A design strategy to generate a SARS-CoV-2 RBD vaccine that abrogates ACE2 binding and improves neutralizing antibody responses.
BIBAX
Body-inert B-cell-activating vaccines
Receptor-binding abrogation
SARS-CoV-2 vaccine
Vaccine design
Journal
European journal of immunology
ISSN: 1521-4141
Titre abrégé: Eur J Immunol
Pays: Germany
ID NLM: 1273201
Informations de publication
Date de publication:
10 2023
10 2023
Historique:
revised:
27
06
2023
received:
27
01
2023
accepted:
27
06
2023
medline:
23
10
2023
pubmed:
12
7
2023
entrez:
12
7
2023
Statut:
ppublish
Résumé
The structure-based design of antigens holds promise for developing vaccines with higher efficacy and improved safety profiles. We postulate that abrogation of host receptor interaction bears potential for the improvement of vaccines by preventing antigen-induced modification of receptor function as well as the displacement or masking of the immunogen. Antigen modifications may yet destroy epitopes crucial for antibody neutralization. Here, we present a methodology that integrates deep mutational scans to identify and score SARS-CoV-2 receptor binding domain variants that maintain immunogenicity, but lack interaction with the widely expressed host receptor. Single point mutations were scored in silico, validated in vitro, and applied in vivo. Our top-scoring variant receptor binding domain-G502E prevented spike-induced cell-to-cell fusion, receptor internalization, and improved neutralizing antibody responses by 3.3-fold in rabbit immunizations. We name our strategy BIBAX for body-inert, B-cell-activating vaccines, which in the future may be applied beyond SARS-CoV-2 for the improvement of vaccines by design.
Identifiants
pubmed: 37435628
doi: 10.1002/eji.202350408
doi:
Substances chimiques
COVID-19 Vaccines
0
Antibodies, Neutralizing
0
Angiotensin-Converting Enzyme 2
EC 3.4.17.23
Antibodies, Viral
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2350408Informations de copyright
© 2023 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.
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