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  1. Article ; Online: B cell somatic hypermutation following COVID-19 vaccination with Ad26.COV2.S.

    Jacob-Dolan, Catherine / Lifton, Michelle / Powers, Olivia C / Miller, Jessica / Hachmann, Nicole P / Vu, Mya / Surve, Nehalee / Mazurek, Camille R / Fisher, Jana L / Rodrigues, Stefanie / Patio, Robert C / Anand, Trisha / Le Gars, Mathieu / Sadoff, Jerald / Schmidt, Aaron G / Barouch, Dan H

    iScience

    2024  Volume 27, Issue 5, Page(s) 109716

    Abstract: The viral vector-based COVID-19 vaccine Ad26.COV2.S has been recommended by the WHO since 2021 and has been administered to over 200 million people. Prior studies have shown that Ad26.COV2.S induces durable neutralizing antibodies (NAbs) that increase in ...

    Abstract The viral vector-based COVID-19 vaccine Ad26.COV2.S has been recommended by the WHO since 2021 and has been administered to over 200 million people. Prior studies have shown that Ad26.COV2.S induces durable neutralizing antibodies (NAbs) that increase in coverage of variants over time, even in the absence of boosting or infection. Here, we studied humoral responses following Ad26.COV2.S vaccination in individuals enrolled in the initial Phase 1/2a trial of Ad26.COV2.S in 2020. Through 8 months post vaccination, serum NAb responses increased to variants, including B.1.351 (Beta) and B.1.617.2 (Delta), without additional boosting or infection. The level of somatic hypermutation, measured by nucleotide changes in the VDJ region of the heavy and light antibody chains, increased in Spike-specific B cells. Highly mutated mAbs from these sequences neutralized more SARS-CoV-2 variants than less mutated comparators. These findings suggest that the increase in NAb breadth over time following Ad26.COV2.S vaccination is mediated by affinity maturation.
    Language English
    Publishing date 2024-04-09
    Publishing country United States
    Document type Journal Article
    ISSN 2589-0042
    ISSN (online) 2589-0042
    DOI 10.1016/j.isci.2024.109716
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Waning immunity and IgG4 responses following bivalent mRNA boosting.

    Lasrado, Ninaad / Collier, Ai-Ris Y / Miller, Jessica / Hachmann, Nicole P / Liu, Jinyan / Anand, Trisha / A Bondzie, Esther / Fisher, Jana L / Mazurek, Camille R / Patio, Robert C / Rodrigues, Stefanie L / Rowe, Marjorie / Surve, Nehalee / Ty, Darren M / Wu, Cindy / Chicz, Taras M / Tong, Xin / Korber, Bette / McNamara, Ryan P /
    Barouch, Dan H

    Science advances

    2024  Volume 10, Issue 8, Page(s) eadj9945

    Abstract: Messenger RNA (mRNA) vaccines were highly effective against the ancestral SARS-CoV-2 strain, but the efficacy of bivalent mRNA boosters against XBB variants was substantially lower. Here, we show limited durability of neutralizing antibody (NAb) ... ...

    Abstract Messenger RNA (mRNA) vaccines were highly effective against the ancestral SARS-CoV-2 strain, but the efficacy of bivalent mRNA boosters against XBB variants was substantially lower. Here, we show limited durability of neutralizing antibody (NAb) responses against XBB variants and isotype switching to immunoglobulin G4 (IgG4) responses following bivalent mRNA boosting. Bivalent mRNA boosting elicited modest XBB.1-, XBB.1.5-, and XBB.1.16-specific NAbs that waned rapidly within 3 months. In contrast, bivalent mRNA boosting induced more robust and sustained NAbs against the ancestral WA1/2020 strain, suggesting immune imprinting. Following bivalent mRNA boosting, serum antibody responses were primarily IgG2 and IgG4 responses with poor Fc functional activity. In contrast, a third monovalent mRNA immunization boosted all isotypes including IgG1 and IgG3 with robust Fc functional activity. These data show substantial immune imprinting for the ancestral spike and isotype switching to IgG4 responses following bivalent mRNA boosting, with important implications for future booster designs and boosting strategies.
    MeSH term(s) Antibody Formation ; Immunoglobulin G ; Antibodies, Neutralizing ; Immunization ; RNA, Messenger/genetics ; mRNA Vaccines
    Chemical Substances Immunoglobulin G ; Antibodies, Neutralizing ; RNA, Messenger ; mRNA Vaccines
    Language English
    Publishing date 2024-02-23
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2810933-8
    ISSN 2375-2548 ; 2375-2548
    ISSN (online) 2375-2548
    ISSN 2375-2548
    DOI 10.1126/sciadv.adj9945
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Waning Immunity Against XBB.1.5 Following Bivalent mRNA Boosters.

    Lasrado, Ninaad / Collier, Ai-Ris Y / Miller, Jessica / Hachmann, Nicole P / Liu, Jinyan / Sciacca, Michaela / Wu, Cindy / Anand, Trisha / Bondzie, Esther A / Fisher, Jana L / Mazurek, Camille R / Patio, Robert C / Powers, Olivia / Rodrigues, Stefanie L / Rowe, Marjorie / Surve, Nehalee / Ty, Darren M / Korber, Bette / Barouch, Dan H

    bioRxiv : the preprint server for biology

    2023  

    Abstract: The SARS-CoV-2 Omicron variant has continued to evolve. XBB is a recombinant between two BA.2 sublineages, XBB.1 includes the G252V mutation, and XBB.1.5 includes the G252V and F486P mutations. XBB.1.5 has rapidly increased in frequency and has become ... ...

    Abstract The SARS-CoV-2 Omicron variant has continued to evolve. XBB is a recombinant between two BA.2 sublineages, XBB.1 includes the G252V mutation, and XBB.1.5 includes the G252V and F486P mutations. XBB.1.5 has rapidly increased in frequency and has become the dominant virus in New England. The bivalent mRNA vaccine boosters have been shown to increase neutralizing antibody (NAb) titers to multiple variants, but the durability of these responses remains to be determined. We assessed humoral and cellular immune responses in 30 participants who received the bivalent mRNA boosters and performed assays at baseline prior to boosting, at week 3 after boosting, and at month 3 after boosting. Our data demonstrate that XBB.1.5 substantially escapes NAb responses but not T cell responses after bivalent mRNA boosting. NAb titers to XBB.1 and XBB.1.5 were similar, suggesting that the F486P mutation confers greater transmissibility but not increased immune escape. By month 3, NAb titers to XBB.1 and XBB.1.5 declined essentially to baseline levels prior to boosting, while NAb titers to other variants declined less strikingly.
    Language English
    Publishing date 2023-01-23
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.01.22.525079
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Inter-library loan at ZB MED

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