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  1. Article ; Online: Transient viral exposure drives functionally-coordinated humoral immune responses in HIV-1 post-treatment controllers

    Luis M. Molinos-Albert / Valérie Lorin / Valérie Monceaux / Sylvie Orr / Asma Essat / Jérémy Dufloo / Olivier Schwartz / Christine Rouzioux / Laurence Meyer / Laurent Hocqueloux / Asier Sáez-Cirión / Hugo Mouquet / ANRS VISCONTI Study Group

    Nature Communications, Vol 13, Iss 1, Pp 1-

    2022  Volume 17

    Abstract: A rare sub-population of people living with HIV-1 experience long-lasting viral remission after interrupting antiretroviral therapy and are considered post-treatment controllers. Here the authors characterise the humoral immune response to HIV-1 in a ... ...

    Abstract A rare sub-population of people living with HIV-1 experience long-lasting viral remission after interrupting antiretroviral therapy and are considered post-treatment controllers. Here the authors characterise the humoral immune response to HIV-1 in a cohort of post-treatment controllers.
    Keywords Science ; Q
    Language English
    Publishing date 2022-04-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Broadly neutralizing anti-HIV-1 antibodies tether viral particles at the surface of infected cells

    Jérémy Dufloo / Cyril Planchais / Stéphane Frémont / Valérie Lorin / Florence Guivel-Benhassine / Karl Stefic / Nicoletta Casartelli / Arnaud Echard / Philippe Roingeard / Hugo Mouquet / Olivier Schwartz / Timothée Bruel

    Nature Communications, Vol 13, Iss 1, Pp 1-

    2022  Volume 11

    Abstract: Broadly neutralizing antibodies (bNAbs) neutralize HIV-1 and exert Fc-dependent activities against infected cells. Here, Dufloo et al. show that bNAbs also block HIV-1 release by trapping viral particles at the surface of infected cells. ...

    Abstract Broadly neutralizing antibodies (bNAbs) neutralize HIV-1 and exert Fc-dependent activities against infected cells. Here, Dufloo et al. show that bNAbs also block HIV-1 release by trapping viral particles at the surface of infected cells.
    Keywords Science ; Q
    Language English
    Publishing date 2022-02-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Phagocytosis by an HIV antibody is associated with reduced viremia irrespective of enhanced complement lysis

    David A. Spencer / Benjamin S. Goldberg / Shilpi Pandey / Tracy Ordonez / Jérémy Dufloo / Philip Barnette / William F. Sutton / Heidi Henderson / Rebecca Agnor / Lina Gao / Timothée Bruel / Olivier Schwartz / Nancy L. Haigwood / Margaret E. Ackerman / Ann J. Hessell

    Nature Communications, Vol 13, Iss 1, Pp 1-

    2022  Volume 14

    Abstract: While antibodies neutralize HIV via Fab recognition of viral surface antigens, antibody Fc domains mediate effector functions, including antibody-dependent cellular phagocytosis (ADCP) and cytotoxicity (ADCC), and complement (C') activity. Here, Spencer ... ...

    Abstract While antibodies neutralize HIV via Fab recognition of viral surface antigens, antibody Fc domains mediate effector functions, including antibody-dependent cellular phagocytosis (ADCP) and cytotoxicity (ADCC), and complement (C') activity. Here, Spencer et al. modify bNAb 10E8v4 to enhance C'-mediated potency in SHIV challenged rhesus macaques to probe its function in protection, showing that in the absence of neutralization, enhancing C' activities in vitro adds no value toward reducing viremia in either blood or tissue.
    Keywords Science ; Q
    Language English
    Publishing date 2022-02-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Asymptomatic and symptomatic SARS-CoV-2 infections elicit polyfunctional antibodies

    Jérémy Dufloo / Ludivine Grzelak / Isabelle Staropoli / Yoann Madec / Laura Tondeur / François Anna / Stéphane Pelleau / Aurélie Wiedemann / Cyril Planchais / Julian Buchrieser / Rémy Robinot / Marie-Noelle Ungeheuer / Hugo Mouquet / Pierre Charneau / Michael White / Yves Lévy / Bruno Hoen / Arnaud Fontanet / Olivier Schwartz /
    Timothée Bruel

    Cell Reports Medicine, Vol 2, Iss 5, Pp 100275- (2021)

    2021  

    Abstract: Summary: Many SARS-CoV-2-infected individuals remain asymptomatic. Little is known about the extent and quality of their antiviral humoral response. Here, we analyze antibody functions in 52 asymptomatic infected individuals, 119 mildly symptomatic, and ... ...

    Abstract Summary: Many SARS-CoV-2-infected individuals remain asymptomatic. Little is known about the extent and quality of their antiviral humoral response. Here, we analyze antibody functions in 52 asymptomatic infected individuals, 119 mildly symptomatic, and 21 hospitalized patients with COVID-19. We measure anti-spike immunoglobulin G (IgG), IgA, and IgM levels with the S-Flow assay and map IgG-targeted epitopes with a Luminex assay. We also evaluate neutralization, complement deposition, and antibody-dependent cellular cytotoxicity (ADCC) using replication-competent SARS-CoV-2 or reporter cell systems. We show that COVID-19 sera mediate complement deposition and kill infected cells by ADCC. Sera from asymptomatic individuals neutralize the virus, activate ADCC, and trigger complement deposition. Antibody levels and functions are lower in asymptomatic individuals than they are in symptomatic cases. Antibody functions are correlated, regardless of disease severity. Longitudinal samplings show that antibody functions follow similar kinetics of induction and contraction. Overall, asymptomatic SARS-CoV-2 infection elicits polyfunctional antibodies neutralizing the virus and targeting infected cells.
    Keywords SARS-CoV-2 ; ADCC ; complement ; asymptomatic ; antibody ; Medicine (General) ; R5-920
    Subject code 570
    Language English
    Publishing date 2021-05-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Conformational Plasticity in Broadly Neutralizing HIV-1 Antibodies Triggers Polyreactivity

    Julie Prigent / Annaëlle Jarossay / Cyril Planchais / Caroline Eden / Jérémy Dufloo / Ayrin Kök / Valérie Lorin / Oxana Vratskikh / Thérèse Couderc / Timothée Bruel / Olivier Schwartz / Michael S. Seaman / Oliver Ohlenschläger / Jordan D. Dimitrov / Hugo Mouquet

    Cell Reports, Vol 23, Iss 9, Pp 2568-

    2018  Volume 2581

    Abstract: Human high-affinity antibodies to pathogens often recognize unrelated ligands. The molecular origin and the role of this polyreactivity are largely unknown. Here, we report that HIV-1 broadly neutralizing antibodies (bNAbs) are frequently polyreactive, ... ...

    Abstract Human high-affinity antibodies to pathogens often recognize unrelated ligands. The molecular origin and the role of this polyreactivity are largely unknown. Here, we report that HIV-1 broadly neutralizing antibodies (bNAbs) are frequently polyreactive, cross-reacting with non-HIV-1 molecules, including self-antigens. Mutating bNAb genes to increase HIV-1 binding and neutralization also results in de novo polyreactivity. Unliganded paratopes of polyreactive bNAbs with improved HIV-1 neutralization exhibit a conformational flexibility, which contributes to enhanced affinity of bNAbs to various HIV-1 envelope glycoproteins and non-HIV antigens. Binding adaptation of polyreactive bNAbs to the divergent ligands mainly involves hydrophophic interactions. Plasticity of bNAbs’ paratopes may, therefore, facilitate accommodating divergent viral variants, but it simultaneously triggers promiscuous binding to non-HIV-1 antigens. Thus, a certain level of polyreactivity can be a mark of adaptable antibodies displaying optimal pathogens’ recognition.
    Keywords antibody ; B cells ; HIV-1 ; polyreactivity ; autoreactivity ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2018-05-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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    Inter-library loan at ZB MED

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  6. Article ; Online: Diverse effects of interferon alpha on the establishment and reversal of HIV latency.

    Renée M Van der Sluis / Jennifer M Zerbato / Jake W Rhodes / Rachel D Pascoe / Ajantha Solomon / Nitasha A Kumar / Ashanti I Dantanarayana / Surekha Tennakoon / Jérémy Dufloo / James McMahon / Judy J Chang / Vanessa A Evans / Paul J Hertzog / Martin R Jakobsen / Andrew N Harman / Sharon R Lewin / Paul U Cameron

    PLoS Pathogens, Vol 16, Iss 2, p e

    2020  Volume 1008151

    Abstract: HIV latency is the major barrier to a cure for people living with HIV (PLWH) on antiretroviral therapy (ART) because the virus persists in long-lived non-proliferating and proliferating latently infected CD4+ T cells. Latently infected CD4+ T cells do ... ...

    Abstract HIV latency is the major barrier to a cure for people living with HIV (PLWH) on antiretroviral therapy (ART) because the virus persists in long-lived non-proliferating and proliferating latently infected CD4+ T cells. Latently infected CD4+ T cells do not express viral proteins and are therefore not visible to immune mediated clearance. Therefore, identifying interventions that can reverse latency and also enhance immune mediated clearance is of high interest. Interferons (IFNs) have multiple immune enhancing effects and can inhibit HIV replication in activated CD4+ T cells. However, the effects of IFNs on the establishment and reversal of HIV latency is not understood. Using an in vitro model of latency, we demonstrated that plasmacytoid dendritic cells (pDC) inhibit the establishment of HIV latency through secretion of type I IFNα, IFNβ and IFNω but not IFNε or type III IFNλ1 and IFNλ3. However, once latency was established, IFNα but no other IFNs were able to efficiently reverse latency in both an in vitro model of latency and CD4+ T cells collected from PLWH on suppressive ART. Binding of IFNα to its receptor expressed on primary CD4+ T cells did not induce activation of the canonical or non-canonical NFκB pathway but did induce phosphorylation of STAT1, 3 and 5 proteins. STAT5 has been previously demonstrated to bind to the HIV long terminal repeat and activate HIV transcription. We demonstrate diverse effects of interferons on HIV latency with type I IFNα; inhibiting the establishment of latency but also reversing HIV latency once latency is established.
    Keywords Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
    Subject code 570
    Language English
    Publishing date 2020-02-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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