Faculty Opinions recommendation of Enzymatic removal of mannose moieties can increase the immune response to HIV-1 gp120 in vivo.

2009 ◽  
Author(s):  
Luigi Buonaguro
Keyword(s):  
Immune Response ◽  
Hiv 1

scholarly journals X4 Human Immunodeficiency Virus Type 1 gp120 Down-Modulates Expression and Immunogenicity of Codelivered Antigens

2009 ◽  
Vol 83 (21) ◽  
pp. 10941-10950 ◽  
Author(s):  
Avi-Hai Hovav ◽  
Michael Santosuosso ◽  
Maytal Bivas-Benita ◽  
Andre Plair ◽  
Alex Cheng ◽  
...  
Keyword(s):  
Immune Response ◽  
Human Immunodeficiency Virus ◽  
Antigen Presentation ◽  
Antigen Expression ◽  
V3 Loop ◽  
Humoral Immune ◽  
Immunodeficiency Virus ◽  
Aids Vaccines ◽  
Hiv 1

ABSTRACT In order to increase the immune breadth of human immunodeficiency virus (HIV) vaccines, strategies such as immunization with several HIV antigens or centralized immunogens have been examined. HIV-1 gp120 protein is a major immunogen of HIV and has been routinely considered for inclusion in both present and future AIDS vaccines. However, recent studies proposed that gp120 interferes with the generation of immune response to codelivered antigens. Here, we investigate whether coimmunization with plasmid-encoded gp120 alters the immune response to other coadministered plasmid encoded antigens such as luciferase or ovalbumin in a mouse model. We found that the presence of gp120 leads to a significant reduction in the expression level of the codelivered antigen in vivo. Antigen presentation by antigen-presenting cells was also reduced and resulted in the induction of weak antigen-specific cellular and humoral immune responses. Importantly, gp120-mediated immune interference was observed after administration of the plasmids at the same or at distinct locations. To characterize the region in gp120 mediating these effects, we used plasmid constructs encoding gp120 that lacks the V1V2 loops (ΔV1V2) or the V3 loop (ΔV3). After immunization, the ΔV1V2, but not the ΔV3 construct, was able to reduce antigen expression, antigen presentation, and subsequently the immunogenicity of the codelivered antigen. The V3 loop dependence of this phenomenon seems to be limited to V3 loops known to interact with the CXCR4 molecule but not with CCR5. Our study presents a novel mechanism by which HIV-1 gp120 interferes with the immune response against coadministered antigen in a polyvalent vaccine preparation.

scholarly journals Enzymatic removal of mannose moieties can increase the immune response to HIV-1 gp120 in vivo

Virology ◽  
2009 ◽  
Vol 389 (1-2) ◽  
pp. 108-121 ◽  
Author(s):  
Kaustuv Banerjee ◽  
Sofija Andjelic ◽  
Per Johan Klasse ◽  
Yun Kang ◽  
Rogier W. Sanders ◽  
...  
Keyword(s):  
Immune Response ◽  
Hiv 1

HIV-1 STRATEGIES OF IMMUNE EVASION

2005 ◽  
Vol 16 (12) ◽  
pp. 1869-1878 ◽  
Author(s):  
F. CASTIGLIONE ◽  
M. BERNASCHI
Keyword(s):  
Immune Response ◽  
Disease Progression ◽  
Computer Model ◽  
Immune Evasion ◽  
Selective Pressure ◽  
Computer Experiments ◽  
Replication Rate ◽  
Hiv 1

We simulate the progression of the HIV-1 infection in untreated host organisms. The phenotype features of the virus are represented by the replication rate, the probability of activating the transcription, the mutation rate and the capacity to stimulate an immune response (the so-called immunogenicity). It is very difficult to study in-vivo or in-vitro how these characteristics of the virus influence the evolution of the disease. Therefore we resorted to simulations based on a computer model validated in previous studies. We observe, by means of computer experiments, that the virus continuously evolves under the selective pressure of an immune response whose effectiveness downgrades along with the disease progression. The results of the simulations show that immunogenicity is the most important factor in determining the rate of disease progression but, by itself, it is not sufficient to drive the disease to a conclusion in all cases.

Platelet Derived CD154 Induced by Tat Contributes to HIV-1 Associated Autoimmune Thrombocytopenia.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2669-2669
Author(s):  
Jianhui Wang ◽  
Wei Zhang ◽  
Zongdong Li
Keyword(s):  
Immune Response ◽  
Platelet Activation ◽  
Conflicts Of Interest ◽  
Calcium Flux ◽  
Tat Protein ◽  
Autoimmune Thrombocytopenia ◽  
Integrin Β3 ◽  
Hiv 1

Abstract Abstract 2669 Poster Board II-645 Enhanced platelet activation was reported in HIV-1 infected patients and strongly correlated with plasma viral load. The HIV-1 Tat protein is able to serve as a ligand of the integrin αvβ3 and several chemokine receptors (CCR2 and CCR3) and to induce downstream signaling in cells express those receptors but the effect of Tat on platelet activation has not been fully investigated yet. Activated platelets are known to express and release a variety of proteins that can modulate the immune system, and platelet derived CD154 is reportedly involved in the development of autoimmune thrombocytopenia. However, the full mechanism underlying HIV-1 induced platelet activation and the biological consequences are not completely understood. In this study, we demonstrate that Tat is able to interact with platelets and β3 integrin by S35 label Tat-platelet binding assay and GST-Tat protein pull-down. We then show that Tat is able to induce platelet activation, up-regulates both CD62P and CD154 in both mouse and human platelets, and results in micro-particle release (as demonstrated by electron microscopy). Tat induces greatly diminished activation in integrin β3 knock out platelets or in platelets pretreated with CCR3 or calcium flux inhibitors, suggesting the requirement of chemokine receptor CCR3, integrin β3 and calcium flux for Tat induced platelet activation. The effect of Tat induced platelet activation on the immune response was studied both in vitro and in vivo. An enhanced immunoglobulin class switch was found in mouse spleen B cells co-cultured with platelets treated with Tat in vitro. In addition, an early antibody response against adenovirus was found in Tat injected mouse immunized with adenovirus suggesting an enhanced immune response in vivo. Thus, we have described a new mechanism in which Tat is able to induce platelet activation and have generated a model in which platelet activation can contribute to the development of HIV-1 associated thrombocytopenia. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Global Stability of HIV-1 Infection Model with Two Time Delays

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Hui Miao ◽  
Xamxinur Abdurahman ◽  
Ahmadjan Muhammadhaji
Keyword(s):  
Immune Response ◽  
Delay Differential Equations ◽  
Time Delays ◽  
Infection Model ◽  
Global Dynamics ◽  
Response Model ◽  
Delay Differential ◽  
Ctl Immune Response ◽  
Hiv 1

We investigate global dynamics for a system of delay differential equations which describes a virus-immune interaction in vivo. The model has two time delays describing time needed for infection of cell and CTLs generation. Our model admits three possible equilibria: infection-free equilibrium, CTL-absent infection equilibrium, and CTL-present infection equilibrium. The effect of time delay on stability of the equilibria of the CTL immune response model has been studied.

HIV-1 POPULATION DYNAMICS IN VIVO: IMPLICATIONS FOR PATHOGENESIS, EFFECT OF CYTOKINE AND THERAPY STRATEGY

2004 ◽  
Vol 12 (03) ◽  
pp. 315-333
Author(s):  
JIE LOU ◽  
ZHIEN MA ◽  
MEIZHI LOU ◽  
YIMING SHAO
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune System ◽  
Immune Escape ◽  
Interleukin 2 ◽  
Human Immune System ◽  
Therapy Strategy ◽  
The Impact ◽  
Hiv 1

In this paper, we present a dynamical model to study the spread of HIV-1 in vivo. Our goal is to better understand the interaction between HIV-1 and the human immune system. Making use of the Hill function, we describe two kinds of processions occurring in the immune response: the activation interactions or inhibitory interactions occurring between different components in the immune response, and the autocatalytic maintenance of the CD4+ T cells and CD8+ T cells populations. We also consider the impact of the cytokine interleukin-2 (IL-2) and the CD8 antiviral factor (CAF) on HIV-1 infection. Through numerical simulations we get several results. First, we find that the effects of IL-2 and CAF in the treatment for the infected are limiting. Namely, the curative effect will not always increase along with the dose of IL-2 or CAF or both. The increasing trend will stagnate at a certain dose that we used. Second, we find some possible reasons for the collapse of the lymph system in HIV-1 infection — the loss of these restraining functions, and/or the genetic variability of the virus due to immune escape that enhances the virulence, which then bring the collapse of the immune system. In some conditions the system will produce a Hopf bifurcation. We also simulate the theoretical warrant of the feasibility of the combined chemotherapy strategies for the HIV-1 infected patient.

scholarly journals Effect of Plasmid DNA Vaccine Design and In Vivo Electroporation on the Resulting Vaccine-Specific Immune Responses in Rhesus Macaques

2007 ◽  
Vol 81 (10) ◽  
pp. 5257-5269 ◽  
Author(s):  
Amara Luckay ◽  
Maninder K. Sidhu ◽  
Rune Kjeken ◽  
Shakuntala Megati ◽  
Siew-Yen Chong ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Plasmid Dna ◽  
Vaccine Design ◽  
Fold Increase ◽  
Specific Cell ◽  
In Vivo Electroporation ◽  
High Molecular Weight Dna ◽  
Hiv 1

ABSTRACT Since human immunodeficiency virus (HIV)-specific cell-mediated immune (CMI) responses are critical in the early control and resolution of HIV infection and correlate with postchallenge outcomes in rhesus macaque challenge experiments, we sought to identify a plasmid DNA (pDNA) vaccine design capable of eliciting robust and balanced CMI responses to multiple HIV type 1 (HIV-1)-derived antigens for further development. Previously, a number of two-, three-, and four-vector pDNA vaccine designs were identified as capable of eliciting HIV-1 antigen-specific CMI responses in mice (M. A. Egan et al., Vaccine 24:4510-4523, 2006). We then sought to further characterize the relative immunogenicities of these two-, three-, and four-vector pDNA vaccine designs in nonhuman primates and to determine the extent to which in vivo electroporation (EP) could improve the resulting immune responses. The results indicated that a two-vector pDNA vaccine design elicited the most robust and balanced CMI response. In addition, vaccination in combination with in vivo EP led to a more rapid onset and enhanced vaccine-specific immune responses. In macaques immunized in combination with in vivo EP, we observed a 10- to 40-fold increase in HIV-specific enzyme-linked immunospot assay responses compared to those for macaques receiving a 5-fold higher dose of vaccine without in vivo EP. This increase in CMI responses translates to an apparent 50- to 200-fold increase in pDNA vaccine potency. Importantly, in vivo EP enhanced the immune response against the less immunogenic antigens, resulting in a more balanced immune response. In addition, in vivo EP resulted in an approximate 2.5-log10 increase in antibody responses. The results further indicated that in vivo EP was associated with a significant reduction in pDNA persistence and did not result in an increase in pDNA associated with high-molecular-weight DNA relative to macaques receiving the pDNA without EP. Collectively, these results have important implications for the design and development of an efficacious vaccine for the prevention of HIV-1 infection.

scholarly journals A Polylactide-Based Micellar Adjuvant Improves the Intensity and Quality of Immune Response

Pharmaceutics ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 107
Author(s):  
Myriam Lamrayah ◽  
Capucine Phelip ◽  
Céline Coiffier ◽  
Céline Lacroix ◽  
Thibaut Willemin ◽  
...  
Keyword(s):  
Immune Response ◽  
Near Infrared ◽  
Humoral Response ◽  
Elisa Test ◽  
Time Range ◽  
Micellar Systems ◽  
Hiv 1 ◽  
Gold Standards

Micelles from amphiphilic polylactide-block-poly(N-acryloxysuccinimide-co-N-vinylpyrrolidone) (PLA-b-P(NAS-co-NVP)) block copolymers of 105 nm in size were characterized and evaluated in a vaccine context. The micelles were non-toxic in vitro (both in dendritic cells and HeLa cells). In vitro fluorescence experiments combined with in vivo fluorescence tomography imaging, through micelle loading with the DiR near infrared probe, suggested an efficient uptake of the micelles by the immune cells. The antigenic protein p24 of the HIV-1 was successfully coupled on the micelles using the reactive N-succinimidyl ester groups on the micelle corona, as shown by SDS-PAGE analyses. The antigenicity of the coupled antigen was preserved and even improved, as assessed by the immuno-enzymatic (ELISA) test. Then, the performances of the micelles in immunization were investigated and compared to different p24-coated PLA nanoparticles, as well as Alum and MF59 gold standards, following a standardized HIV-1 immunization protocol in mice. The humoral response intensity (IgG titers) was substantially similar between the PLA micelles and all other adjuvants over an extended time range (one year). More interestingly, this immune response induced by PLA micelles was qualitatively higher than the gold standards and PLA nanoparticles analogs, expressed through an increasing avidity index over time (>60% at day 365). Taken together, these results demonstrate the potential of such small-sized micellar systems for vaccine delivery.

scholarly journals Double immunocytochemical staining for in vivo detection of epitope specificity and isotype of antibody-forming cells against synthetic peptides homologous to human immunodeficiency virus-1.

1990 ◽  
Vol 38 (4) ◽  
pp. 457-462 ◽  
Author(s):  
J D Laman ◽  
K Gerritse ◽  
M Fasbender ◽  
W J Boersma ◽  
N van Rooijen ◽  
...  
Keyword(s):  
Immune Response ◽  
Lymph Node ◽  
B Cell ◽  
Immune Complexes ◽  
Humoral Immune Response ◽  
Synthetic Peptides ◽  
Humoral Immune ◽  
Epitope Specificity ◽  
Hiv 1

Many infections evoke a strong humoral immune response. Some (e.g., HIV-1, EBV, CMV) also lead to disorders of the B-cell system. Data concerning cell dysfunction are largely derived from in vitro studies, which necessarily exclude all microenvironmental influences. The aim of this study was to develop a tool for the investigation of epitope specific humoral immune responses in vivo. Mice were immunized with one of two synthetic peptides, both 21 amino acids long and homologous to regions of the HIV-1 gp160. Cryostat sections of spleen and lymph nodes were incubated with the corresponding peptide coupled to alkaline phosphatase and simultaneously incubated with peroxidase-conjugated rabbit antisera specific for mouse immunoglobulin isotypes. We were able to show simultaneous detection of epitope specificity, isotype, and localization of antibody-forming cells and immune complexes in tissue sections. It should prove useful for in vivo investigation of the development of specific (e.g., anti-HIV-1) humoral immune response, the determination of B-cell specificity in lymph node infiltrates, and the role of immune complexes in lymph node pathology.

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