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  1. Article ; Online: The Prevention of Inflammation and the Maintenance of Iron and Hepcidin Homeostasis in the Gut, Liver, and Brain Pathologies.

    Kania, Barbara / Sotelo, Alexis / Ty, Darren / Wisco, Jonathan J

    Journal of Alzheimer's disease : JAD

    2023  Volume 92, Issue 3, Page(s) 769–789

    Abstract: The human gut microbiome consists of a variety of microorganisms that inhabit the intestinal tract. This flora has recently been shown to play an important role in human disease. The crosstalk between the gut and brain axis has been investigated through ... ...

    Abstract The human gut microbiome consists of a variety of microorganisms that inhabit the intestinal tract. This flora has recently been shown to play an important role in human disease. The crosstalk between the gut and brain axis has been investigated through hepcidin, derived from both hepatocytes and dendritic cells. Hepcidin could potentially play an anti-inflammatory role in the process of gut dysbiosis through a means of either a localized approach of nutritional immunity, or a systemic approach. Like hepcidin, mBDNF and IL-6 are part of the gut-brain axis: gut microbiota affects their levels of expression, and this relationship is thought to play a role in cognitive function and decline, which could ultimately lead to a number of neurodegenerative diseases such as Alzheimer's disease. This review will focus on the interplay between gut dysbiosis and the crosstalk between the gut, liver, and brain and how this is mediated by hepcidin through different mechanisms including the vagus nerve and several different biomolecules. This overview will also focus on the gut microbiota-induced dysbiotic state on a systemic level, and how gut dysbiosis can contribute to beginnings and the progression of Alzheimer's disease and neuroinflammation.
    MeSH term(s) Humans ; Alzheimer Disease/metabolism ; Dysbiosis/metabolism ; Hepcidins/metabolism ; Iron/metabolism ; Inflammation/metabolism ; Liver/metabolism ; Brain/metabolism ; Homeostasis
    Chemical Substances Hepcidins ; Iron (E1UOL152H7)
    Language English
    Publishing date 2023-03-10
    Publishing country Netherlands
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 1440127-7
    ISSN 1875-8908 ; 1387-2877
    ISSN (online) 1875-8908
    ISSN 1387-2877
    DOI 10.3233/JAD-220224
    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 ; Online: Comparison of the immunogenicity and protective efficacy of ACAM2000, MVA, and vectored subunit vaccines for Mpox in rhesus macaques.

    Jacob-Dolan, Catherine / Ty, Darren / Hope, David / McMahan, Katherine / Liu, Jinyan / Powers, Olivia C / Cotter, Catherine A / Sciacca, Michela / Wu, Cindy / Borducchi, Erica / Bouffard, Emily / Richter, Hannah / Velasco, Jason / Teow, Elyse / Boursiquot, Mona / Cook, Anthony / Feliciano, Karen / Yalley-Ogunro, Jake / Seaman, Michael S /
    Pessiant, Laurent / Lewis, Mark G / Andersen, Hanne / Moss, Bernard / Barouch, Dan H

    Science translational medicine

    2024  Volume 16, Issue 740, Page(s) eadl4317

    Abstract: The 2022-2023 mpox outbreak triggered vaccination efforts using smallpox vaccines that were approved for mpox, including modified vaccinia Ankara (MVA; JYNNEOS), which is a safer alternative to live replicating vaccinia virus (ACAM2000). Here, we compare ...

    Abstract The 2022-2023 mpox outbreak triggered vaccination efforts using smallpox vaccines that were approved for mpox, including modified vaccinia Ankara (MVA; JYNNEOS), which is a safer alternative to live replicating vaccinia virus (ACAM2000). Here, we compare the immunogenicity and protective efficacy of JYNNEOS by the subcutaneous or intradermal routes, ACAM2000 by the percutaneous route, and subunit Ad35 vector-based L1R/B5R or L1R/B5R/A27L/A33R vaccines by the intramuscular route in rhesus macaques. All vaccines provided robust protection against high-dose intravenous mpox virus challenge with the current outbreak strain, with ACAM2000 providing near complete protection and JYNNEOS and Ad35 vaccines providing robust but incomplete protection. Protection correlated with neutralizing antibody responses as well as L1R/M1R- and B5R/B6R-specific binding antibody responses, although additional immune responses likely also contributed to protection. This study demonstrates the protective efficacy of multiple vaccine platforms against mpox virus challenge, including both current clinical vaccines and vectored subunit vaccines.
    MeSH term(s) Animals ; Vaccinia virus/genetics ; Macaca mulatta ; Mpox (monkeypox) ; Antibodies, Viral ; Smallpox Vaccine ; Vaccines, Subunit
    Chemical Substances ACAM2000 ; Antibodies, Viral ; Smallpox Vaccine ; Vaccines, Subunit
    Language English
    Publishing date 2024-03-27
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2518854-9
    ISSN 1946-6242 ; 1946-6234
    ISSN (online) 1946-6242
    ISSN 1946-6234
    DOI 10.1126/scitranslmed.adl4317
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. 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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  5. Article ; Online: Waning Immunity Against XBB.1.5 Following Bivalent mRNA Boosters

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

    bioRxiv

    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.
    Keywords covid19
    Language English
    Publishing date 2023-01-23
    Publisher Cold Spring Harbor Laboratory
    Document type Article ; Online
    DOI 10.1101/2023.01.22.525079
    Database COVID19

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