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

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 Pam3CSK4 was conjugated to
the N-terminus of MUC1-loaded carrier protein BSA
through pyridoxal 5′-phosphate-mediated transamination reaction.
The resulting Pam3CSK4–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 + Pam3CSK4 groups, Pam3CSK4–BSA-MUC1 evoked
22- and 11-fold increases in MUC1-specific IgG titers. Importantly,
Pam3CSK4–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.