Antigen-adjuvant interactions, stability, and immunogenicity profiles of a SARS-CoV-2 receptor-binding domain (RBD) antigen formulated with aluminum salt and CpG adjuvants.
COVID-19
CpG
RBD
adjuvant
alum
formulation
immunogenicity
stability
vaccine
Journal
Human vaccines & immunotherapeutics
ISSN: 2164-554X
Titre abrégé: Hum Vaccin Immunother
Pays: United States
ID NLM: 101572652
Informations de publication
Date de publication:
30 11 2022
30 11 2022
Historique:
pubmed:
7
6
2022
medline:
2
11
2022
entrez:
6
6
2022
Statut:
ppublish
Résumé
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) 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 antigen-adjuvant 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
Identifiants
pubmed: 35666264
doi: 10.1080/21645515.2022.2079346
pmc: PMC9621007
doi:
Substances chimiques
spike protein, SARS-CoV-2
0
COVID-19 Vaccines
0
Aluminum
CPD4NFA903
Angiotensin-Converting Enzyme 2
EC 3.4.17.23
Spike Glycoprotein, Coronavirus
0
Adjuvants, Immunologic
0
Antibodies, Viral
0
Antibodies, Neutralizing
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2079346Subventions
Organisme : NCI NIH HHS
ID : U01 CA260508
Pays : United States
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