Novel sialoglycan linkage for constructing adjuvant-protein conjugate as potent vaccine for COVID-19.
J Control Release
; 355: 238-247, 2023 03.
Article
in English
| MEDLINE | ID: covidwho-2236929
ABSTRACT
Self-adjuvanting protein vaccines have been proved to be highly immunogenic with efficient codelivery of adjuvant and antigen. Current protein vaccines with built-in adjuvants are all modified at the peptide backbone of antigen protein, which could not achieve minor epitope interference and adjuvant multivalency at the same time. Herein, we developed a new conjugate strategy to construct effective adjuvant-protein vaccine with adjuvant cluster effect and minimal epitope interference. The toll-like receptor 7 agonist (TLR7a) is covalently conjugated on the terminal sialoglycans of SARS-CoV-2-S1 protein, leading to intracellular release of the small-molecule stimulators with greatly reduced risks of systemic toxicity. The resulting TLR7a-S1 conjugate elicited strong activation of immune cells in vitro, and potent antibody and cellular responses with a significantly enhanced Th1-bias in vivo. TLR7a-S1-induced antibody also effectively cross-neutralized all variants of concern. This sialoglycoconjugation approach to construct protein conjugate vaccines will have more applications to combat SARS-CoV-2 and other diseases.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
COVID-19 Vaccines
/
COVID-19
Type of study:
Prognostic study
/
Randomized controlled trials
Topics:
Vaccines
/
Variants
Limits:
Humans
Language:
English
Journal:
J Control Release
Journal subject:
Pharmacology
Year:
2023
Document Type:
Article
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