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  1. Article ; Online: Engineered immunogens to elicit antibodies against conserved coronavirus epitopes

    A. Brenda Kapingidza / Daniel J. Marston / Caitlin Harris / Daniel Wrapp / Kaitlyn Winters / Dieter Mielke / Lu Xiaozhi / Qi Yin / Andrew Foulger / Rob Parks / Maggie Barr / Amanda Newman / Alexandra Schäfer / Amanda Eaton / Justine Mae Flores / Austin Harner / Nicholas J. Catanzaro / Michael L. Mallory / Melissa D. Mattocks /
    Christopher Beverly / Brianna Rhodes / Katayoun Mansouri / Elizabeth Van Itallie / Pranay Vure / Brooke Dunn / Taylor Keyes / Sherry Stanfield-Oakley / Christopher W. Woods / Elizabeth A. Petzold / Emmanuel B. Walter / Kevin Wiehe / Robert J. Edwards / David C. Montefiori / Guido Ferrari / Ralph Baric / Derek W. Cain / Kevin O. Saunders / Barton F. Haynes / Mihai L. Azoitei

    Nature Communications, Vol 14, Iss 1, Pp 1-

    2023  Volume 18

    Abstract: Abstract Immune responses to SARS-CoV-2 primarily target the receptor binding domain of the spike protein, which continually mutates to escape acquired immunity. Other regions in the spike S2 subunit, such as the stem helix and the segment encompassing ... ...

    Abstract Abstract Immune responses to SARS-CoV-2 primarily target the receptor binding domain of the spike protein, which continually mutates to escape acquired immunity. Other regions in the spike S2 subunit, such as the stem helix and the segment encompassing residues 815-823 adjacent to the fusion peptide, are highly conserved across sarbecoviruses and are recognized by broadly reactive antibodies, providing hope that vaccines targeting these epitopes could offer protection against both current and emergent viruses. Here we employ computational modeling to design scaffolded immunogens that display the spike 815-823 peptide and the stem helix epitopes without the distracting and immunodominant receptor binding domain. These engineered proteins bind with high affinity and specificity to the mature and germline versions of previously identified broadly protective human antibodies. Epitope scaffolds interact with both sera and isolated monoclonal antibodies with broadly reactivity from individuals with pre-existing SARS-CoV-2 immunity. When used as immunogens, epitope scaffolds elicit sera with broad betacoronavirus reactivity and protect as “boosts” against live virus challenge in mice, illustrating their potential as components of a future pancoronavirus vaccine.
    Keywords Science ; Q
    Subject code 570
    Language English
    Publishing date 2023-11-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: The Chimpanzee SIV Envelope Trimer

    Raiees Andrabi / Jesper Pallesen / Joel D. Allen / Ge Song / Jinsong Zhang / Natalia de Val / Gavin Gegg / Katelyn Porter / Ching-Yao Su / Matthias Pauthner / Amanda Newman / Hilary Bouton-Verville / Fernando Garces / Ian A. Wilson / Max Crispin / Beatrice H. Hahn / Barton F. Haynes / Laurent Verkoczy / Andrew B. Ward /
    Dennis R. Burton

    Cell Reports, Vol 27, Iss 8, Pp 2426-2441.e

    Structure and Deployment as an HIV Vaccine Template

    2019  Volume 6

    Abstract: Summary: Epitope-targeted HIV vaccine design seeks to focus antibody responses to broadly neutralizing antibody (bnAb) sites by sequential immunization. A chimpanzee simian immunodeficiency virus (SIV) envelope (Env) shares a single bnAb site, the ... ...

    Abstract Summary: Epitope-targeted HIV vaccine design seeks to focus antibody responses to broadly neutralizing antibody (bnAb) sites by sequential immunization. A chimpanzee simian immunodeficiency virus (SIV) envelope (Env) shares a single bnAb site, the variable loop 2 (V2)-apex, with HIV, suggesting its possible utility in an HIV immunization strategy. Here, we generate a chimpanzee SIV Env trimer, MT145K, which displays selective binding to HIV V2-apex bnAbs and precursor versions, but no binding to other HIV specificities. We determine the structure of the MT145K trimer by cryo-EM and show that its architecture is remarkably similar to HIV Env. Immunization of an HIV V2-apex bnAb precursor Ab-expressing knockin mouse with the chimpanzee MT145K trimer induces HIV V2-specific neutralizing responses. Subsequent boosting with an HIV trimer cocktail induces responses that exhibit some virus cross-neutralization. Overall, the chimpanzee MT145K trimer behaves as expected from design both in vitro and in vivo and is an attractive potential component of a sequential immunization regimen to induce V2-apex bnAbs. : Design of immunogens and strategies that can induce protective broadly neutralizing antibodies (bnAbs) is a priority for HIV vaccine development. Andrabi et al. design a chimpanzee simian immunodeficiency virus (SIV) envelope trimer immunogen that binds specifically to HIV V2-apex bnAbs and their unmutated versions. The SIV trimer immunogen induces HIV-specific neutralizing antibodies (nAbs) in a favorable animal model. Keywords: human immunodeficiency virus, simian immunodeficiency virus, broadly neutralizing antibodies, HIV envelope trimer, chimpanzee SIV envelope trimer, glycan shield, V2-apex bnAb site, immunization strategies, HIV vaccine
    Keywords Biology (General) ; QH301-705.5
    Language English
    Publishing date 2019-05-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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  3. Article ; Online: Vaccine Induction of Heterologous Tier 2 HIV-1 Neutralizing Antibodies in Animal Models

    Kevin O. Saunders / Laurent K. Verkoczy / Chuancang Jiang / Jinsong Zhang / Robert Parks / Haiyan Chen / Max Housman / Hilary Bouton-Verville / Xiaoying Shen / Ashley M. Trama / Richard Scearce / Laura Sutherland / Sampa Santra / Amanda Newman / Amanda Eaton / Kai Xu / Ivelin S. Georgiev / M. Gordon Joyce / Georgia D. Tomaras /
    Mattia Bonsignori / Steven G. Reed / Andres Salazar / John R. Mascola / M. Anthony Moody / Derek W. Cain / Mireille Centlivre / Sandra Zurawski / Gerard Zurawski / Harold P. Erickson / Peter D. Kwong / S. Munir Alam / Yves Levy / David C. Montefiori / Barton F. Haynes

    Cell Reports, Vol 21, Iss 13, Pp 3681-

    2017  Volume 3690

    Abstract: The events required for the induction of broad neutralizing antibodies (bnAbs) following HIV-1 envelope (Env) vaccination are unknown, and their induction in animal models as proof of concept would be critical. Here, we describe the induction of plasma ... ...

    Abstract The events required for the induction of broad neutralizing antibodies (bnAbs) following HIV-1 envelope (Env) vaccination are unknown, and their induction in animal models as proof of concept would be critical. Here, we describe the induction of plasma antibodies capable of neutralizing heterologous primary (tier 2) HIV-1 strains in one macaque and two rabbits. Env immunogens were designed to induce CD4 binding site (CD4bs) bnAbs, but surprisingly, the macaque developed V1V2-glycan bnAbs. Env immunization of CD4bs bnAb heavy chain rearrangement (VHDJH) knockin mice similarly induced V1V2-glycan neutralizing antibodies (nAbs), wherein the human CD4bs VH chains were replaced with mouse rearrangements bearing diversity region (D)-D fusions, creating antibodies with long, tyrosine-rich HCDR3s. Our results show that Env vaccination can elicit broad neutralization of tier 2 HIV-1, demonstrate that V1V2-glycan bnAbs are more readily induced than CD4bs bnAbs, and define VH replacement and diversity region fusion as potential mechanisms for generating V1V2-glycan bnAb site antibodies.
    Keywords HIV vaccine ; broadly neutralizing antibodies ; knockin mice ; CH103 ; CH505 ; Biology (General) ; QH301-705.5
    Subject code 570
    Language English
    Publishing date 2017-12-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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  4. Article ; Online: Initiation of HIV neutralizing B cell lineages with sequential envelope immunizations

    Wilton B. Williams / Jinsong Zhang / Chuancang Jiang / Nathan I. Nicely / Daniela Fera / Kan Luo / M. Anthony Moody / Hua-Xin Liao / S. Munir Alam / Thomas B. Kepler / Akshaya Ramesh / Kevin Wiehe / James A. Holland / Todd Bradley / Nathan Vandergrift / Kevin O. Saunders / Robert Parks / Andrew Foulger / Shi-Mao Xia /
    Mattia Bonsignori / David C. Montefiori / Mark Louder / Amanda Eaton / Sampa Santra / Richard Scearce / Laura Sutherland / Amanda Newman / Hilary Bouton-Verville / Cindy Bowman / Howard Bomze / Feng Gao / Dawn J. Marshall / John F. Whitesides / Xiaoyan Nie / Garnett Kelsoe / Steven G. Reed / Christopher B. Fox / Kim Clary / Marguerite Koutsoukos / David Franco / John R. Mascola / Stephen C. Harrison / Barton F. Haynes / Laurent Verkoczy

    Nature Communications, Vol 8, Iss 1, Pp 1-

    2017  Volume 20

    Abstract: An efficient HIV-1 vaccine will likely depend on eliciting broadly neutralizing antibodies (bnAb). Here the authors analyze the B cell repertoire in macaques and knock-in mice in response to sequential immunization with Env variants that induce a bnAb ... ...

    Abstract An efficient HIV-1 vaccine will likely depend on eliciting broadly neutralizing antibodies (bnAb). Here the authors analyze the B cell repertoire in macaques and knock-in mice in response to sequential immunization with Env variants that induce a bnAb targeting the CD4-binding site of Env in a HIV-1 infected individual.
    Keywords Science ; Q
    Language English
    Publishing date 2017-11-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

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