dc.contributor.author | Bajoria, Sakshi | |
dc.contributor.author | Kaur, Kawaljit | |
dc.contributor.author | Kumru, Ozan S. | |
dc.contributor.author | Van Slyke, Greta | |
dc.contributor.author | Doering, Jennifer | |
dc.contributor.author | Novak, Hayley | |
dc.contributor.author | Rodriguez-Aponte, Sergio A. | |
dc.contributor.author | Dalvie, Neil C. | |
dc.contributor.author | Naranjo, Christopher A. | |
dc.contributor.author | Johnston, Ryan S. | |
dc.contributor.author | Maxwell Silverman, Judith | |
dc.contributor.author | Kleanthous, Harry | |
dc.contributor.author | Love, J. Christopher | |
dc.contributor.author | Mantis, Nicholas J. | |
dc.contributor.author | Joshi, Sangeeta B. | |
dc.contributor.author | Volkin, David B. | |
dc.date.accessioned | 2022-05-10T22:35:00Z | |
dc.date.available | 2022-05-10T22:35:00Z | |
dc.date.issued | 2022-05-17 | |
dc.identifier.uri | http://hdl.handle.net/1808/32758 | |
dc.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. | en_US |
dc.description.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. | en_US |
dc.rights | Copyright 2022 | en_US |
dc.subject | COVID-19 | en_US |
dc.subject | Vaccine | en_US |
dc.subject | RBD | en_US |
dc.subject | Adjuvant | en_US |
dc.subject | Formulation | en_US |
dc.subject | Stability | en_US |
dc.subject | Immunogenicity | en_US |
dc.title | 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) | en_US |
dc.type | Dataset | en_US |
kusw.kuauthor | Hickey, John | |
kusw.kudepartment | Pharmaceutical Chemistry | en_US |
dc.identifier.doi | 10.17161/1808.32758 | |
dc.rights.accessrights | openAccess | en_US |