VIH et immunodéficiences acquises
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VIH et immunodéficiences acquises

ce n'est pas un Club de la SFI en 2014, mais pourquoi ne pas aussi suivre l'actualité sur un sujet si vaste et toujours d'actualité

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HIV-1-Specific IgA Monoclonal Antibodies from an HIV-1 Vaccinee Mediate Galactosylceramide Blocking and Phagocytosis


Via Gilbert C FAURE
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Frontiers | Human Immunodeficiency Virus Type-1 Elite Controllers Maintain Low Co-Expression of Inhibitory Receptors on CD4+ T Cells | Immunology

Frontiers | Human Immunodeficiency Virus Type-1 Elite Controllers Maintain Low Co-Expression of Inhibitory Receptors on CD4+ T Cells | Immunology | VIH et immunodéficiences acquises | Scoop.it
HIV-1 Elite Controllers (ELCs) represent a unique population that control viral replication in the absence of antiretroviral therapy (cART). It is well established that expression of multiple inhibitory receptors on CD8+ T cells is associated with HIV-1 disease progression. However, whether reduced co-expression of inhibitory receptors on CD4+ T cells is linked to natural viral control and slow HIV-1 disease progression remains undefined. Here, we report on the expression pattern of numerous measurable inhibitory receptors, associated with T cell exhaustion (PD-1, CTLA-4 and TIGIT), on different CD4+ T cell memory populations in ELCs and HIV-infected subjects with or without long-term cART. We found that the co-expression pattern of inhibitory receptors was significantly reduced in ELCs compared to HIV-1 cART-treated and viremic subjects, and similar to healthy controls. Markers associated with T cell exhaustion varied among different memory CD4+ T cell subsets and highest levels were found mainly on transitional memory T cells. CD4+ T cells co-expressing all inhibitory markers were positively correlated to T cell activation (CD38+HLA-DR+) as well as the transcription factors Helios and FoxP3. Finally, clinical parameters such as CD4 count, HIV-1 viral load and the CD4/CD8 ratio all showed significant associations with CD4+ T cell exhaustion. We demonstrate that ELCs are able to maintain lower levels of CD4+ T cell exhaustion despite years of ongoing viral replication compared to successfully cART treated subjects. Our findings suggest that ELCs harbor a “healthy” state of inhibitory receptor expression on CD4+ T cells that might play part in maintenance of their control status.
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Progress toward active or passive HIV-1 vaccination

Progress toward active or passive HIV-1 vaccination | VIH et immunodéficiences acquises | Scoop.it
AIDS is a preventable disease. Nevertheless, according to UNAIDS, 2.1 million individuals were infected with HIV-1 in 2015 worldwide. An effective vaccine is highly desirable. Most vaccines in clinical use today prevent infection because they elicit antibodies that block pathogen entry. Consistent with this general rule, studies in experimental animals have shown that broadly neutralizing antibodies to HIV-1 can prevent infection, suggesting that a vaccine that elicits such antibodies would be protective. However, despite significant efforts over the last 30 years, attempts to elicit broadly HIV-1 neutralizing antibodies by vaccination failed until recent experiments in genetically engineered mice were finally successful. Here, we review the key breakthroughs and remaining obstacles to the development of active and passive HIV-1 vaccines.
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Frontiers | Increasing the Clinical Potential and Applications of Anti-HIV Antibodies | Immunology

Frontiers | Increasing the Clinical Potential and Applications of Anti-HIV Antibodies | Immunology | VIH et immunodéficiences acquises | Scoop.it
Preclinical and early human clinical studies of broadly neutralizing antibodies (bNAbs) to prevent and treat HIV infection support the cinical utility and potential of bNAbs for prevention, post-exposure prophylaxis, and treatment of acute and chronic infection. Observed and potential limitations of bNAbs from these recent studies include the selection of resistant viral populations, immunogenicity resulting in the development of anti-drug (Ab) responses, and the potentially toxic elimination of reservoir cells in regeneration-limited tissues. Here, we review opportunities to improve the clinical utility of HIV Abs to address these challenges and further accomplish functional targets for anti-HIV Ab therapy at various stages of exposure/infection. Before exposure, bNAbs’ ability to serve as prophylaxis by neutralization may be improved by increasing serum half-life to necessitate less frequent administration, delivering genes for durable in vivo expression, and targeting bNAbs to sites of exposure. After exposure and/or in the setting of acute infection, bNAb use to prevent/reduce viral reservoir establishment and spread may be enhanced by increasing the potency with which autologous adaptive immune responses are stimulated, clearing acutely infected cells, and preventing cell-cell transmission of virus. In the setting of chronic infection, bNAbs may better mediate viral remission or “cure” in combination with anti-retroviral therapy and/or latency reversing agents, by targeting additional markers of tissue reservoirs or infected cell types, or by serving as targeting moieties in engineered cell therapy. While the clinical use of HIV Abs has never been closer, remaining studies to precisely define, model, and understand the complex roles and dynamics of HIV Abs and viral evolution in the context of the human immune system and anatomical compartmentalization will be critical to both optimize their clinical use in combination with existing agents and define further strategies with which to enhance their clinical safety and efficacy.
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Participer à la riposte au sida

Participer à la riposte au sida | VIH et immunodéficiences acquises | Scoop.it
Agir Participer à la riposte au sida PRÉSENTATION Depuis la découverte des premiers cas de VIH il y a plus de 35 ans en arrière, 78 millions de personnes ont été infectées par le VIH et 35 millions sont décédées de maladies liées au sida.
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Ageing and inflammation in patients with HIV infection

Ageing and inflammation in patients with HIV infection | VIH et immunodéficiences acquises | Scoop.it
Nowadays, HIV+ patients have an expected lifespan that is only slightly shorter than healthy individuals. For this reason, along with the fact that infection can be acquired at a relatively advance
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Detection of HIV-1-specific gastrointestinal tissue resident CD8+ T-cells in chronic infection

Detection of HIV-1-specific gastrointestinal tissue resident CD8+ T-cells in chronic infection | VIH et immunodéficiences acquises | Scoop.it
Article

Via Gilbert C FAURE
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JCI Insight - Reevaluation of immune activation in the era of cART and an aging HIV-infected population

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Role of HIV-specific CD8+ T cells in pediatric HIV cure strategies after widespread early viral escape

Role of HIV-specific CD8+ T cells in pediatric HIV cure strategies after widespread early viral escape | VIH et immunodéficiences acquises | Scoop.it
Recent studies have suggested greater HIV cure potential among infected children than adults. A major obstacle to HIV eradication in adults is that the viral reservoir is largely comprised of HIV-specific cytotoxic T lymphocyte (CTL) escape variants. We here evaluate the potential for CTL in HIV-infected slow-progressor children to play an effective role in “shock-and-kill” cure strategies. Two distinct subgroups of children were identified on the basis of viral load. Unexpectedly, in both groups, as in adults, HIV-specific CTL drove the selection of escape variants across a range of epitopes within the first weeks of infection. However, in HIV-infected children, but not adults, de novo autologous variant-specific CTL responses were generated, enabling the pediatric immune system to “corner” the virus. Thus, even when escape variants are selected in early infection, the capacity in children to generate variant-specific anti-HIV CTL responses maintains the potential for CTL to contribute to effective shock-and-kill cure strategies in pediatric HIV infection.
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Study clears important hurdle towards developing an HIV vaccine

Study clears important hurdle towards developing an HIV vaccine | VIH et immunodéficiences acquises | Scoop.it
In a study published in 2009, results from a clinical trial carried out in Thailand found that an experimental vaccine against HIV lowered the rate of human infection by 31%. This gave cautious optimism that a vaccine against the virus might be a feasible prospect. A vaccine has obvious advantages over treatment with anti-retroviral drugs in that prevention could lead to eradication.
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Membrane-anchored CCL20 augments HIV Env-specific mucosal immune responses. - PubMed - NCBI

Membrane-anchored CCL20 augments HIV Env-specific mucosal immune responses. - PubMed - NCBI | VIH et immunodéficiences acquises | Scoop.it
Virol J. 2017 Aug 23;14(1):163. doi: 10.1186/s12985-017-0831-4.
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Frontiers | Role of Different Subpopulations of CD8+ T Cells during HIV Exposure and Infection | Immunology

Frontiers | Role of Different Subpopulations of CD8+ T Cells during HIV Exposure and Infection | Immunology | VIH et immunodéficiences acquises | Scoop.it
During HIV infection, specific responses exhibited by CD8+ T cells are crucial to establish an early, effective, and sustained viral control, preventing severe immune alterations and organ dysfunction. Several CD8+ T cells subsets have been identified, exhibiting differences in terms of activation, functional profile, and ability to limit HIV replication. Some of the most important CD8+ T cells subsets associated with viral control, production of potent antiviral molecules, and strong polyfunctional responses include Th1-like cytokine pattern and Tc17 cells. In addition, the expression of specific activation markers has been also associated with a more effective response of CD8+ T cells, as evidenced in HLA-DR+ CD38− cells. CD8+ T cells in both, peripheral blood and gut mucosa, are particularly important in individuals with a resistant phenotype, including HIV-exposed seronegative individuals (HESNs), long-term non-progressors (LTNPs) and HIV-controllers. Although the role of CD8+ T cells has been extensively explored in the context of an established HIV-1 infection, the presence of HIV-specific cells with effector abilities and a defined functional profile in HESNs, remain poorly understood. Here, we reviewed studies carried out on different subpopulations of CD8+ T cells in relation with natural resistance to HIV infection and progression.


Via Marcelo de Carvalho Bittencourt
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Frontiers | Human Intestinal Epithelial Cells Release Antiviral Factors That Inhibit HIV Infection of Macrophages | Immunology

Frontiers | Human Intestinal Epithelial Cells Release Antiviral Factors That Inhibit HIV Infection of Macrophages | Immunology | VIH et immunodéficiences acquises | Scoop.it
As a rich source of CD4+ T cells and macrophages, the gastrointestinal (GI) tract is a major target site for HIV infection. The interplay between GI resident macrophages and intestinal epithelial cells (IECs) constitutes an important element of GI innate immunity against pathogens. In this study, we investigated whether human IECs have the ability to produce antiviral factors that can inhibit HIV infection of macrophages. We demonstrated that IECs possess functional toll-like receptor 3 (TLR3), the activation of which resulted in induction of key IFN regulatory factors (IRF3 and IRF7), IFN-β, IFN-λ and CC chemokines (MIP-1α, MIP-1β, RANTES), the ligands of HIV entry co-receptor CCR5. In addition, TLR3-activated IECs release exosomes that contained the anti-HIV factors, including IFN stimulated genes (ISGs: ISG15, ISG56, MxB, OAS-1, GBP5, and Viperin) and HIV restriction miRNAs (miRNA-17, miRNA-20, miRNA-28, miRNA-29 family members and miRNA-125b). Importantly, treatment of macrophages with supernatant (SN) from the activated IEC cultures inhibited HIV replication. Further studies showed that IEC SN could also induce the expression of antiviral ISGs and cellular HIV restriction factors (Tetherin and APOBEC3G/3F) in HIV-infected macrophages. These findings indicated that IECs might act as an important element in GI innate immunity against HIV infection/replication.

Via Gilbert C FAURE
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JCI Insight - Fine epitope signature of antibody neutralization breadth at the HIV-1 envelope CD4-binding site

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Can gene therapy be harnessed to fight the AIDS virus?

Can gene therapy be harnessed to fight the AIDS virus? | VIH et immunodéficiences acquises | Scoop.it
For more than a decade, the strongest AIDS drugs could not fully control Matt Chappell's HIV infection. Now his body controls it by itself, and researchers are trying to perfect the gene editing that made this possible.

Via Krishan Maggon
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Case report: mechanisms of HIV elite control in two African women

Case report: mechanisms of HIV elite control in two African women | VIH et immunodéficiences acquises | Scoop.it
The majority of people living with HIV require antiretroviral therapy (ART) for controlling viral replication, however there are rare HIV controllers who spontaneously and durably control HIV in the absence of treatment. Understanding what mediates viral control in these individuals has provided us with insights into the immune mechanisms that may be important to induce for a vaccine or functional cure for HIV. To date, few African elite controllers from high incidence settings have been described. We identified virological controllers from the CAPRISA 002 cohort of HIV-1 subtype C infected women in KwaZulu Natal, South Africa, two (1%) of whom were elite controllers. We examined the genetic, clinical, immunological and virological characteristics of these two elite HIV controllers in detail, to determine whether they exhibit features of putative viral control similar to those described for elite controllers reported in the literature. In this case report, we present clinical features, CD4+ T cell and viral load trajectories for two African women over 7 years of HIV infection. Viral load became undetectable 10 months after HIV infection in Elite Controller 1 (EC1), and after 6 weeks in Elite Controller 2 (EC2), and remained undetectable for the duration of follow-up, in the absence of ART. Both elite controllers expressed multiple HLA Class I and II haplotypes previously associated with slower disease progression (HLA-A*74:01, HLA-B*44:03, HLA-B*81:01, HLA-B*57:03, HLA-DRB1*13). Fitness assays revealed that both women were infected with replication competent viruses, and both expressed higher mRNA levels of p21, a host restriction factor associated with viral control. HIV-specific T cell responses were examined using flow cytometry. EC1 mounted high frequency HIV-specific CD8+ T cell responses, including a B*81:01-restricted Gag TL9 response. Unusually, EC2 had evidence of pre-infection HIV-specific CD4+ T cell responses. We identified some features typical of elite controllers, including high magnitude HIV-specific responses and beneficial HLA. In addition, we made the atypical finding of pre-infection HIV-specific immunity in one elite controller, that may have contributed to very early viral control. This report highlights the importance of studying HIV controllers in high incidence settings.
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Human Immunodeficiency Virus type-1 (HIV-1) evades antibody-dependent phagocytosis

Human Immunodeficiency Virus type-1 (HIV-1) evades antibody-dependent phagocytosis | VIH et immunodéficiences acquises | Scoop.it
Author summary Antibody-dependent phagocytosis (ADP) of virus particles is thought to play a role in clearing some viral infections. However, it is unclear what role, if any, ADP plays in preventing or controlling HIV-1 infection. We sought to directly determine if antibodies could mediate the internalization of HIV-1 into phagocytes. We found that despite the ability of tested antibodies to bind to and at times neutralize the infectivity of HIV-1, they were very inefficient at internalizing the virus into monocytes and other phagocytic cells. We further demonstrated that poor ADP activity was due to the limited number of envelope spikes found on the surface of HIV-1. Related to the low number of spikes, antibodies were inefficient at aggregating the virus, a phenomenon that was key for effective phagocytosis. On the other hand, antibodies were capable of either shearing the membrane of or internalizing cells that were coated with HIV-1. Our results cast doubt on a key role for ADP in preventing HIV-1 infection and suggest that other antibody functions are more important.
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Functional advantage of educated KIR2DL1+ natural killer cells for anti‐HIV‐1 antibody‐dependent activation

Functional advantage of educated KIR2DL1+ natural killer cells for anti‐HIV‐1 antibody‐dependent activation | VIH et immunodéficiences acquises | Scoop.it
Evidence from the RV144 HIV‐1 vaccine trial implicates anti‐HIV‐1 antibody‐dependent cellular cytotoxicity (ADCC) in vaccine‐conferred protection from infection. Among effector cells that mediat
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Frontiers | Differential Relationships among Circulating Inflammatory and Immune Activation Biomediators and Impact of Aging and Human Immunodeficiency Virus Infection in a Cohort of Injection Drug...

Frontiers | Differential Relationships among Circulating Inflammatory and Immune Activation Biomediators and Impact of Aging and Human Immunodeficiency Virus Infection in a Cohort of Injection Drug... | VIH et immunodéficiences acquises | Scoop.it
As individuals with human immunodeficiency virus (HIV) infection live longer, aging and age-related chronic conditions have become major health concerns for this vulnerable population. Substantial evidence suggests that chronic inflammation and immune activation contribute significantly to chronic conditions in people aging with or without HIV infection. As a result, increasing numbers of inflammation and immune activation biomediators have been measured. While very few studies describe their in vivo relationships, such studies can serve as an important and necessary initial step towards delineating the complex network of chronic inflammation and immune activation. In this study, we evaluated in vivo relationships between serum levels of neopterin, a biomediator of immune activation, and 4 commonly described inflammatory biomediators: soluble tumor necrosis factor (TNF)-alpha receptor (sTNFR)-1, sTNFR-2, interleukin (IL)-6, and C-reactive protein (CRP), as well as the impact of HIV infection and aging in the AIDS Linked to the Intravenous Experience (ALIVE) study, a community-recruited observational study of former and current injection drug users (IDUs) with or at high risk for HIV infection in Baltimore, MD. The study included 1178 participants in total with 316 HIV-infected (HV+) and 862 HIV-uninfected (HIV-) IDUs. Multivariate regression analyses were employed, adjusting for age, sex, BMI, smoking, hepatitis C virus co-infection, injection drug use, comorbidities, and HIV status (for all participants), and HIV viral load, CD4+ T-cell counts, and anti-retroviral therapy (for HIV+ participants). The results showed significant impact of aging on all five biomediators and that of HIV infection on all but sTNFR-1. In the adjusted model, neopterin had positive associations with sTNFR-1 and sTNFR-2 (partial correlation coefficients: 0.269 and 0.422 respectively for all participants; 0.292 and 0.354 for HIV+; and 0.262 and 0.435 for HIV-, all p< .0001). No significant associations between neopterin and IL-6 or CRP were identified. Such differential relationships between circulating neopterin and sTNFR-1, sTNFR-2, IL-6, and CRP may help inform their selection in future studies. These findings may also facilitate elucidation of underlying inflammatory and immune activation pathways that contribute to age-related chronic conditions, potentially leading to identification of key biomediators, particularly those upstream of CRP, as novel targets for intervention.
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HIV vaccine candidate: Spurs animals to produce antibodies against protective sugars of multiple HIV strains - Outbreak News Today

HIV vaccine candidate: Spurs animals to produce antibodies against protective sugars of multiple HIV strains - Outbreak News Today | VIH et immunodéficiences acquises | Scoop.it
Researchers at the University of Maryland and Duke University have designed a novel protein-sugar vaccine candidate that, in an animal model, stimulated an immune response against sugars that form a protective shield around HIV. The molecule could one day become part of a successful HIV vaccine. “An obstacle to creating an effective HIV vaccine is …
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Sida : des cellules du système immunitaire inné (NK) contrôlent la réplication du virus dans les ganglions lymphatiques

Sida : des cellules du système immunitaire inné (NK) contrôlent la réplication du virus dans les ganglions lymphatiques | VIH et immunodéficiences acquises | Scoop.it
Sida : des cellules du système immunitaire inné (NK) contrôlent la réplication du virus dans les ganglions lymphatiques. Retrouvez toute l'actualité et les projets de l'Institut Pasteur sur son site.
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Current Peptide and Protein Candidates Challenging HIV Therapy beyond the Vaccine Era

Current Peptide and Protein Candidates Challenging HIV Therapy beyond the Vaccine Era | VIH et immunodéficiences acquises | Scoop.it
Human immunodeficiency virus (HIV) is a causative agent of acquired immune deficiency syndrome (AIDS). Highly active antiretroviral therapy (HAART) can slow down the replication of HIV-1, leading to an improvement in the survival of HIV-1-infected patients. However, drug toxicities and poor drug administration has led to the emergence of a drug-resistant strain. HIV-1 immunotherapy has been continuously developed, but antibody therapy and HIV vaccines take time to improve its efficiency and have limitations. HIV-1-specific chimeric antigen receptor (CAR)-based immunotherapy founded on neutralizing antibodies is now being developed. In HIV-1 therapy, anti-HIV chimeric antigen receptors showed promising data in the suppression of HIV-1 replication; however, autologous transfusion is still a problem. This has led to the development of effective peptides and proteins for an alternative HIV-1 treatment. In this paper, we provide a comprehensive review of potent anti-HIV-1 peptides and proteins that reveal promising therapeutic activities. The inhibitory mechanisms of each therapeutic molecule in the different stages of the HIV-1 life cycle will be discussed herein.
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JCI Insight - HDAC inhibition induces HIV-1 protein and enables immune-based clearance following latency reversal

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HIV Nef protein implicated in cardiomyopathy | Immunopaedia

HIV Nef protein implicated in cardiomyopathy | Immunopaedia | VIH et immunodéficiences acquises | Scoop.it
HIV infection often leads to cardiovascular disease, however, the mechanism behind this was not well understood. Researchers, led by Kamel Khalili
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Immunology and Cell Biology - Factoring in CD4 T cells during treatment of HIV

Immunology and Cell Biology - Factoring in CD4 T cells during treatment of HIV | VIH et immunodéficiences acquises | Scoop.it
Immunology and Cell Biology focuses on the general functioning of the immune system in its broadest sense, with a particular emphasis on its cell biology. Areas that are covered include but are not limited to: Cellular immunology, Innate and adaptive immunity, Immune responses to pathogens,Tumour immunology,Immunopathology, Immunotherapy, Immunogenetics, Immunological studies in humans and model organisms (including mouse, rat, Drosophila etc)
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