scholarly journals Induction of Robust Immune Responses against Human Immunodeficiency Virus Is Supported by the Inherent Tropism of Adeno-Associated Virus Type 5 forDendritic Cells

2006 ◽  
Vol 80 (24) ◽  
pp. 11899-11910 ◽  
Author(s):  
Ke-Qin Xin ◽  
Hiroaki Mizukami ◽  
Masashi Urabe ◽  
Yoshihiko Toda ◽  
Kaori Shinoda ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Immune Responses ◽  
Virus Type ◽  
Antigen Presenting Cells ◽  
Hek293 Cells ◽  
Specific Cell ◽  
Adeno Associated Virus ◽  
Virus Serotype ◽  
Immunodeficiency Virus ◽  
Antigen Presenting

ABSTRACT The ability of adeno-associated virus serotype 1 to 8 (AAV1 to AAV8) vectors expressing the human immunodeficiency virus type 1 (HIV-1) Env gp160 (AAV-HIV) to induce an immune response was evaluated in BALB/c mice. The AAV5 vector showed a higher tropism for both mouse and human dendritic cells (DCs) than did the AAV2 vector, whereas other AAV serotype vectors transduced DCs only poorly. AAV1, AAV5, AAV7, and AAV8 were more highly expressed in muscle cells than AAV2. An immunogenicity study of AAV serotypes indicates that AAV1, AAV5, AAV7, and AAV8 vectors expressing the Env gp160 gene induced higher HIV-specific humoral and cell-mediated immune responses than the AAV2 vector did, with the AAV5 vector producing the best responses. Furthermore, mice injected with DCs that had been transduced ex vivo with an AAV5 vector expressing the gp160 gene elicited higher HIV-specific cell-mediated immune responses than did DCs transduced with AAV1 and AAV2 vectors. We also found that AAV vectors produced by HEK293 cells and insect cells elicit similar levels of antigen-specific immune responses. These results demonstrate that the immunogenicity of AAV vectors depends on their tropism for both antigen-presenting cells (such as DCs) and non-antigen-presenting cells (such as muscular cells) and that AAV5 is a better vector than other AAV serotypes. These results may aid in the development of AAV-based vaccine and gene therapy.

scholarly journals Recruitment of Antigen-Presenting Cells to the Site of Inoculation and Augmentation of Human Immunodeficiency Virus Type 1 DNA Vaccine Immunogenicity by In Vivo Electroporation

2008 ◽  
Vol 82 (11) ◽  
pp. 5643-5649 ◽  
Author(s):  
Jinyan Liu ◽  
Rune Kjeken ◽  
Iacob Mathiesen ◽  
Dan H. Barouch
Keyword(s):  
Human Immunodeficiency Virus ◽  
Dna Vaccine ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Antigen Presenting Cells ◽  
In Vivo Electroporation ◽  
Immunodeficiency Virus ◽  
Antigen Presenting

ABSTRACT In vivo electroporation (EP) has been shown to augment the immunogenicity of plasmid DNA vaccines, but its mechanism of action has not been fully characterized. In this study, we show that in vivo EP augmented cellular and humoral immune responses to a human immunodeficiency virus type 1 Env DNA vaccine in mice and allowed a 10-fold reduction in vaccine dose. This enhancement was durable for over 6 months, and re-exposure to antigen resulted in anamnestic effector and central memory CD8+ T-lymphocyte responses. Interestingly, in vivo EP also recruited large mixed cellular inflammatory infiltrates to the site of inoculation. These infiltrates contained 45-fold-increased numbers of macrophages and 77-fold-increased numbers of dendritic cells as well as 2- to 6-fold-increased numbers of B and T lymphocytes compared to infiltrates following DNA vaccination alone. These data suggest that recruiting inflammatory cells, including antigen-presenting cells (APCs), to the site of antigen production substantially improves the immunogenicity of DNA vaccines. Combining in vivo EP with plasmid chemokine adjuvants that similarly recruited APCs to the injection site, however, did not result in synergy.

scholarly journals Activation by Inflammatory Stimuli Increases Neutrophil Binding of Human Immunodeficiency Virus Type 1 and Subsequent Infection of Lymphocytes

2004 ◽  
Vol 78 (19) ◽  
pp. 10833-10836 ◽  
Author(s):  
Ali M. Gabali ◽  
Joshua J. Anzinger ◽  
Gregory T. Spear ◽  
Larry L. Thomas
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Incubation Temperature ◽  
Hek293 Cells ◽  
Increased Risk ◽  
Immunodeficiency Virus ◽  
Inflammatory Stimuli ◽  
Hiv 1

ABSTRACT Resting neutrophils bind human immunodeficiency virus type 1 (HIV-1) and efficiently transfer infection to lymphocytes. The present study shows that a brief activation by inflammatory stimuli increases the neutrophil binding levels of both R5 and X4 isolates of HIV-1 at least twofold. The binding occurs independently of CD4, gp120, and incubation temperature and is observed with HIV-1 propagated either in lymphocytes or in HEK293 cells. Significantly, HIV-1 bound to the activated neutrophils accelerates the infection of activated lymphocytes compared to free HIV-1 or to HIV-1 bound to resting neutrophils. It is proposed that these events may contribute to the increased risk of HIV-1 transmission at sites of mucosal infection.

scholarly journals Induction of Humoral Immune Responses following Vaccination with Envelope-Containing, Formaldehyde-Treated, Thermally Inactivated Human Immunodeficiency Virus Type 1

2005 ◽  
Vol 79 (8) ◽  
pp. 4927-4935 ◽  
Author(s):  
B. Poon ◽  
J. T. Safrit ◽  
H. McClure ◽  
C. Kitchen ◽  
J. F. Hsu ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Thermal Treatment ◽  
Immune Responses ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT The lack of success of subunit human immunodeficiency virus type 1 (HIV-1) vaccines to date suggests that multiple components or a complex virion structure may be required. We previously demonstrated retention of the major conformational epitopes of HIV-1 envelope following thermal treatment of virions. Moreover, antibody binding to some of these epitopes was significantly enhanced following thermal treatment. These included the neutralizing epitopes identified by monoclonal antibodies 1b12, 2G12, and 17b, some of which have been postulated to be partially occluded or cryptic in native virions. Based upon this finding, we hypothesized that a killed HIV vaccine could be derived to elicit protective humoral immune responses. Shedding of HIV-1 envelope has been described for some strains of HIV-1 and has been cited as one of the major impediments to developing an inactivated HIV-1 vaccine. In the present study, we demonstrate that treatment of virions with low-dose formaldehyde prior to thermal inactivation retains the association of viral envelope with virions. Moreover, mice and nonhuman primates vaccinated with formaldehyde-treated, thermally inactivated virions produce antibodies capable of neutralizing heterologous strains of HIV in peripheral blood mononuclear cell-, MAGI cell-, and U87-based infectivity assays. These data indicate that it is possible to create an immunogen by using formaldehyde-treated, thermally inactivated HIV-1 virions to induce neutralizing antibodies. These findings have broad implications for vaccine development.

scholarly journals Cellular Immune Responses of Schistosomiasis Patients Are Altered by Human Immunodeficiency Virus Type 1 Coinfection

2001 ◽  
Vol 184 (4) ◽  
pp. 488-496 ◽  
Author(s):  
Pauline N. M. Mwinzi ◽  
Diana M. S. Karanja ◽  
Daniel G. Colley ◽  
Alloys S. S. Orago ◽  
W. Evan Secor
Keyword(s):  
Human Immunodeficiency Virus ◽  
Immune Responses ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Cellular Immune Responses ◽  
Immunodeficiency Virus ◽  
Cellular Immune

CD8 T-Cell Infiltration in Extravascular Tissues of Patients With Human Immunodeficiency Virus Infection. Interleukin-15 Upmodulates Costimulatory Pathways Involved in the Antigen-Presenting Cells–T-Cell Interaction

Blood ◽  
1999 ◽  
Vol 93 (4) ◽  
pp. 1277-1286 ◽  
Author(s):  
Carlo Agostini ◽  
Renato Zambello ◽  
Monica Facco ◽  
Alessandra Perin ◽  
Francesco Piazza ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
T Cell ◽  
Hiv Infection ◽  
Binding Proteins ◽  
Antigen Presenting Cells ◽  
Cd8 T Cell ◽  
Immunodeficiency Virus ◽  
Ifn Γ ◽  
Antigen Presenting

Interleukin (IL)-15 regulates the proliferative activity of the CD8+ T-cell pool in human immunodeficiency virus (HIV)-infected patients, thereby contributing to the maintenance of the CD8+ T-cell–mediated immune response against HIV in extravascular tissues, including the lung. However, the effects of IL-15 on antigen-presenting cells (APC) during HIV infection are still unclear. In this study, we evaluated whether IL-15 regulates the macrophage stimulatory pathways governing inflammatory events that take place in the lung of patients with HIV infection. As a first step we evaluated the in vitro effects of IL-15 on lung macrophages retrieved from the respiratory tract of eight normal subjects. Although macrophages from uninfected individuals expressed the IL-15 binding proteins (IL-15R and the common γc) at resting conditions, they did not express IL-15 messenger RNA (mRNA). However, a 24-hour stimulation with IL-15 induced the expression of interferon-γ (IFN-γ) and IL-15 itself, suggesting a role for this cytokine in the activation of the pulmonary macrophage pool during inflammation. As a confirmation of the role of IL-15 in this setting, at resting conditions, alveolar macrophages of patients with HIV infection and T-cell alveolitis expressed IL-15, IFN-γ, and IL-15 binding proteins; showed an upmodulation of costimulatory molecules, B7 and CD72, which are involved in the APC of macrophages; and behaved as effective accessory cells because they elicited a strong proliferation of T cells. The accessory effect was inhibited by pretreatment with anti-CD72, anti-B7 (CD80 and CD86), and anti–IL-15 monoclonal antibodies (MoAb). We then investigated the relationship between IL-15 and the expression of costimulatory molecules by macrophages. A 24-hour stimulation of IL-15R+/γc+ macrophages with IL-15 upregulated the expression of CD80 and CD86. The evidence that IL-15 upregulates the expression of coligands that favor the contact between T cells and APC, per se, triggers T-cell activation and proliferation and acts as a chemoattractant for T cells, suggests that IL-15 plays a key role in Tc1-mediated defense mechanisms taking place in extravascular tissues of patients with HIV disease.

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