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

  • J Am Chem Soc. 2023 Jul 26;145(29):15838-15847. doi: 10.1021/jacs.3c02679.
Keita Ito  1 Hiroto Furukawa  2 Hiroshi Inaba  2  3 Shino Ohshima  4 Yoshie Kametani  4 Masatoshi Maeki  5 Manabu Tokeshi  5 Xuhao Huang  1 Kazuya Kabayama  1  6 Yoshiyuki Manabe  1  6 Koichi Fukase  1  6  7 Kazunori Matsuura  2  3
Affiliations
  • 1. Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka 560-0043, Osaka, Japan.
  • 2. Department of Chemistry and Biotechnology, Graduate School of Engineering, Tottori University, 4-101 Koyama-Minami, Tottori 680-8552, Japan.
  • 3. Center for Research on Green Sustainable Chemistry, Tottori University, 4-101 Koyama-Minami, Tottori 680-8552, Japan.
  • 4. School of Medicine, Tokai University, Isehara 259-1193, Kanagawa, Japan.
  • 5. Division of Applied Chemistry, Faculty of Engineering, Hokkaido University, Sapporo 060-8628, Hokkaido, Japan.
  • 6. Forefront Research Center, Osaka University, 1-1 Machikaneyama, Toyonaka 560-0043, Osaka, Japan.
  • 7. Center for Advanced Modalities and DDS, Osaka University, 1-1 Yamadaoka, Suita 565-0871, Osaka, Japan.
Abstract

We report a promising Cancer vaccine candidate comprising antigen/adjuvant-displaying enveloped viral replica as a novel vaccine platform. The artificial viral capsid, which consists of a self-assembled β-annulus peptide conjugated with an HER2-derived antigenic CH401 peptide, was enveloped within a lipid bilayer containing the lipidic Adjuvant α-GalCer. The use of an artificial viral capsid as a scaffold enabled precise control of its size to ∼100 nm, which is generally considered to be optimal for delivery to lymph nodes. The encapsulation of the anionically charged capsid by a cationic lipid bilayer dramatically improved its stability and converted its surface charge to cationic, enhancing its uptake by dendritic cells. The developed CH401/α-GalCer-displaying enveloped viral replica exhibited remarkable antibody-production activity. This study represents a pioneering example of precise vaccine design through bottom-up construction and opens new avenues for the development of effective vaccines.

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