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  1. Article ; Online: Heterologous ChAdOx1 nCoV-19 and BNT162b2 prime-boost vaccination elicits potent neutralizing antibody responses and T cell reactivity against prevalent SARS-CoV-2 variants

    Rüdiger Groß / Michelle Zanoni / Alina Seidel / Carina Conzelmann / Andrea Gilg / Daniela Krnavek / Sümeyye Erdemci-Evin / Benjamin Mayer / Markus Hoffmann / Stefan Pöhlmann / Weimin Liu / Beatrice H. Hahn / Alexandra Beil / Joris Kroschel / Bernd Jahrsdörfer / Hubert Schrezenmeier / Frank Kirchhoff / Jan Münch / Janis A. Müller

    EBioMedicine, Vol 75, Iss , Pp 103761- (2022)

    2022  

    Abstract: Summary: Background: Heterologous COVID-19 vaccination regimens combining vector- and mRNA-based vaccines are already administered, but data on solicited adverse reactions, immunological responses and elicited protection are limited. Methods: To evaluate ...

    Abstract Summary: Background: Heterologous COVID-19 vaccination regimens combining vector- and mRNA-based vaccines are already administered, but data on solicited adverse reactions, immunological responses and elicited protection are limited. Methods: To evaluate the reactogenicity and humoral as well as cellular immune responses towards most prevalent SARS-CoV-2 variants after a heterologous ChAdOx1 nCoV-19 BNT162b2 prime-boost vaccination, we analysed a cohort of 26 clinic employees aged 25-46 (median 30.5) years who received a ChAdOx1 nCoV-19 prime followed by a BNT162b2 boost after an 8-week interval. Serological data were compared to a cohort which received homologous BNT162b2 vaccination with a 3-week interval (14 individuals aged 25-65, median 42). Findings: Self-reported solicited symptoms after ChAdOx1 nCoV-19 prime were in line with previous reports and more severe than after the BNT162b2 boost. Antibody titres increased significantly over time resulting in strong neutralization titres two weeks after the BNT162b2 boost and subsequently slightly decreased over the course of 17 weeks. At the latest time point measured, all analysed sera retained neutralizing activity against the currently dominant Delta (B.1.617.2) variant. Two weeks post boost, neutralizing activity against the Alpha (B.1.1.7) and immune-evading Beta (B.1.351) variant was ∼4-fold higher than in individuals receiving homologous BNT162b2 vaccination. No difference was observed in neutralization of Kappa (B.1.617.1). In addition, heterologous vaccination induced CD4+ and CD8+ T cells reactive to SARS-CoV-2 spike peptides of all analysed variants; Wuhan-Hu-1, Alpha, Beta, Gamma (P.1), and Delta. Interpretation: In conclusion, heterologous ChAdOx1 nCoV-19 / BNT162b2 prime-boost vaccination is not associated with serious adverse events and induces potent humoral and cellular immune responses. The Alpha, Beta, Delta, and Kappa variants of spike are potently neutralized by sera from all participants and reactive T cells recognize spike peptides of all ...
    Keywords COVID-19 ; Delta ; B.1.617.2 ; immunity ; heterologous vaccination ; Medicine ; R ; Medicine (General) ; R5-920
    Subject code 796
    Language English
    Publishing date 2022-01-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Uniquely altered transcripts are associated with immune preservation in HIV infection.

    Michelle Zanoni / Ítalo Karmann Aventurato / James Hunter / Maria Cecilia Araripe Sucupira / Ricardo Sobhie Diaz

    PLoS ONE, Vol 12, Iss 3, p e

    2017  Volume 0169868

    Abstract: The mechanisms underlying host HIV control hold much promise in the search for a functional HIV cure. We investigated the host genomic signatures in elite controllers or rapid progressors following recent infection and the correlates of immune ... ...

    Abstract The mechanisms underlying host HIV control hold much promise in the search for a functional HIV cure. We investigated the host genomic signatures in elite controllers or rapid progressors following recent infection and the correlates of immune reconstitution during combination antiretroviral therapy. We characterized the HIV-specific longitudinal host transcriptional response of peripheral blood mononuclear cells from elite controllers, rapid progressors, immune responders and non-responders using a RT-qPCR array in a cohort of recently HIV-infected Brazilian individuals. The elite controllers expressed unique transcripts early in infection that were closely associated with specialized cross-presentation between XCR1+ DCs and antigen-specific CD8+ T cells (XCL1). The natural suppression of HIV was also associated with the highly functional co-expression of cytokines and chemokines (CCL2, TNF and IL-10) concomitant with the maintenance of important anti-inflammatory and anticoagulant properties (Antithrombin III). Immune responders exhibited exclusively upregulated mRNAs possibly related to stem cell mobilization before combination antiretroviral therapy (neutrophil elastase). Our longitudinal approach to gene expression permitted us to discover previously unrecognized determinants that contribute to natural or antiretroviral-mediated HIV-1 immune control.
    Keywords Medicine ; R ; Science ; Q
    Subject code 570
    Language English
    Publishing date 2017-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Innate, non-cytolytic CD8+ T cell-mediated suppression of HIV replication by MHC-independent inhibition of virus transcription.

    Michelle Zanoni / David Palesch / Claudia Pinacchio / Maura Statzu / Gregory K Tharp / Mirko Paiardini / Ann Chahroudi / Steven E Bosinger / Jack Yoon / Bryan Cox / Guido Silvestri / Deanna A Kulpa

    PLoS Pathogens, Vol 16, Iss 9, p e

    2020  Volume 1008821

    Abstract: MHC-I-restricted, virus-specific cytotoxic CD8+ T cells (CTLs) may control human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) replication via the recognition and killing of productively infected CD4+ T cells. Several studies in ... ...

    Abstract MHC-I-restricted, virus-specific cytotoxic CD8+ T cells (CTLs) may control human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) replication via the recognition and killing of productively infected CD4+ T cells. Several studies in SIV-infected macaques suggest that CD8+ T cells may also decrease virus production by suppressing viral transcription. Here, we show that non-HIV-specific, TCR-activated non-cytolytic CD8+ T cells suppress HIV transcription via a virus- and MHC-independent immunoregulatory mechanism that modulates CD4+ T cell proliferation and activation. We also demonstrate that this CD8+ T cell-mediated effect promotes the survival of infected CD4+ T cells harboring integrated, inducible virus. Finally, we used RNA sequencing and secretome analyses to identify candidate cellular pathways that are involved in the virus-silencing mediated by these CD8+ T cells. This study characterizes a previously undescribed mechanism of immune-mediated HIV silencing that may be involved in the establishment and maintenance of the reservoir under antiretroviral therapy and therefore represent a major obstacle to HIV eradication.
    Keywords Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
    Subject code 570
    Language English
    Publishing date 2020-09-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Correction

    Bruno Scarpellini / Michelle Zanoni / Maria Cecilia Araripe Sucupira / Hong-Ha M Truong / Luiz Mario Ramos Janini / Ismael Dale da Silva / Ricardo Sobhie Diaz

    PLoS ONE, Vol 12, Iss 2, p e

    Plasma Metabolomics Biosignature According to HIV Stage of Infection, Pace of Disease Progression, Viremia Level and Immunological Response to Treatment.

    2017  Volume 0173164

    Abstract: This corrects the article DOI:10.1371/journal.pone.0161920.]. ...

    Abstract [This corrects the article DOI:10.1371/journal.pone.0161920.].
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2017-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  5. Article ; Online: Plasma Metabolomics Biosignature According to HIV Stage of Infection, Pace of Disease Progression, Viremia Level and Immunological Response to Treatment.

    Bruno Scarpellini / Michelle Zanoni / Maria Cecilia Araripe Sucupira / Hong-Ha M Truong / Luiz Mario Ramos Janini / Ismael Dale Cotrin Segurado / Ricardo Sobhie Diaz

    PLoS ONE, Vol 11, Iss 12, p e

    2016  Volume 0161920

    Abstract: We evaluated plasma samples HIV-infected individuals with different phenotypic profile among five HIV-infected elite controllers and five rapid progressors after recent HIV infection and one year later and from 10 individuals subjected to antiretroviral ... ...

    Abstract We evaluated plasma samples HIV-infected individuals with different phenotypic profile among five HIV-infected elite controllers and five rapid progressors after recent HIV infection and one year later and from 10 individuals subjected to antiretroviral therapy, five of whom were immunological non-responders (INR), before and after one year of antiretroviral treatment compared to 175 samples from HIV-negative patients. A targeted quantitative tandem mass spectrometry metabolomics approach was used in order to determine plasma metabolomics biosignature that may relate to HIV infection, pace of HIV disease progression, and immunological response to treatment.Twenty-five unique metabolites were identified, including five metabolites that could distinguish rapid progressors and INRs at baseline. Severe deregulation in acylcarnitine and sphingomyelin metabolism compatible with mitochondrial deficiencies was observed. β-oxidation and sphingosine-1-phosphate-phosphatase-1 activity were down-regulated, whereas acyl-alkyl-containing phosphatidylcholines and alkylglyceronephosphate synthase levels were elevated in INRs. Evidence that elite controllers harbor an inborn error of metabolism (late-onset multiple acyl-coenzyme A dehydrogenase deficiency [MADD]) was detected.Blood-based markers from metabolomics show a very high accuracy of discriminating HIV infection between varieties of controls and have the ability to predict rapid disease progression or poor antiretroviral immunological response. These metabolites can be used as biomarkers of HIV natural evolution or treatment response and provide insight into the mechanisms of the disease.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2016-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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    Inter-library loan at ZB MED

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