Antigen-adjuvant interactions, stability, and immunogenicity profiles of a SARS-CoV-2 receptor-binding domain (RBD) antigen formulated with aluminum salt and CpG adjuvants
Name
Antigen-adjuvant interactions stability and immunogenicity profiles of a SARS-CoV-2 receptor-binding domain RBD antigen formulated with aluminum s.pdf
Description
Published version
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9.62 MB
Format
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Checksum (MD5)
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Author(s)
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
Date Issued
June 6, 2022
Journal
Human Vaccines & Immunotherapeutics
Publisher
Informa UK Limited
Citation
Bajoria, S., Kaur, K., Kumru, O. S., Van Slyke, G., Doering, J., Novak, H., … Volkin, D. B. (2022). Antigen-adjuvant interactions, stability, and immunogenicity profiles of a SARS-CoV-2 receptor-binding domain (RBD) antigen formulated with aluminum salt and CpG adjuvants. Human Vaccines & Immunotherapeutics, 18(5).
Version
Final published version
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 receptorbinding domain (RBD) of SARS-CoV-2 Spike protein 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 antigenadjuvant interactions on the stability and mouse immunogenicity 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 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, the 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.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Koch Institute for Integrative Cancer Research at MIT
Massachusetts Institute of Technology. Department of Chemical Engineering
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DOI of Published Version
https://doi.org/10.1080/21645515.2022.2079346
