Response ◽  
Immunodeficiency Virus

scholarly journals Coinfection with Schistosoma mansoni Reactivates Viremia in Rhesus Macaques with Chronic Simian-Human Immunodeficiency Virus Clade C Infection

2007 ◽  
Vol 75 (4) ◽  
pp. 1751-1756 ◽  
Author(s):  
Mila Ayash-Rashkovsky ◽  
Agnès-Laurence Chenine ◽  
Lisa N. Steele ◽  
Sandra J. Lee ◽  
Ruijiang Song ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Viral Replication ◽  
Schistosoma Mansoni ◽  
Rhesus Macaques ◽  
Cell Subset ◽  
Interleukin 4 ◽  
Immunodeficiency Virus ◽  
Clade C

ABSTRACT We tested the hypothesis that helminth parasite coinfection would intensify viremia and accelerate disease progression in monkeys chronically infected with an R5 simian-human immunodeficiency virus (SHIV) encoding a human immunodeficiency virus type 1 (HIV-1) clade C envelope. Fifteen rhesus monkeys with stable SHIV-1157ip infection were enrolled into a prospective, randomized trial. These seropositive animals had undetectable viral RNA and no signs of immunodeficiency. Seven animals served as virus-only controls; eight animals were exposed to Schistosoma mansoni cercariae. From week 5 after parasite exposure onward, coinfected animals shed eggs in their feces, developed eosinophilia, and had significantly higher mRNA expression of the T-helper type 2 cytokine interleukin-4 (P = 0.001) than animals without schistosomiasis. Compared to virus-only controls, viral replication was significantly increased in coinfected monkeys (P = 0.012), and the percentage of their CD4+ CD29+ memory cells decreased over time (P = 0.05). Thus, S. mansoni coinfection significantly increased viral replication and induced T-cell subset alterations in monkeys with chronic SHIV clade C infection.

scholarly journals Higher Homologous and Lower Cross-Reactive Gag-Specific T-Cell Responses in Human Immunodeficiency Virus Type 2 (HIV-2) Than in HIV-1 Infection

2008 ◽  
Vol 82 (17) ◽  
pp. 8619-8628 ◽  
Author(s):  
Wim Jennes ◽  
Makhtar Camara ◽  
Tandakha Dièye ◽  
Souleymane Mboup ◽  
Luc Kestens
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
T Cell Responses ◽  
Cell Responses ◽  
Cell Counts ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Human immunodeficiency virus type 2 (HIV-2) infection results in slower CD4+ T-cell decline, lower plasma viral load levels, and hence slower progression of the disease than does HIV-1 infection. Although the reasons for this are not clear, it is possible that HIV-2 replication is more effectively controlled by host responses. We used aligned pools of overlapping HIV-1 and HIV-2 Gag peptides in an enhanced gamma interferon enzyme-linked immunospot assay to compare the levels of homologous and cross-reactive Gag-specific T-cell responses between HIV-1- and HIV-2-infected patients. HIV-2-infected patients showed broader and stronger homologous Gag-specific T-cell responses than HIV-1-infected patients. In contrast, the cross-reactive T-cell responses in HIV-2-infected patients were both narrower and weaker than those in HIV-1-infected patients, in line with overall weaker correlations between homologous and heterologous T-cell responses among HIV-2-infected patients than among HIV-1-infected patients. Cross-reactive responses in HIV-2-infected patients tended to correlate directly with HIV-1/HIV-2 Gag sequence similarities; this was not found in HIV-1-infected patients. The CD4+ T-cell counts of HIV-2-infected patients correlated directly with homologous responses and inversely with cross-reactive responses; this was not found in HIV-1-infected patients. Our data support a model whereby high-level HIV-2-specific T-cell responses control the replication of HIV-2, thus limiting viral diversification and priming of HIV-1 cross-reactive T-cell responses over time. However, we cannot exclude the possibility that HIV-2 replication is controlled by other host factors and that HIV-2-specific T-cell responses are better maintained in the context of slow viral divergence and a less damaged immune system. Understanding the nature of immune control of HIV-2 infection could be crucial for HIV vaccine design.

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