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.

中文翻译：

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具有内置佐剂的多功能脂化蛋白载体作为通用疫苗平台可有效提高弱抗原的免疫原性

以MUC1为代表的弱抗原免疫原性较差，极大地制约了相关疫苗的研发。在此，我们开发了一种多功能脂质化蛋白作为载体，其中TLR1/2激动剂Pam ₃ CSK ₄通过吡哆醛5'-磷酸介导的转氨反应与MUC1负载的载体蛋白BSA的N端缀合。随后将所得的 Pam ₃ CSK ₄ –BSA-MUC1 缀合物掺入脂质体中，从而仿生肿瘤细胞的膜结构。结果表明，这种脂化蛋白载体显着增强了APC对抗原的摄取，并明显增强了疫苗在注射部位的保留。与 BSA-MUC1 和 BSA-MUC1 + Pam ₃ CSK ₄组相比，Pam ₃ CSK ₄ –BSA-MUC1 引起 MUC1 特异性 IgG 滴度增加 22 倍和 11 倍。重要的是，Pam ₃ CSK ₄ –BSA-MUC1 能够引发强大的细胞免疫并显着抑制肿瘤生长。这是首次构建脂化蛋白来增强抗原免疫原性，这种通用载体平台有望在各种疫苗中使用，并具有进一步临床应用的潜力。