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

被引:23
作者
Aiga, Taku [1 ]
Manabe, Yoshiyuki [1 ,2 ]
Ito, Keita [1 ,2 ]
Chang, Tsung-Che [1 ]
Kabayama, Kazuya [1 ,2 ]
Ohshima, Shino [3 ]
Kametani, Yoshie [3 ]
Miura, Ayane [1 ]
Furukawa, Hiroto [4 ]
Inaba, Hiroshi [4 ]
Matsuura, Kazunori [4 ]
Fukase, Koichi [1 ,2 ]
机构
[1] Osaka Univ, Grad Sch Sci, Dept Chem, 1-1 Machikaneyama, Toyonaka, Osaka 5600043, Japan
[2] Osaka Univ, Project Res Ctr Fundamental Sci, Grad Sch Sci, Core Med & Sci Collaborat Res & Educ, 1-1 Machikaneyama, Toyonaka, Osaka 5600043, Japan
[3] Tokai Univ, Sch Med, Isehara, Kanagawa 2591193, Japan
[4] Tottori Univ, Ctr Res Green Sustainable Chem, Grad Sch Engn, Dept Chem & Biotechnol, 4-101 Koyama Minami, Tottori 6808552, Japan
关键词
adjuvants; antigens; cancer; peptides; self-assembly; ROBUST IMMUNE-RESPONSES; CLINICAL-TRIAL; ALPHA-GALACTOSYLCERAMIDES; LIPOPEPTIDE ADJUVANTS; MITOGENIC PRINCIPLE; CONJUGATE VACCINES; CELL-ACTIVATION; RECOGNITION; AGONIST; MUC1;
D O I
10.1002/anie.202007999
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Co-assembling vaccines composed of a lipidated HER2-derived antigenic CH401 peptide and either a lipophilic adjuvant, Pam(3)CSK(4), alpha-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, alpha-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.
引用
收藏
页码:17705 / 17711
页数:7
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