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    Antigen-adjuvant interactions, stability, and immunogenicity profiles of a SARS-CoV-2 receptor-binding domain (RBD) antigen formulated with aluminum salt and CpG adjuvants (Datasets)

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    Issue Date
    2022-05-17
    Author
    Bajoria, Sakshi
    Kaur, Kawaljit
    Kumru, Ozan S.
    Van Slyke, Greta
    Doering, Jennifer
    Novak, Hayley
    Rodriguez-Aponte, Sergio A.
    Dalvie, Neil C.
    Naranjo, Christopher A.
    Johnston, Ryan S.
    Maxwell Silverman, Judith
    Kleanthous, Harry
    Love, J. Christopher
    Mantis, Nicholas J.
    Joshi, Sangeeta B.
    Volkin, David B.
    Type
    Dataset
    Rights
    Copyright 2022
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    Abstract
    Low-cost, refrigerator-stable COVID-19 vaccines will facilitate global access and improve vaccine coverage in low-and middle-income countries. To this end, subunit-based approaches targeting the receptor-binding domain (RBD) remain attractive. Antibodies against RBD neutralize SARS-CoV-2 by blocking viral attachment to the host cell receptor, ACE2. Here, a yeast-produced recombinant RBD antigen (RBD-L452K-F490W or RBD-J) was formulated with various combinations of aluminum-salt (Alhydrogel®, AH; AdjuPhos®, AP) and CpG 1018 adjuvants. We assessed the effect of antigen-adjuvant interactions on stability and mouse immunogenicity profiles of various RBD-J preparations. While RBD-J was ~50% adsorbed to AH and <15% to AP, addition of CpG resulted in complete AH binding, yet no improvement in AP adsorption. ACE2 competition ELISA analyses of formulated RBD-J stored at varying temperatures (4, 25, 37˚C) revealed that RBD-J was destabilized by AH, an effect exacerbated by CpG. DSC studies demonstrated that aluminum salt and CpG adjuvants decrease the conformational stability of RBD-J and suggest a direct CpG-RBD-J interaction. Although AH+CpG-adjuvanted RBD-J was the least stable in vitro, the formulation was the most potent at eliciting SARS-CoV-2 pseudovirus neutralizing antibodies in mice. In contrast, RBD-J formulated with AP+CpG showed minimal antigen-adjuvant interactions, a better stability profile, but suboptimal immune responses. Interestingly, loss of in vivo potency associated with heat-stressed RBD-J formulated with AH+CpG after one dose was abrogated by a booster. Our findings highlight the importance of elucidating the key interrelationships between antigen-adjuvant interactions, storage stability, and in vivo performance to enable successful formulation development of stable and efficacious subunit vaccines.
    Description
    This record contains datasets from the article, Antigen-adjuvant interactions, stability, and immunogenicity profiles of a SARS-CoV-2 receptor-binding domain (RBD) antigen formulated with aluminum salt and CpG adjuvants, https://doi.org/10.1080/21645515.2022.2079346, published in the journal Human Vaccines and Immunotherapeutics.
    URI
    http://hdl.handle.net/1808/32758
    DOI
    https://doi.org/10.17161/1808.32758
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    • Pharmaceutical Chemistry Scholarly Works [343]

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    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

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