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
2022-05-17Author
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
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Copyright 2022
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Show full item recordAbstract
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.
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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.
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