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  1. Artikel ; Online: Bringing immunofocusing into focus.

    Musunuri, Sriharshita / Weidenbacher, Payton A B / Kim, Peter S

    NPJ vaccines

    2024  Band 9, Heft 1, Seite(n) 11

    Abstract: Immunofocusing is a strategy to create immunogens that redirect humoral immune responses towards a targeted epitope and away from non-desirable epitopes. Immunofocusing methods often aim to develop "universal" vaccines that provide broad protection ... ...

    Abstract Immunofocusing is a strategy to create immunogens that redirect humoral immune responses towards a targeted epitope and away from non-desirable epitopes. Immunofocusing methods often aim to develop "universal" vaccines that provide broad protection against highly variant viruses such as influenza virus, human immunodeficiency virus (HIV-1), and most recently, severe acute respiratory syndrome coronavirus (SARS-CoV-2). We use existing examples to illustrate five main immunofocusing strategies-cross-strain boosting, mosaic display, protein dissection, epitope scaffolding, and epitope masking. We also discuss obstacles for immunofocusing like immune imprinting. A thorough understanding, advancement, and application of the methods we outline here will enable the design of high-resolution vaccines that protect against future viral outbreaks.
    Sprache Englisch
    Erscheinungsdatum 2024-01-09
    Erscheinungsland England
    Dokumenttyp Journal Article ; Review
    ISSN 2059-0105
    ISSN (online) 2059-0105
    DOI 10.1038/s41541-023-00792-x
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: Rapid Proliferation of Pandemic Research: Implications for Dual-Use Risks.

    Musunuri, Sriharshita / Sandbrink, Jonas B / Monrad, Joshua Teperowski / Palmer, Megan J / Koblentz, Gregory D

    mBio

    2021  Band 12, Heft 5, Seite(n) e0186421

    Abstract: The COVID-19 pandemic has demonstrated the world's vulnerability to biological catastrophe and elicited unprecedented scientific efforts. Some of this work and its derivatives, however, present dual-use risks (i.e., potential harm from misapplication of ... ...

    Abstract The COVID-19 pandemic has demonstrated the world's vulnerability to biological catastrophe and elicited unprecedented scientific efforts. Some of this work and its derivatives, however, present dual-use risks (i.e., potential harm from misapplication of beneficial research) that have largely gone unaddressed. For instance, gain-of-function studies and reverse genetics protocols may facilitate the engineering of concerning SARS-CoV-2 variants and other pathogens. The risk of accidental or deliberate release of dangerous pathogens may be increased by large-scale collection and characterization of zoonotic viruses undertaken in an effort to understand what enables animal-to-human transmission. These concerns are exacerbated by the rise of preprint publishing that circumvents a late-stage opportunity for dual-use oversight. To prevent the next global health emergency, we must avoid inadvertently increasing the threat of future biological events. This requires a nuanced and proactive approach to dual-use evaluation throughout the research life cycle, including the conception, funding, conduct, and dissemination of research.
    Mesh-Begriff(e) COVID-19/epidemiology ; Containment of Biohazards ; Global Health/statistics & numerical data ; Humans ; Pandemics
    Sprache Englisch
    Erscheinungsdatum 2021-10-19
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2557172-2
    ISSN 2150-7511 ; 2161-2129
    ISSN (online) 2150-7511
    ISSN 2161-2129
    DOI 10.1128/mBio.01864-21
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel ; Online: Simplified Purification of Glycoprotein-Modified Ferritin Nanoparticles for Vaccine Development.

    Weidenbacher, Payton / Musunuri, Sriharshita / Powell, Abigail E / Tang, Shaogeng / Do, Jonathan / Sanyal, Mrinmoy / Kim, Peter S

    Biochemistry

    2022  Band 62, Heft 2, Seite(n) 292–299

    Abstract: Ferritin-based, self-assembling protein nanoparticle vaccines are being developed against a range of viral pathogens, including SARS-CoV-2, influenza, HIV-1, and Epstein-Barr virus. However, purification of these nanoparticles is often laborious and ... ...

    Abstract Ferritin-based, self-assembling protein nanoparticle vaccines are being developed against a range of viral pathogens, including SARS-CoV-2, influenza, HIV-1, and Epstein-Barr virus. However, purification of these nanoparticles is often laborious and requires customization for each potential nanoparticle vaccine. We propose that the simple insertion of a polyhistidine tag into exposed flexible loops on the ferritin surface (His-Fer) can mitigate the need for complex purifications and enable facile metal-chelate-based purification, thereby allowing for optimization of early stage vaccine candidates. Using sequence homology and computational modeling, we identify four sites that can accommodate insertion of a polyhistidine tag and demonstrate purification of both hemagglutinin-modified and SARS-CoV-2 spike-modified ferritins, highlighting the generality of the approach. A site at the 4-fold axis of symmetry enables optimal purification of both protein nanoparticles. We demonstrate improved purification through modulating the polyhistidine length and optimizing both the metal cation and the resin type. Finally, we show that purified His-Fer proteins remain multimeric and elicit robust immune responses similar to those of their wild-type counterparts. Collectively, this work provides a simplified purification scheme for ferritin-based vaccines.
    Mesh-Begriff(e) Humans ; Antibodies, Neutralizing ; COVID-19/prevention & control ; Ferritins/chemistry ; Glycoproteins/chemistry ; Nanoparticles ; SARS-CoV-2 ; Spike Glycoprotein, Coronavirus/chemistry ; Vaccine Development
    Chemische Substanzen Antibodies, Neutralizing ; Ferritins (9007-73-2) ; Glycoproteins ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
    Sprache Englisch
    Erscheinungsdatum 2022-08-12
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1108-3
    ISSN 1520-4995 ; 0006-2960
    ISSN (online) 1520-4995
    ISSN 0006-2960
    DOI 10.1021/acs.biochem.2c00241
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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