A Click-Type Enzymatic Method for Antigen-Adjuvant Conjugation.
Small Methods
; : e2401116, 2024 Aug 23.
Article
en En
| MEDLINE
| ID: mdl-39177201
ABSTRACT
The Toll-like receptor 9 (TLR9) stimulator, CpG oligodeoxynucleotide, has emerged as a potent enhancer of protein subunit vaccines. Incorporating the protein antigen directly with the CpG adjuvant presents a novel strategy to significantly reduce the required dosage of CpG compared to traditional methods that use separate components. In contrast to existing chemical conjugation methods, this study introduces an enzymatic approach for antigen-adjuvant coupling using a recombinant endonuclease DCV fused with SpyTag. This fusion protein catalyzes the covalent linkage between itself and the CpG adjuvant under mild conditions. These conjugates can be further linked with target protein antigens containing the SpyCatcher sequence, yielding stable, covalently-linked antigen-adjuvant complexes. The corresponding complex utilizing the receptor-binding domain (RBD) of SARS-CoV-2 spike protein as the model antigen, elicits high-titer, specific antibody production in mice via both subcutaneous administration and intratracheal inoculation. Notably, the tumor vaccine candidate fabricated by this method has also shown significant inhibition of cancer progression after intratracheal administration. The technique ensures precise, site-specific coupling and preserves the antigen's structural integrity due to the post-purification coupling strategy that simplifies manufacturing and aids in developing inhalable vaccines.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
Small Methods
Año:
2024
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Alemania