4.8 Article

Antigen/Adjuvant-Displaying Enveloped Viral Replica as a Self-Adjuvanting Anti-Breast-Cancer Vaccine Candidate

Journal

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
Volume 145, Issue 29, Pages 15838-15847

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/jacs.3c02679

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We present a potential cancer vaccine candidate using an antigen/adjuvant-displaying enveloped viral replica as a novel vaccine platform. The capsid, made of self-assembled β-annulus peptide conjugated with an HER2-derived antigenic CH401 peptide, was enclosed within a lipid bilayer containing the lipidic adjuvant α-GalCer. Precise control of the capsid size to approximately 100 nm was achieved using an artificial viral capsid as a scaffold, which is optimal for delivery to lymph nodes. The encapsulation of the capsid by the lipid bilayer improved its stability and enhanced its uptake by dendritic cells through conversion of its surface charge to cationic. The developed CH401/α-GalCer-displaying enveloped viral replica showed remarkable antibody-production activity. This study represents a pioneering example of precise vaccine design through bottom-up construction and opens new avenues for effective vaccine development.
We report a promising cancer vaccine candidate comprisingantigen/adjuvant-displayingenveloped viral replica as a novel vaccine platform. The artificialviral capsid, which consists of a self-assembled & beta;-annulus peptideconjugated with an HER2-derived antigenic CH401 peptide, was envelopedwithin a lipid bilayer containing the lipidic adjuvant & alpha;-GalCer.The use of an artificial viral capsid as a scaffold enabled precisecontrol of its size to & SIM;100 nm, which is generally consideredto be optimal for delivery to lymph nodes. The encapsulation of theanionically charged capsid by a cationic lipid bilayer dramaticallyimproved its stability and converted its surface charge to cationic,enhancing its uptake by dendritic cells. The developed CH401/& alpha;-GalCer-displayingenveloped viral replica exhibited remarkable antibody-production activity.This study represents a pioneering example of precise vaccine designthrough bottom-up construction and opens new avenues for the developmentof effective vaccines.

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