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  1. Article ; Online: Vaccine design via antigen reorientation.

    Xu, Duo / Carter, Joshua J / Li, Chunfeng / Utz, Ashley / Weidenbacher, Payton A B / Tang, Shaogeng / Sanyal, Mrinmoy / Pulendran, Bali / Barnes, Christopher O / Kim, Peter S

    Nature chemical biology

    2024  

    Abstract: A major challenge in creating universal influenza vaccines is to focus immune responses away from the immunodominant, variable head region of hemagglutinin (HA-head) and toward the evolutionarily conserved stem region (HA-stem). Here we introduce an ... ...

    Abstract A major challenge in creating universal influenza vaccines is to focus immune responses away from the immunodominant, variable head region of hemagglutinin (HA-head) and toward the evolutionarily conserved stem region (HA-stem). Here we introduce an approach to control antigen orientation via site-specific insertion of aspartate residues that facilitates antigen binding to alum. We demonstrate the generalizability of this approach with antigens from Ebola, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza viruses and observe enhanced neutralizing antibody responses in all cases. We then reorient an H2 HA in an 'upside-down' configuration to increase the exposure and immunogenicity of HA-stem. The reoriented H2 HA (reoH2HA) on alum induced stem-directed antibodies that cross-react with both group 1 and group 2 influenza A subtypes. Electron microscopy polyclonal epitope mapping (EMPEM) revealed that reoH2HA (group 1) elicits cross-reactive antibodies targeting group 2 HA-stems. Our results highlight antigen reorientation as a generalizable approach for designing epitope-focused vaccines.
    Language English
    Publishing date 2024-01-15
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2202962-X
    ISSN 1552-4469 ; 1552-4450
    ISSN (online) 1552-4469
    ISSN 1552-4450
    DOI 10.1038/s41589-023-01529-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Design of universal Ebola virus vaccine candidates via immunofocusing.

    Xu, Duo / Powell, Abigail E / Utz, Ashley / Sanyal, Mrinmoy / Do, Jonathan / Patten, J J / Moliva, Juan I / Sullivan, Nancy J / Davey, Robert A / Kim, Peter S

    Proceedings of the National Academy of Sciences of the United States of America

    2024  Volume 121, Issue 7, Page(s) e2316960121

    Abstract: The Ebola virus causes hemorrhagic fever in humans and poses a significant threat to global public health. Although two viral vector vaccines have been approved to prevent Ebola virus disease, they are distributed in the limited ring vaccination setting ... ...

    Abstract The Ebola virus causes hemorrhagic fever in humans and poses a significant threat to global public health. Although two viral vector vaccines have been approved to prevent Ebola virus disease, they are distributed in the limited ring vaccination setting and only indicated for prevention of infection from
    MeSH term(s) Humans ; Animals ; Mice ; Hemorrhagic Fever, Ebola ; Ebola Vaccines ; Antibodies, Viral ; Ebolavirus ; Antibodies, Neutralizing ; Viral Vaccines ; Immune Sera
    Chemical Substances Ebola Vaccines ; Antibodies, Viral ; Antibodies, Neutralizing ; Viral Vaccines ; Immune Sera
    Language English
    Publishing date 2024-02-06
    Publishing country United States
    Document type Journal Article
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.2316960121
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Computation-Guided Rational Design of a Peptide Motif That Reacts with Cyanobenzothiazoles via Internal Cysteine-Lysine Relay.

    Keyser, Samantha G L / Utz, Ashley / Bertozzi, Carolyn R

    The Journal of organic chemistry

    2018  Volume 83, Issue 14, Page(s) 7467–7479

    Abstract: Site-selective protein modification based on covalent reactions of peptide tags and small molecules is a key capability for basic research as well as for the development of new therapeutic bioconjugates. Here, we describe the computation-guided rational ... ...

    Abstract Site-selective protein modification based on covalent reactions of peptide tags and small molecules is a key capability for basic research as well as for the development of new therapeutic bioconjugates. Here, we describe the computation-guided rational design of a cysteine- and lysine-containing 11-residue peptide sequence that reacts with 2-cyanobenzothiazole (CBT) derivatives. Our data show that the cysteine residue reversibly reacts with the nitrile group on the CBT moiety to form an intermediate thioimidate, which undergoes irreversible SN transfer to the lysine residue, yielding an amidine-linked product. The concepts outlined herein lay a foundation for future development of peptide tags in the context of site-selective modification of lysine residues within engineered microenvironments.
    MeSH term(s) Amino Acid Sequence ; Cell Surface Display Techniques ; Computer Simulation ; Cysteine/chemistry ; Lysine/chemistry ; Models, Molecular ; Peptides/chemical synthesis ; Protein Conformation
    Chemical Substances Peptides ; Lysine (K3Z4F929H6) ; Cysteine (K848JZ4886)
    Language English
    Publishing date 2018-05-30
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 123490-0
    ISSN 1520-6904 ; 0022-3263
    ISSN (online) 1520-6904
    ISSN 0022-3263
    DOI 10.1021/acs.joc.8b00625
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 4473: Show issues Location:
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  4. Article: Designing epitope-focused vaccines

    Xu, Duo / Li, Chunfeng / Utz, Ashley / Weidenbacher, Payton A B / Tang, Shaogeng / Sanyal, Mrinmoy / Pulendran, Bali / Kim, Peter S

    bioRxiv : the preprint server for biology

    2022  

    Abstract: A major challenge in vaccine development, especially against rapidly evolving viruses, is the ability to focus the immune response toward evolutionarily conserved antigenic regions to confer broad protection. For example, while many broadly neutralizing ... ...

    Abstract A major challenge in vaccine development, especially against rapidly evolving viruses, is the ability to focus the immune response toward evolutionarily conserved antigenic regions to confer broad protection. For example, while many broadly neutralizing antibodies against influenza have been found to target the highly conserved stem region of hemagglutinin (HA-stem), the immune response to seasonal influenza vaccines is predominantly directed to the immunodominant but variable head region (HA-head), leading to narrow-spectrum efficacy. Here, we first introduce an approach to controlling antigen orientation based on the site-specific insertion of short stretches of aspartate residues (oligoD) that facilitates antigen-binding to alum adjuvants. We demonstrate the generalizability of this approach to antigens from the Ebola virus, SARS-CoV-2, and influenza and observe enhanced antibody responses following immunization in all cases. Next, we use this approach to reorient HA in an "upside down" configuration, which we envision increases HA-stem exposure, therefore also improving its immunogenicity compared to HA-head. When applied to HA of H2N2 A/Japan/305/1957, the reoriented H2 HA (reoH2HA) on alum induced a stem-directed antibody response that cross-reacted with both group 1 and 2 influenza A HAs. Our results demonstrate the possibility and benefits of antigen reorientation
    Language English
    Publishing date 2022-12-21
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2022.12.20.521291
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Design of universal Ebola virus vaccine candidates

    Xu, Duo / Powell, Abigail E / Utz, Ashley / Sanyal, Mrinmoy / Do, Jonathan / Patten, J J / Moliva, Juan I / Sullivan, Nancy J / Davey, Robert A / Kim, Peter S

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Ebola virus causes hemorrhagic fever in humans and poses a significant threat to global public health. Although two viral vector vaccines have been approved to prevent Ebola virus disease, they are distributed in the limited ring vaccination setting and ... ...

    Abstract Ebola virus causes hemorrhagic fever in humans and poses a significant threat to global public health. Although two viral vector vaccines have been approved to prevent Ebola virus disease, they are distributed in the limited ring vaccination setting and only indicated for prevention of infection from
    Language English
    Publishing date 2023-10-17
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.10.14.562364
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Computation-Guided Rational Design of a Peptide Motif That Reacts with Cyanobenzothiazoles via Internal Cysteine–Lysine Relay

    Keyser, Samantha G. L / Utz, Ashley / Bertozzi, Carolyn R

    Journal of organic chemistry. 2018 May 17, v. 83, no. 14

    2018  

    Abstract: Site-selective protein modification based on covalent reactions of peptide tags and small molecules is a key capability for basic research as well as for the development of new therapeutic bioconjugates. Here, we describe the computation-guided rational ... ...

    Abstract Site-selective protein modification based on covalent reactions of peptide tags and small molecules is a key capability for basic research as well as for the development of new therapeutic bioconjugates. Here, we describe the computation-guided rational design of a cysteine- and lysine-containing 11-residue peptide sequence that reacts with 2-cyanobenzothiazole (CBT) derivatives. Our data show that the cysteine residue reversibly reacts with the nitrile group on the CBT moiety to form an intermediate thioimidate, which undergoes irreversible SN transfer to the lysine residue, yielding an amidine-linked product. The concepts outlined herein lay a foundation for future development of peptide tags in the context of site-selective modification of lysine residues within engineered microenvironments.
    Keywords chemical reactions ; cysteine ; lysine ; moieties ; organic chemistry ; protein tagging ; therapeutics
    Language English
    Dates of publication 2018-0517
    Size p. 7467-7479.
    Publishing place American Chemical Society
    Document type Article
    ZDB-ID 123490-0
    ISSN 1520-6904 ; 0022-3263
    ISSN (online) 1520-6904
    ISSN 0022-3263
    DOI 10.1021/acs.joc.8b00625
    Database NAL-Catalogue (AGRICOLA)

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  7. Article ; Online: Toward Point-of-Care Detection of

    Kamariza, Mireille / Keyser, Samantha G L / Utz, Ashley / Knapp, Benjamin D / Ealand, Christopher / Ahn, Green / Cambier, C J / Chen, Teresia / Kana, Bavesh / Huang, Kerwyn Casey / Bertozzi, Carolyn R

    JACS Au

    2021  Volume 1, Issue 9, Page(s) 1368–1379

    Abstract: There is an urgent need for point-of-care tuberculosis (TB) diagnostic methods that are fast, inexpensive, and operationally simple. Here, we report on a bright solvatochromic dye trehalose conjugate that specifically ... ...

    Abstract There is an urgent need for point-of-care tuberculosis (TB) diagnostic methods that are fast, inexpensive, and operationally simple. Here, we report on a bright solvatochromic dye trehalose conjugate that specifically detects
    Language English
    Publishing date 2021-07-26
    Publishing country United States
    Document type Journal Article
    ISSN 2691-3704
    ISSN (online) 2691-3704
    DOI 10.1021/jacsau.1c00173
    Database MEDical Literature Analysis and Retrieval System OnLINE

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