Immunological Evaluation of Co‐Assembling a Lipidated Peptide Antigen and Lipophilic Adjuvants: Self‐Adjuvanting Anti‐Breast‐Cancer Vaccine Candidates

• Published in: Angewandte Chemie International Edition 2020-09, Vol.59 (40), p.17705-17711
• Main Authors: Aiga, Taku, Manabe, Yoshiyuki, Ito, Keita, Chang, Tsung‐Che, Kabayama, Kazuya, Ohshima, Shino, Kametani, Yoshie, Miura, Ayane, Furukawa, Hiroto, Inaba, Hiroshi, Matsuura, Kazunori, Fukase, Koichi
• Format: Article
• Language: English
• Subjects: Adjuvants; Adjuvants, Immunologic - chemistry; Animals; Antigens; Antigens - chemistry; Antigens - immunology; Assembling; Assembly; Autoantigens; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; cancer; Cancer vaccines; Cancer Vaccines - chemistry; Cancer Vaccines - therapeutic use; Design; Design optimization; ErbB-2 protein; Female; Galactosylceramides - chemistry; Humans; Immune response; Immunoglobulin G; Immunoglobulin G - blood; Immunoglobulin M; Immunoglobulin M - blood; Immunoglobulin M - immunology; Immunoglobulin M - metabolism; Immunology; Immunostimulation; Immunotherapy; Lipid A; Lipids; Lipopeptides - chemistry; Lipophilic; Lipophilicity; Mice; Mice, Inbred BALB C; Peptides; Peptides - chemistry; Peptides - immunology; self-assembly; Vaccine development; Vaccines
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202007999

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. A co‐assembled vaccine, composed of lipidated antigens and lipophilic adjuvants, is reported. This vaccine design possesses both antigen multivalency and antigen‐specific immunostimulation properties, and induces a robust immune response. This simple vaccine initiated a potent immune response without requiring complex synthesis, allowing efficient and practical development of self‐adjuvanting vaccines.