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Immunological Evaluation of Co-Assembling a Lipidated Peptide Antigen and Lipophilic Adjuvants: Self-Adjuvanting Anti-Breast-Cancer Vaccine Candidates
Authors:Taku Aiga  Dr. Yoshiyuki Manabe  Keita Ito  Tsung-Che Chang  Dr. Kazuya Kabayama  Shino Ohshima  Prof. Yoshie Kametani  Ayane Miura  Hiroto Furukawa  Dr. Hiroshi Inaba  Prof. Kazunori Matsuura  Prof. Koichi Fukase
Affiliation:1. Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka, 560-0043 Japan;2. Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka, 560-0043 Japan

Core for Medicine and Science Collaborative Research and Education, Project Research Center for Fundamental Sciences, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka, 560-0043 Japan;3. School of Medicine, Tokai University, Isehara, Kanagawa, 259-1193 Japan;4. Department of Chemistry and Biotechnology, Graduate School of Engineering, Center for Research on Green Sustainable Chemistry, Tottori University, 4-101 Koyama-Minami, Tottori, 680-8552 Japan

Abstract:Co-assembling vaccines composed of a lipidated HER2-derived antigenic CH401 peptide and either a lipophilic adjuvant, Pam3CSK4, α-GalCer, or lipid A 506, were evaluated as breast cancer vaccine candidates. This vaccine design was aimed to inherit both antigen multivalency and antigen-specific immunostimulation properties, observed in reported self-adjuvanting vaccine candidates, by using self-assembly and adjuvant-conjugated antigens. Under vaccination concentrations, respective lipophilic adjuvants underwent co-assembly with lipidated CH401, which boosted the anti-CH401 IgG and IgM production. In particular, α-GalCer was responsible for the most significant immune activation. Therefore, the newly developed vaccine design enabled the optimization of adjuvants against the antigenic CH401 peptide in a simple preparatory manner. Overall, the co-assembling vaccine design opens the door for efficient and practical self-adjuvanting vaccine development.
Keywords:adjuvants  antigens  cancer  peptides  self-assembly
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