Dendritic-Cell Specific Antigen Hiv-1: Novel Terapi Berbasis Biomolekuler sebagai Imunomodulator pada Penderita HIV Tipe 1

Infeksi Human Immunodeficiency Virus (HIV), baik tipe 1 yang tersebar ke seluruh dunia maupun tipe 2 yang terisolasi di Afrika, masih menjadi tantangan di bidang kesehatan dunia termasuk Indonesia. Angka HIV yang tinggi ini penting untuk ditangani karena bahaya komplikasi yang mengintai. Penatalaksanaan dan terapi HIV yang ada saat ini dengan penggunaan antiretroviral memiliki keterbatasan dilihat dari efek terapi dan efek samping yang ditimbulkan. Pengembangan dan penemuan modalitas terapi yang memiliki potensi efek terapi yang lebih optimal merupakan suatu tantangan yang terus diupayakan dalam penanganan HIV ini. Salah satunya adalah pengembangan imunoterapi berbasis sel dendritik. Literature review ini ditulis secara sistematis mengenai laporan studi terkait hal di atas dari berbagai sumber termasuk Google Scholar, PubMed, Research Gate untuk menguraikan potensi sel dendritik sebagai imunomodulator pada penderita HIV-1. Modalitas imunoterapi ini dikonstruksi dalam bentuk vaksin berbasis sel dendritik, sel yang berperan pada patogenesis HIV, yang diadministrasikan secara intradermal. Vaksin yang diberikan akan menstimulasi respon imun dan dapat digunakan tidak saja sebagai upaya terapi pada penderita tapi berpotensi digunakan sebagai pencegahan.

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

Clinical and Vaccine Immunology ◽

10.1128/cvi.00066-08 ◽

2008 ◽

Vol 16 (2) ◽

pp. 233-240 ◽

Cited By ~ 21

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).

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In Vitro Human Immunodeficiency Virus Eradication by Autologous CD8+ T Cells Expanded with Inactivated-Virus-Pulsed Dendritic Cells

Journal of Virology ◽

10.1128/jvi.75.19.8949-8956.2001 ◽

2001 ◽

Vol 75 (19) ◽

pp. 8949-8956 ◽

Cited By ~ 32

Author(s):

Wei Lu ◽

Jean-Marie Andrieu

Keyword(s):

Human Immunodeficiency Virus ◽

T Cells ◽

Dendritic Cells ◽

Mononuclear Cells ◽

Specific Antigen ◽

Lymphoid Tissues ◽

Immunodeficiency Virus ◽

Anti Hiv ◽

Hiv 1

ABSTRACT Despite significant immune recovery with potent highly active antiretroviral therapy (HAART), eradication of human immunodeficiency virus (HIV) from the bodies of infected individuals represents a challenge. We hypothesized that an inadequate or inappropriate signal in virus-specific antigen presentation might contribute to the persistent failure to mount efficient anti-HIV immunity in most HIV-infected individuals. Here, we conducted an in vitro study with untreated (n = 10) and HAART-treated (n = 20) HIV type 1 (HIV-1) patients which showed that pulsing of monocyte-derived dendritic cells (DC) with aldrithiol-2-inactivated autologous virus resulted in the expansion of virus-specific CD8+ T cells which were capable of killing HIV-1-infected cells and eradicating the virus from cultured patient peripheral blood mononuclear cells independently of the disease stages and HAART response statuses of the patients. This in vitro anti-HIV effect was further enhanced by the HIV protease inhibitor indinavir (at a nonantiviral concentration), which has been shown previously to be able to up-regulate directly patient T-cell proliferation following immune stimulation. However, following a 2-day treatment with culture supernatant derived from immune-activated T cells (which mimics an in vivo environment of HIV-disseminated and immune-activated lymphoid tissues), DC lost their capacity to present de novo inactivated-virus-derived antigens. These findings provide important information for understanding the establishment of chronic HIV infection and indicate a perspective for clinical use of DC-based therapeutic vaccines against HIV.

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CD8+-Cell Antiviral Factor Activity Is Not Restricted to Human Immunodeficiency Virus (HIV)-Specific T Cells and Can Block HIV Replication after Initiation of Reverse Transcription

Journal of Virology ◽

10.1128/jvi.74.10.4456-4464.2000 ◽

2000 ◽

Vol 74 (10) ◽

pp. 4456-4464 ◽

Cited By ~ 27

Author(s):

Sylvie Le Borgne ◽

Michèle Février ◽

Christian Callebaut ◽

Steven P. Lee ◽

Yves Rivière

Keyword(s):

Human Immunodeficiency Virus ◽

T Cells ◽

Reverse Transcription ◽

Acute Infection ◽

Specific Antigen ◽

Suppressive Activity ◽

Hiv Replication ◽

Immunodeficiency Virus ◽

Hiv 1

ABSTRACT CD8+ lymphocytes from human immunodeficiency virus (HIV)-infected patients can suppress in vitro HIV replication in CD4+ T cells by a noncytolytic mechanism involving secreted CD8+-cell antiviral factor(s) (CAF). Using an HIV Nef-specific cytotoxic-T-lymphocyte (CTL) line and autologous CD4+ T cells infected with a nef-deleted HIV-1 virus, we demonstrated that, after a priming antigenic stimulation, this suppression does not require the presence of the specific antigen during the effector phase. Furthermore, using an Epstein-Barr virus (EBV)-specific CTL line from an HIV-seronegative donor, we demonstrated that the ability to inhibit HIV replication in a noncytolytic manner is not restricted to HIV-specific effector cells; indeed, EBV-specific CTL were as efficient as HIV-specific effectors in suppressing R5 or X4 HIV-1 strain replication in vitro. This HIV-suppressive activity mediated by a soluble factor(s) present in the culture supernatant was detectable for up to 14 days following stimulation of EBV-specific CD8+ cells with the cognate epitope peptide. Following acute infection of CEM cells with an X4 strain of HIV-1, EBV-specific CTL line supernatant containing HIV-suppressive activity did not block virus entry but was shown to interfere with virus replication after the first template switching of reverse transcription. Our results suggest that the noncytolytic control of HIV replication by EBV-specific CD8+ T lymphocytes corresponded to a CAF-like activity and thus demonstrate that CAF production may not be restricted to CTL induced during HIV disease. Moreover, CAF acts after reverse transcription at least for X4 isolate replication inhibition.

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Sugar-Binding Proteins Potently Inhibit Dendritic Cell Human Immunodeficiency Virus Type 1 (HIV-1) Infection and Dendritic-Cell-Directed HIV-1 Transfer

Journal of Virology ◽

10.1128/jvi.79.21.13519-13527.2005 ◽

2005 ◽

Vol 79 (21) ◽

pp. 13519-13527 ◽

Cited By ~ 40

Author(s):

Stuart G. Turville ◽

Kurt Vermeire ◽

Jan Balzarini ◽

Dominique Schols

Keyword(s):

Human Immunodeficiency Virus ◽

Dendritic Cell ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Phase Transfer ◽

Second Phase ◽

Plant Lectins ◽

Immunodeficiency Virus ◽

Hiv 1

ABSTRACT Both endocytic uptake and viral fusion can lead to human immunodeficiency virus type 1 (HIV-1) transfer to CD4+ lymphocytes, either through directional regurgitation (infectious transfer in trans [I-IT]) or through de novo viral production in dendritic cells (DCs) resulting in a second-phase transfer to CD4+ lymphocytes (infectious second-phase transfer [I-SPT]). We have evaluated in immature monocyte-derived DCs both pathways of transfer with regard to their susceptibilities to being blocked by potential microbicidal compounds, including cyanovirin (CNV); the plant lectins Hippeastrum hybrid agglutinin, Galanthus nivalis agglutinin, Urtica dioica agglutinin, and Cymbidium hybrid agglutinin; and the glycan mannan. I-IT was a relatively inefficient means of viral transfer compared to I-SPT at both high and low levels of the viral inoculum. CNV was able to completely block I-IT at 15 μg/ml. All other compounds except mannan could inhibit I-IT by at least 90% when used at doses of 15 μg/ml. In contrast, efficient inhibition of I-SPT was remarkably harder to achieve, as 50% effective concentration levels for plant lectins and CNV to suppress this mode of HIV-1 transfer increased significantly. Thus, our findings indicate that I-SPT may be more elusive to targeting by antiviral drugs and stress the need for drugs affecting the pronounced inhibition of the infection of DCs by HIV-1.

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Dendritic Cell-Mediated Viral Transfer to T Cells Is Required for Human Immunodeficiency Virus Type 1 Persistence in the Face of Rapid Cell Turnover

Journal of Virology ◽

10.1128/jvi.76.21.10692-10701.2002 ◽

2002 ◽

Vol 76 (21) ◽

pp. 10692-10701 ◽

Cited By ~ 50

Author(s):

Suryaram Gummuluru ◽

Vineet N. KewalRamani ◽

Michael Emerman

Keyword(s):

Human Immunodeficiency Virus ◽

T Cells ◽

Dendritic Cell ◽

Virus Replication ◽

Adhesion Molecule ◽

Cell Turnover ◽

Immunodeficiency Virus ◽

Hiv 1

ABSTRACT Human immunodeficiency virus type 1 (HIV-1)-infected and activated CD4+ T cells have short half-lives in vivo (<2 days). We have established an in vitro culture system in which infected T cells are turned over frequently to provide a model system that examines this important facet of in vivo HIV-1 replication. We observed that virus replication in T cells under rapid-turnover conditions was possible only when immature dendritic cells or DC-SIGN-expressing cells mediated HIV-1 transmission to T cells. Virus replication was initiated more rapidly in T cells infected with the cell-associated form of virus compared to infection by the cell-free route. This accelerated transfer of virus required adhesion molecule-mediated interactions between the virus-presenting cell and T cell, but surprisingly, HIV-1 transfer could occur independently of DC-SIGN (DC-specific intracellular adhesion molecule 3 [ICAM-3]-grabbing nonintegrin)in the dendritic-cell-T-cell cocultures. These results suggest that dendritic cell-mediated transmission of HIV-1 enables virus replication under conditions of rapid cell turnover in vivo.

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Prevalence of Human Immunodeficiency Virus and Malaria Co-Infection in Nigeria: A Review of Published Literature

Global Journal of Health Science ◽

10.5539/gjhs.v12n1p30 ◽

2019 ◽

Vol 12 (1) ◽

pp. 30

Author(s):

Omotayo S. Alaofin ◽

Kantharuben Naidoo

Keyword(s):

Human Immunodeficiency Virus ◽

Literature Review ◽

Low Income ◽

Highly Active Antiretroviral Therapy ◽

Management Practice ◽

Epidemiological Data ◽

Google Scholar ◽

Low Income Countries ◽

Infection Prevalence ◽

Immunodeficiency Virus

Background: Human immunodeficiency virus and malaria are significant global health challenges. Both diseases contribute to the global burden of disease and poverty notable amongst low-income countries, including sub-Sahara Africa and Nigeria. There are little or no available review articles on the prevailing epidemiological data on human immunodeficiency virus and malaria interaction in Nigeria. Aim: This literature review aims to update knowledge on human immunodeficiency virus and malaria co-infection and determine the prevalence of human immunodeficiency virus and malaria from published literature. Method: This work reviewed published articles on human immunodeficiency virus/malaria co-infection published in English in PubMed, Google Scholar, and ScienceDirect. An internet search on Google Scholar was also conducted for studies that were conducted between 2007 and 2017 in Nigeria. Result: The literature review indicated that the highest prevalence of human immunodeficiency virus and malaria co-infection in Nigeria is 86.2%. The mean ± SD among the HIV-malaria co-infected group and the negative malaria group in all of Nigeria’s geo-political zones are 36.6 ± 25.5 and 19.5 ± 15.3, respectively. The highest mean prevalence of 64.5% was reported in human immunodeficiency virus patients co-infected with malaria in the northwest zone. The use of highly active antiretroviral therapy is also associated with a reduced mean positive prevalence of 31.26%. Conclusion: Human immunodeficiency virus-positive individuals across all the geopolitical zones in Nigeria are at high risk of malaria. Findings from this review of literature will provide additional information on HIV-malaria co-infection prevalence and guide public health prevention, control and management practice.

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