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  1. Artikel: T-cell mediated immunity after AZD1222 vaccination: A polyfunctional spike-specific Th1 response with a diverse TCR repertoire.

    Swanson, Phillip A / Padilla, Marcelino / Hoyland, Wesley / McGlinchey, Kelly / Fields, Paul A / Bibi, Sagida / Faust, Saul N / McDermott, Adrian B / Lambe, Teresa / Pollard, Andrew J / Durham, Nicholas M / Kelly, Elizabeth J

    medRxiv : the preprint server for health sciences

    2021  

    Abstract: AZD1222 (ChAdOx1 nCoV-19), a replication-deficient simian adenovirus-vectored vaccine, has demonstrated safety, efficacy, and immunogenicity against coronavirus disease 2019 (COVID-19) in clinical trials and real-world studies. We characterized CD4+ and ... ...

    Abstract AZD1222 (ChAdOx1 nCoV-19), a replication-deficient simian adenovirus-vectored vaccine, has demonstrated safety, efficacy, and immunogenicity against coronavirus disease 2019 (COVID-19) in clinical trials and real-world studies. We characterized CD4+ and CD8+ T-cell responses induced by AZD1222 vaccination in peripheral blood mononuclear cells (PBMCs) from 280 unique vaccine recipients aged 18-85 years who enrolled in the phase 2/3 COV002 trial. Total spike-specific CD4+ T cell helper type 1 (Th1) and CD8+ T-cell responses were significantly increased in AZD1222-vaccinated adults of all ages following two doses of AZD1222. CD4+ Th2 responses following AZD1222 vaccination were not detected. Furthermore, AZD1222-specific Th1 and CD8+ T cells both displayed a high degree of polyfunctionality in all adult age groups. T-cell receptor (TCR) β sequences from vaccinated participants mapped against TCR sequences known to react to SARS-CoV-2 revealed substantial breadth and depth across the SARS-CoV-2 spike protein for the AZD1222-induced CD4+ and CD8+ T-cell responses. Overall, AZD1222 vaccination induced a robust, polyfunctional Th1-dominated T-cell response, with broad CD4+ and CD8+ T-cell coverage across the SARS-CoV-2 spike protein.
    One sentence summary: Polyfunctional CD4+ and CD8+ T-cell responses are elicited against the SARS-CoV-2 spike protein following vaccination with AZD1222.
    Sprache Englisch
    Erscheinungsdatum 2021-07-13
    Erscheinungsland United States
    Dokumenttyp Preprint
    DOI 10.1101/2021.06.17.21259027
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: AZD1222/ChAdOx1 nCoV-19 vaccination induces a polyfunctional spike protein-specific T

    Swanson, Phillip A / Padilla, Marcelino / Hoyland, Wesley / McGlinchey, Kelly / Fields, Paul A / Bibi, Sagida / Faust, Saul N / McDermott, Adrian B / Lambe, Teresa / Pollard, Andrew J / Durham, Nicholas M / Kelly, Elizabeth J

    Science translational medicine

    2021  Band 13, Heft 620, Seite(n) eabj7211

    Abstract: AZD1222 (ChAdOx1 nCoV-19), a replication-deficient simian adenovirus–vectored vaccine, has demonstrated safety, efficacy, and immunogenicity against coronavirus disease 2019 in clinical trials and real-world studies. We characterized ... ...

    Abstract AZD1222 (ChAdOx1 nCoV-19), a replication-deficient simian adenovirus–vectored vaccine, has demonstrated safety, efficacy, and immunogenicity against coronavirus disease 2019 in clinical trials and real-world studies. We characterized CD4
    Mesh-Begriff(e) COVID-19 ; COVID-19 Vaccines ; ChAdOx1 nCoV-19 ; Humans ; Receptors, Antigen, T-Cell ; SARS-CoV-2 ; Spike Glycoprotein, Coronavirus ; Vaccination
    Chemische Substanzen COVID-19 Vaccines ; Receptors, Antigen, T-Cell ; Spike Glycoprotein, Coronavirus ; ChAdOx1 nCoV-19 (B5S3K2V0G8)
    Sprache Englisch
    Erscheinungsdatum 2021-11-17
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2518854-9
    ISSN 1946-6242 ; 1946-6234
    ISSN (online) 1946-6242
    ISSN 1946-6234
    DOI 10.1126/scitranslmed.abj7211
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel ; Online: T-cell mediated immunity after AZD1222 vaccination: A polyfunctional spike-specific Th1 response with a diverse TCR repertoire

    Swanson, Phillip A. / Padilla, Marcelino / Hoyland, Wesley / McGlinchey, Kelly / Fields, Paul A. / Bibi, Sagida / Faust, Saul N. / McDermott, Adrian B. / Lambe, Teresa / Pollard, Andrew J. / Durham, Nicholas M. / Kelly, Elizabeth J. / Study Group

    medRxiv

    Abstract: AZD1222 (ChAdOx1 nCoV-19), a replication-deficient simian adenovirus-vectored vaccine, has demonstrated safety, efficacy, and immunogenicity against coronavirus disease 2019 (COVID-19) in clinical trials and real-world studies. We characterized CD4+ and ... ...

    Abstract AZD1222 (ChAdOx1 nCoV-19), a replication-deficient simian adenovirus-vectored vaccine, has demonstrated safety, efficacy, and immunogenicity against coronavirus disease 2019 (COVID-19) in clinical trials and real-world studies. We characterized CD4+ and CD8+ T-cell responses induced by AZD1222 vaccination in peripheral blood mononuclear cells (PBMCs) from 280 unique vaccine recipients aged 18-85 years who enrolled in the phase 2/3 COV002 trial. Total spike-specific CD4+ T cell helper type 1 (Th1) and CD8+ T-cell responses were significantly increased in AZD1222-vaccinated adults of all ages following two doses of AZD1222. CD4+ Th2 responses following AZD1222 vaccination were not detected. Furthermore, AZD1222-specific Th1 and CD8+ T cells both displayed a high degree of polyfunctionality in all adult age groups. T-cell receptor (TCR) β

    sequences from vaccinated participants mapped against TCR sequences known to react to SARS-CoV-2 revealed substantial breadth and depth across the SARS-CoV-2 spike protein for the AZD1222-induced CD4+ and CD8+ T-cell responses. Overall, AZD1222 vaccination induced a robust, polyfunctional Th1-dominated T-cell response, with broad CD4+ and CD8+ T-cell coverage across the SARS-CoV-2 spike protein.
    Schlagwörter covid19
    Sprache Englisch
    Erscheinungsdatum 2021-06-23
    Verlag Cold Spring Harbor Laboratory Press
    Dokumenttyp Artikel ; Online
    DOI 10.1101/2021.06.17.21259027
    Datenquelle COVID19

    Volltext online

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  4. Artikel ; Online: Human immunoglobulin gene allelic variation impacts germline-targeting vaccine priming.

    deCamp, Allan C / Corcoran, Martin M / Fulp, William J / Willis, Jordan R / Cottrell, Christopher A / Bader, Daniel L V / Kalyuzhniy, Oleksandr / Leggat, David J / Cohen, Kristen W / Hyrien, Ollivier / Menis, Sergey / Finak, Greg / Ballweber-Fleming, Lamar / Srikanth, Abhinaya / Plyler, Jason R / Rahaman, Farhad / Lombardo, Angela / Philiponis, Vincent / Whaley, Rachael E /
    Seese, Aaron / Brand, Joshua / Ruppel, Alexis M / Hoyland, Wesley / Mahoney, Celia R / Cagigi, Alberto / Taylor, Alison / Brown, David M / Ambrozak, David R / Sincomb, Troy / Mullen, Tina-Marie / Maenza, Janine / Kolokythas, Orpheus / Khati, Nadia / Bethony, Jeffrey / Roederer, Mario / Diemert, David / Koup, Richard A / Laufer, Dagna S / McElrath, Juliana M / McDermott, Adrian B / Karlsson Hedestam, Gunilla B / Schief, William R

    NPJ vaccines

    2024  Band 9, Heft 1, Seite(n) 58

    Abstract: Vaccine priming immunogens that activate germline precursors for broadly neutralizing antibodies (bnAbs) have promise for development of precision vaccines against major human pathogens. In a clinical trial of the eOD-GT8 60mer germline-targeting ... ...

    Abstract Vaccine priming immunogens that activate germline precursors for broadly neutralizing antibodies (bnAbs) have promise for development of precision vaccines against major human pathogens. In a clinical trial of the eOD-GT8 60mer germline-targeting immunogen, higher frequencies of vaccine-induced VRC01-class bnAb-precursor B cells were observed in the high dose compared to the low dose group. Through immunoglobulin heavy chain variable (IGHV) genotyping, statistical modeling, quantification of IGHV1-2 allele usage and B cell frequencies in the naive repertoire for each trial participant, and antibody affinity analyses, we found that the difference between dose groups in VRC01-class response frequency was best explained by IGHV1-2 genotype rather than dose and was most likely due to differences in IGHV1-2 B cell frequencies for different genotypes. The results demonstrate the need to define population-level immunoglobulin allelic variations when designing germline-targeting immunogens and evaluating them in clinical trials.
    Sprache Englisch
    Erscheinungsdatum 2024-03-11
    Erscheinungsland England
    Dokumenttyp Journal Article
    ISSN 2059-0105
    ISSN (online) 2059-0105
    DOI 10.1038/s41541-024-00811-5
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  5. Artikel ; Online: Recombinant MVA-prime elicits neutralizing antibody responses by inducing antigen-specific B cells in the germinal center.

    Eslamizar, Leila / Petrovas, Constantinos / Leggat, David J / Furr, Kathryn / Lifton, Michelle L / Levine, Gail / Ma, Steven / Fletez-Brant, Christopher / Hoyland, Wesley / Prabhakaran, Madhu / Narpala, Sandeep / Boswell, Kristin / Yamamoto, Takuya / Liao, Hua-Xin / Pickup, David / Ramsburg, Elizabeth / Sutherland, Laura / McDermott, Adrian / Roederer, Mario /
    Montefiori, David / Koup, Richard A / Haynes, Barton F / Letvin, Norman L / Santra, Sampa

    NPJ vaccines

    2021  Band 6, Heft 1, Seite(n) 15

    Abstract: The RV144 HIV-1 vaccine trial has been the only clinical trial to date that has shown any degree of efficacy and associated with the presence of vaccine-elicited HIV-1 envelope-specific binding antibody and CD4+ T-cell responses. This trial also showed ... ...

    Abstract The RV144 HIV-1 vaccine trial has been the only clinical trial to date that has shown any degree of efficacy and associated with the presence of vaccine-elicited HIV-1 envelope-specific binding antibody and CD4+ T-cell responses. This trial also showed that a vector-prime protein boost combined vaccine strategy was better than when used alone. Here we have studied three different priming vectors-plasmid DNA, recombinant MVA, and recombinant VSV, all encoding clade C transmitted/founder Env 1086 C gp140, for priming three groups of six non-human primates each, followed by a protein boost with adjuvanted 1086 C gp120 protein. Our data showed that MVA-priming favors the development of higher antibody binding titers and neutralizing activity compared with other vectors. Analyses of the draining lymph nodes revealed that MVA-prime induced increased germinal center reactivity characterized by higher frequencies of germinal center (PNA
    Sprache Englisch
    Erscheinungsdatum 2021-01-25
    Erscheinungsland England
    Dokumenttyp Journal Article
    ISSN 2059-0105
    ISSN (online) 2059-0105
    DOI 10.1038/s41541-020-00277-1
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  6. Artikel: Human immunoglobulin gene allelic variation impacts germline-targeting vaccine priming.

    deCamp, Allan C / Corcoran, Martin M / Fulp, William J / Willis, Jordan R / Cottrell, Christopher A / Bader, Daniel L V / Kalyuzhniy, Oleksandr / Leggat, David J / Cohen, Kristen W / Hyrien, Ollivier / Menis, Sergey / Finak, Greg / Ballweber-Fleming, Lamar / Srikanth, Abhinaya / Plyler, Jason R / Rahaman, Farhad / Lombardo, Angela / Philiponis, Vincent / Whaley, Rachael E /
    Seese, Aaron / Brand, Joshua / Ruppel, Alexis M / Hoyland, Wesley / Mahoney, Celia R / Cagigi, Alberto / Taylor, Alison / Brown, David M / Ambrozak, David R / Sincomb, Troy / Mullen, Tina-Marie / Maenza, Janine / Kolokythas, Orpheus / Khati, Nadia / Bethony, Jeffrey / Roederer, Mario / Diemert, David / Koup, Richard A / Laufer, Dagna S / McElrath, Juliana M / McDermott, Adrian B / Hedestam, Gunilla B Karlsson / Schief, William R

    medRxiv : the preprint server for health sciences

    2023  

    Abstract: Vaccine priming immunogens that activate germline precursors for broadly neutralizing antibodies (bnAbs) have promise for development of precision vaccines against major human pathogens. In a clinical trial of the eOD-GT8 60mer germline-targeting ... ...

    Abstract Vaccine priming immunogens that activate germline precursors for broadly neutralizing antibodies (bnAbs) have promise for development of precision vaccines against major human pathogens. In a clinical trial of the eOD-GT8 60mer germline-targeting immunogen, higher frequencies of vaccine-induced VRC01-class bnAb-precursor B cells were observed in the high dose compared to the low dose group. Through immunoglobulin heavy chain variable (IGHV) genotyping, statistical modeling, quantification of IGHV1-2 allele usage and B cell frequencies in the naive repertoire for each trial participant, and antibody affinity analyses, we found that the difference between dose groups in VRC01-class response frequency was best explained by IGHV1-2 genotype rather than dose and was most likely due to differences in IGHV1-2 B cell frequencies for different genotypes. The results demonstrate the need to define population-level immunoglobulin allelic variations when designing germline-targeting immunogens and evaluating them in clinical trials.
    One-sentence summary: Human genetic variation can modulate the strength of vaccine-induced broadly neutralizing antibody precursor B cell responses.
    Sprache Englisch
    Erscheinungsdatum 2023-03-15
    Erscheinungsland United States
    Dokumenttyp Preprint
    DOI 10.1101/2023.03.10.23287126
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  7. Artikel ; Online: Vaccination induces HIV broadly neutralizing antibody precursors in humans.

    Leggat, David J / Cohen, Kristen W / Willis, Jordan R / Fulp, William J / deCamp, Allan C / Kalyuzhniy, Oleksandr / Cottrell, Christopher A / Menis, Sergey / Finak, Greg / Ballweber-Fleming, Lamar / Srikanth, Abhinaya / Plyler, Jason R / Schiffner, Torben / Liguori, Alessia / Rahaman, Farhad / Lombardo, Angela / Philiponis, Vincent / Whaley, Rachael E / Seese, Aaron /
    Brand, Joshua / Ruppel, Alexis M / Hoyland, Wesley / Yates, Nicole L / Williams, LaTonya D / Greene, Kelli / Gao, Hongmei / Mahoney, Celia R / Corcoran, Martin M / Cagigi, Alberto / Taylor, Alison / Brown, David M / Ambrozak, David R / Sincomb, Troy / Hu, Xiaozhen / Tingle, Ryan / Georgeson, Erik / Eskandarzadeh, Saman / Alavi, Nushin / Lu, Danny / Mullen, Tina-Marie / Kubitz, Michael / Groschel, Bettina / Maenza, Janine / Kolokythas, Orpheus / Khati, Nadia / Bethony, Jeffrey / Crotty, Shane / Roederer, Mario / Karlsson Hedestam, Gunilla B / Tomaras, Georgia D / Montefiori, David / Diemert, David / Koup, Richard A / Laufer, Dagna S / McElrath, M Juliana / McDermott, Adrian B / Schief, William R

    Science (New York, N.Y.)

    2022  Band 378, Heft 6623, Seite(n) eadd6502

    Abstract: Broadly neutralizing antibodies (bnAbs) can protect against HIV infection but have not been induced by human vaccination. A key barrier to bnAb induction is vaccine priming of rare bnAb-precursor B cells. In a randomized, double-blind, placebo-controlled ...

    Abstract Broadly neutralizing antibodies (bnAbs) can protect against HIV infection but have not been induced by human vaccination. A key barrier to bnAb induction is vaccine priming of rare bnAb-precursor B cells. In a randomized, double-blind, placebo-controlled phase 1 clinical trial, the HIV vaccine-priming candidate eOD-GT8 60mer adjuvanted with AS01
    Mesh-Begriff(e) Humans ; Adjuvants, Immunologic ; AIDS Vaccines/immunology ; Broadly Neutralizing Antibodies/genetics ; Broadly Neutralizing Antibodies/immunology ; HIV Infections/prevention & control ; Vaccination ; HIV Antibodies/genetics ; HIV Antibodies/immunology ; Germ Cells/immunology ; B-Lymphocytes/immunology ; Mutation ; Immunoglobulin Light Chains/genetics ; Immunoglobulin Light Chains/immunology ; Immunoglobulin Heavy Chains/genetics ; Immunoglobulin Heavy Chains/immunology ; Male ; Female ; Adult
    Chemische Substanzen Adjuvants, Immunologic ; AIDS Vaccines ; Broadly Neutralizing Antibodies ; HIV Antibodies ; Immunoglobulin Light Chains ; Immunoglobulin Heavy Chains
    Sprache Englisch
    Erscheinungsdatum 2022-12-02
    Erscheinungsland United States
    Dokumenttyp Clinical Trial, Phase I ; Journal Article ; Randomized Controlled Trial ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 128410-1
    ISSN 1095-9203 ; 0036-8075
    ISSN (online) 1095-9203
    ISSN 0036-8075
    DOI 10.1126/science.add6502
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 27: Hefte anzeigen Standort:
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