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

Taku Aiga; Yoshiyuki Manabe; Keita Ito; Tsung-Che Chang; Kazuya Kabayama; Shino Ohshima; Yoshie Kametani; Ayane Miura; Hiroto Furukawa; Hiroshi Inaba; Kazunori Matsuura; Koichi Fukase

doi:10.1002/anie.202007999

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

Angew Chem Int Ed Engl. 2020 Sep 28;59(40):17705-17711. doi: 10.1002/anie.202007999. Epub 2020 Aug 11.

Authors

Taku Aiga¹, Yoshiyuki Manabe^{1

2}, Keita Ito^{1

2}, Tsung-Che Chang¹, Kazuya Kabayama^{1

2}, Shino Ohshima³, Yoshie Kametani³, Ayane Miura¹, Hiroto Furukawa⁴, Hiroshi Inaba⁴, Kazunori Matsuura⁴, Koichi Fukase^{1

2}

Affiliations

¹ Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka, 560-0043, Japan.
² 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.

PMID: 32583549
DOI: 10.1002/anie.202007999

Abstract

Co-assembling vaccines composed of a lipidated HER2-derived antigenic CH401 peptide and either a lipophilic adjuvant, Pam₃ CSK₄ , 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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adjuvants, Immunologic / chemistry*
Animals
Antigens / chemistry
Antigens / immunology
Breast Neoplasms / drug therapy*
Breast Neoplasms / pathology
Cancer Vaccines / chemistry
Cancer Vaccines / therapeutic use*
Female
Galactosylceramides / chemistry
Humans
Immunoglobulin G / blood
Immunoglobulin M / blood
Immunoglobulin M / immunology
Immunoglobulin M / metabolism
Lipopeptides / chemistry
Mice
Mice, Inbred BALB C
Peptides / chemistry
Peptides / immunology*

Substances

Adjuvants, Immunologic
Antigens
Cancer Vaccines
Galactosylceramides
Immunoglobulin G
Immunoglobulin M
Lipopeptides
Pam(3)CSK(4) peptide
Peptides
alpha-galactosylceramide