Precise immunological evaluation rationalizes the design of a self-adjuvanting vaccine composed of glycan antigen, TLR1/2 ligand, and T-helper cell epitope

Chang, Tsung‐Che; Manabe, Yoshiyuki; Ito, Keita; Yamamoto, Ryuku; Kabayama, Kazuya; Ohshima, Shino; Kametani, Yoshie; Fujimoto, Yukari; Lin, Chun Cheng; Fukase, Koichi

doi:10.1039/d2ra03286d

Cited by 4 publications

(1 citation statement)

References 80 publications

(96 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The lipopeptide Pam 3 CSK 4 is one of the most widely employed TLR1/2 agonists and has been extensively applied in various antitumor and antiviral vaccines as adjuvant for immune response augmentation. − Furthermore, previous studies have also reported that covalently linking TLR1/2 agonists to peptide or protein antigens significantly enhanced their immunogenicity, thereby eliciting potent antigen-specific immune responses. − Additionally, lipidation is a post-translational modification with significant clinical relevance, especially in the drug development and design of therapeutic agents . In vaccine design, lipid modification of peptides or protein antigens can effectively facilitate the self-assembly and aggregation of antigens, thereby enhancing their uptake by antigen-presenting cells, consequently strengthening antigen-specific immune responses.…”

Section: Introductionmentioning

confidence: 99%

Multifunctional Lipidated Protein Carrier with a Built-In Adjuvant as a Universal Vaccine Platform Potently Elevates Immunogenicity of Weak Antigens

Zhou,

Zhang,

Wen

et al. 2024

J. Med. Chem.

View full text Add to dashboard Cite

Weak antigens represented by MUC1 are poorly immunogenic, which greatly constrains the development of relevant vaccines. Herein, we developed a multifunctional lipidated protein as a carrier, in which the TLR1/2 agonist Pam 3 CSK 4 was conjugated to the N-terminus of MUC1-loaded carrier protein BSA through pyridoxal 5′phosphate-mediated transamination reaction. The resulting Pam 3 CSK 4 − BSA-MUC1 conjugate was subsequently incorporated into liposomes, which biomimics the membrane structure of tumor cells. The results indicated that this lipidated protein carrier significantly enhanced antigen uptake by APCs and obviously augmented the retention of the vaccine at the injection site. Compared with the BSA-MUC1 and BSA-MUC1 + Pam 3 CSK 4 groups, Pam 3 CSK 4 −BSA-MUC1 evoked 22-and 11-fold increases in MUC1-specific IgG titers. Importantly, Pam 3 CSK 4 −BSA-MUC1 elicited robust cellular immunity and significantly inhibited tumor growth. This is the first time that lipidated protein was constructed to enhance antigen immunogenicity, and this universal carrier platform exhibits promise for utilization in various vaccines, holding the potential for further clinical application.

show abstract

Section: Introductionmentioning

confidence: 99%

Multifunctional Lipidated Protein Carrier with a Built-In Adjuvant as a Universal Vaccine Platform Potently Elevates Immunogenicity of Weak Antigens

Zhou,

Zhang,

Wen

et al. 2024

J. Med. Chem.

View full text Add to dashboard Cite

show abstract

A multivalent CD44 glycoconjugate vaccine candidate for cancer immunotherapy

Freitas,

Miranda,

Ferreira

et al. 2024

Journal of Controlled Release

View full text Add to dashboard Cite

A Sweet Warning: Mucin-Type O-Glycans in Cancer

Zhang

Sun

Lei³

et al. 2022

Cells

View full text Add to dashboard Cite

Glycosylation is a common post-translational modification process of proteins. Mucin-type O-glycosylation is an O-glycosylation that starts from protein serine/threonine residues. Normally, it is involved in the normal development and differentiation of cells and tissues, abnormal glycosylation can lead to a variety of diseases, especially cancer. This paper reviews the normal biosynthesis of mucin-type O-glycans and their role in the maintenance of body health, followed by the mechanisms of abnormal mucin-type O-glycosylation in the development of diseases, especially tumors, including the effects of Tn, STn, T antigen, and different glycosyltransferases, with special emphasis on their role in the development of gastric cancer. Finally, tumor immunotherapy targeting mucin-type O-glycans was discussed.

show abstract

Precise immunological evaluation rationalizes the design of a self-adjuvanting vaccine composed of glycan antigen, TLR1/2 ligand, and T-helper cell epitope

Abstract: Detailed analysis of a three-component self-adjuvanting vaccine revealed that conjugate vaccines can be designed to achieve the desired immune responsesviabottom-up construction of the necessary immune elements.

Cited by 4 publications

References 80 publications

Multifunctional Lipidated Protein Carrier with a Built-In Adjuvant as a Universal Vaccine Platform Potently Elevates Immunogenicity of Weak Antigens

Multifunctional Lipidated Protein Carrier with a Built-In Adjuvant as a Universal Vaccine Platform Potently Elevates Immunogenicity of Weak Antigens

A multivalent CD44 glycoconjugate vaccine candidate for cancer immunotherapy

A Sweet Warning: Mucin-Type O-Glycans in Cancer

Contact Info

Product

Resources

About