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  1. Article ; Online: Diamino Allose Phosphates: Novel, Potent, and Highly Stable Toll-like Receptor 4 Agonists.

    Khalaf, Juhienah K / Bess, Laura S / Walsh, Lois M / Ward, Janine M / Johnson, Craig L / Livesay, Mark T / Jackson, Konner J / Evans, Jay T / Ryter, Kendal T / Bazin-Lee, Hélène G

    Journal of medicinal chemistry

    2023  Volume 66, Issue 20, Page(s) 13900–13917

    Abstract: Most known synthetic toll-like receptor 4 (TLR4) agonists are carbohydrate-based lipid-A mimetics containing several fatty acyl chains, including a labile 3- ...

    Abstract Most known synthetic toll-like receptor 4 (TLR4) agonists are carbohydrate-based lipid-A mimetics containing several fatty acyl chains, including a labile 3-
    MeSH term(s) Animals ; Mice ; Toll-Like Receptor 4 ; Adjuvants, Vaccine ; Immunologic Factors ; Adjuvants, Immunologic/pharmacology ; Adjuvants, Immunologic/chemistry ; Ligands ; Antibodies, Viral
    Chemical Substances Toll-Like Receptor 4 ; Adjuvants, Vaccine ; Immunologic Factors ; Adjuvants, Immunologic ; Ligands ; Antibodies, Viral
    Language English
    Publishing date 2023-10-17
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 218133-2
    ISSN 1520-4804 ; 0022-2623
    ISSN (online) 1520-4804
    ISSN 0022-2623
    DOI 10.1021/acs.jmedchem.3c00724
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.B 151: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)
    Zs.MB 1: Show issues

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  2. Article: Co-encapsulation of synthetic lipidated TLR4 and TLR7/8 agonists in the liposomal bilayer results in a rapid, synergistic enhancement of vaccine-mediated humoral immunity

    Short, Kristopher K / Miller, Shannon M / Walsh, Lois / Cybulski, Van / Bazin, Hélène / Evans, Jay T / Burkhart, David

    Elsevier B.V. Journal of controlled release. 2019 Dec. 10, v. 315

    2019  

    Abstract: To increase vaccine immunogenicity, modern vaccines incorporate adjuvants, which serve to enhance immune cross-protection, improve humoral and cell-mediated immunity, and promote antigen dose sparing. Pattern recognition receptors (PRRs), including the ... ...

    Abstract To increase vaccine immunogenicity, modern vaccines incorporate adjuvants, which serve to enhance immune cross-protection, improve humoral and cell-mediated immunity, and promote antigen dose sparing. Pattern recognition receptors (PRRs), including the Toll-like receptor (TLR) family are promising targets for development of agonist formulations for use as vaccine adjuvants. Combinations of co-delivered TLR4 and TLR7/8 ligands have been demonstrated to have synergistic effects on innate and adaptive immune response. Here, we create liposomes that stably co-encapsulate CRX-601, a synthetic TLR4 agonist, and UM-3004, a lipidated TLR7/8 agonist, within the liposomal bilayer in order to achieve co-delivery, allow tunable physical properties, and induce in vitro and in vivo immune synergy. Co-encapsulation demonstrates a synergistic increase in IL-12p70 cytokine output in vitro from treated human peripheral blood mononuclear cells (hPBMCs). Further, co-encapsulated formulations give significant improvement of early IgG2a antibody titers in BALB/c mice following primary vaccination when compared to single agonist or dual agonists delivered in separate liposomes. This work demonstrates that co-encapsulation of TLR4 and lipidated TLR7/8 agonists within the liposomal bilayer leads to innate and adaptive immune synergy which biases a Th1 immune response. Thus, liposomal co-encapsulation may be a useful and flexible tool for vaccine adjuvant formulation containing multiple TLR agonists.
    Keywords Toll-like receptor 4 ; Toll-like receptor 7 ; agonists ; antibodies ; antigens ; cell-mediated immunity ; cross immunity ; humans ; humoral immunity ; immune response ; immunogenicity ; immunoglobulin G ; interleukin-12 ; ligands ; mice ; mononuclear leukocytes ; physical properties ; synergism ; vaccination ; vaccine adjuvants ; vaccines
    Language English
    Dates of publication 2019-1210
    Size p. 186-196.
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 632533-6
    ISSN 1873-4995 ; 0168-3659
    ISSN (online) 1873-4995
    ISSN 0168-3659
    DOI 10.1016/j.jconrel.2019.10.025
    Database NAL-Catalogue (AGRICOLA)

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2055: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  3. Article ; Online: Co-encapsulation of synthetic lipidated TLR4 and TLR7/8 agonists in the liposomal bilayer results in a rapid, synergistic enhancement of vaccine-mediated humoral immunity.

    Short, Kristopher K / Miller, Shannon M / Walsh, Lois / Cybulski, Van / Bazin, Hélène / Evans, Jay T / Burkhart, David

    Journal of controlled release : official journal of the Controlled Release Society

    2019  Volume 315, Page(s) 186–196

    Abstract: To increase vaccine immunogenicity, modern vaccines incorporate adjuvants, which serve to enhance immune cross-protection, improve humoral and cell-mediated immunity, and promote antigen dose sparing. Pattern recognition receptors (PRRs), including the ... ...

    Abstract To increase vaccine immunogenicity, modern vaccines incorporate adjuvants, which serve to enhance immune cross-protection, improve humoral and cell-mediated immunity, and promote antigen dose sparing. Pattern recognition receptors (PRRs), including the Toll-like receptor (TLR) family are promising targets for development of agonist formulations for use as vaccine adjuvants. Combinations of co-delivered TLR4 and TLR7/8 ligands have been demonstrated to have synergistic effects on innate and adaptive immune response. Here, we create liposomes that stably co-encapsulate CRX-601, a synthetic TLR4 agonist, and UM-3004, a lipidated TLR7/8 agonist, within the liposomal bilayer in order to achieve co-delivery, allow tunable physical properties, and induce in vitro and in vivo immune synergy. Co-encapsulation demonstrates a synergistic increase in IL-12p70 cytokine output in vitro from treated human peripheral blood mononuclear cells (hPBMCs). Further, co-encapsulated formulations give significant improvement of early IgG2a antibody titers in BALB/c mice following primary vaccination when compared to single agonist or dual agonists delivered in separate liposomes. This work demonstrates that co-encapsulation of TLR4 and lipidated TLR7/8 agonists within the liposomal bilayer leads to innate and adaptive immune synergy which biases a Th1 immune response. Thus, liposomal co-encapsulation may be a useful and flexible tool for vaccine adjuvant formulation containing multiple TLR agonists.
    MeSH term(s) Adjuvants, Immunologic/administration & dosage ; Animals ; Drug Delivery Systems ; Drug Synergism ; Female ; Heterocyclic Compounds, 3-Ring/administration & dosage ; Heterocyclic Compounds, 3-Ring/immunology ; Heterocyclic Compounds, 3-Ring/pharmacology ; Humans ; Immunity, Humoral/immunology ; Leukocytes, Mononuclear/immunology ; Liposomes ; Mice ; Mice, Inbred BALB C ; Monosaccharides/administration & dosage ; Monosaccharides/immunology ; Monosaccharides/pharmacology ; Th1 Cells/immunology ; Toll-Like Receptor 4/agonists ; Toll-Like Receptor 7/agonists ; Toll-Like Receptor 8/agonists ; Vaccines/administration & dosage ; Vaccines/immunology
    Chemical Substances Adjuvants, Immunologic ; Heterocyclic Compounds, 3-Ring ; Liposomes ; Monosaccharides ; Toll-Like Receptor 4 ; Toll-Like Receptor 7 ; Toll-Like Receptor 8 ; Vaccines
    Language English
    Publishing date 2019-10-22
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 632533-6
    ISSN 1873-4995 ; 0168-3659
    ISSN (online) 1873-4995
    ISSN 0168-3659
    DOI 10.1016/j.jconrel.2019.10.025
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2055: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  4. Article ; Online: Novel Lipidated Imidazoquinoline TLR7/8 Adjuvants Elicit Influenza-Specific Th1 Immune Responses and Protect Against Heterologous H3N2 Influenza Challenge in Mice.

    Miller, Shannon M / Cybulski, Van / Whitacre, Margaret / Bess, Laura S / Livesay, Mark T / Walsh, Lois / Burkhart, David / Bazin, Hélène G / Evans, Jay T

    Frontiers in immunology

    2020  Volume 11, Page(s) 406

    Abstract: Most licensed seasonal influenza vaccines are non-adjuvanted and rely primarily on vaccine-induced antibody titers for protection. As such, seasonal antigenic drift and suboptimal vaccine strain selection often results in reduced vaccine efficacy. ... ...

    Abstract Most licensed seasonal influenza vaccines are non-adjuvanted and rely primarily on vaccine-induced antibody titers for protection. As such, seasonal antigenic drift and suboptimal vaccine strain selection often results in reduced vaccine efficacy. Further, seasonal H3N2 influenza vaccines demonstrate poor efficacy compared to H1N1 and influenza type B vaccines. New vaccines, adjuvants, or delivery technologies that can induce broader or cross-seasonal protection against drifted influenza virus strains, likely through induction of protective T cell responses, are urgently needed. Here, we report novel lipidated TLR7/8 ligands that act as strong adjuvants to promote influenza-virus specific Th1-and Th17-polarized T cell responses and humoral responses in mice with no observable toxicity. Further, the adjuvanted influenza vaccine provided protection against a heterologous H3N2 influenza challenge in mice. These responses were further enhanced when combined with a synthetic TLR4 ligand adjuvant. Despite differences between human and mouse TLR7/8, these novel lipidated imidazoquinolines induced the production of cytokines required to polarize a Th1 and Th17 immune response in human PBMCs providing additional support for further development of these compounds as novel adjuvants for the induction of broad supra-seasonal protection from influenza virus.
    MeSH term(s) Adjuvants, Immunologic ; Animals ; Cross Reactions ; Disease Models, Animal ; Female ; HEK293 Cells ; Humans ; Imidazoles/chemical synthesis ; Imidazoles/immunology ; Immunity, Heterologous ; Immunity, Humoral ; Influenza A Virus, H1N1 Subtype/physiology ; Influenza A Virus, H3N2 Subtype/physiology ; Influenza B virus/physiology ; Influenza Vaccines/immunology ; Influenza, Human/immunology ; Lipids/chemical synthesis ; Lymphocyte Activation ; Mice ; Mice, Inbred BALB C ; Orthomyxoviridae Infections/immunology ; Quinolines/chemical synthesis ; Quinolines/immunology ; Th1 Cells/immunology ; Th17 Cells/immunology ; Toll-Like Receptor 7/agonists ; Toll-Like Receptor 8/agonists
    Chemical Substances Adjuvants, Immunologic ; Imidazoles ; Influenza Vaccines ; Lipids ; Quinolines ; TLR7 protein, human ; TLR8 protein, human ; Toll-Like Receptor 7 ; Toll-Like Receptor 8 ; imidazo(4,5-g)quinoline
    Language English
    Publishing date 2020-03-10
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2020.00406
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Identification and Characterization of Stimulator of Interferon Genes As a Robust Adjuvant Target for Early Life Immunization.

    Borriello, Francesco / Pietrasanta, Carlo / Lai, Jacqueline C Y / Walsh, Lois M / Sharma, Pankaj / O'Driscoll, David N / Ramirez, Juan / Brightman, Spencer / Pugni, Lorenza / Mosca, Fabio / Burkhart, David J / Dowling, David J / Levy, Ofer

    Frontiers in immunology

    2017  Volume 8, Page(s) 1772

    Abstract: Immunization is key to preventing infectious diseases, a leading cause of death early in life. However, due to age-specific immunity, vaccines often demonstrate reduced efficacy in newborns and young infants as compared to adults. Here, we ... ...

    Abstract Immunization is key to preventing infectious diseases, a leading cause of death early in life. However, due to age-specific immunity, vaccines often demonstrate reduced efficacy in newborns and young infants as compared to adults. Here, we combined
    Language English
    Publishing date 2017
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2606827-8
    ISSN 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2017.01772
    Database MEDical Literature Analysis and Retrieval System OnLINE

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