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The highly glycosylated mucin 1 (MUC1) serves as a promising target for cancer vaccines. However, the weak immunogenicity of MUC1 greatly impedes its application. Here, we covalently linked a MUC1 glycopeptide to carrier protein bovine serum albumin (BSA), and the resulting BSA-MUC1 conjugate was integrated with a ternary adjuvant system comprising TLR3 agonist poly(I:C), STING agonist c-GAMP, and Alum adjuvant. Compared to adjuvant-free and Alum-adjuvanted groups, the ternary adjuvant group induced 18.3- and 10.9-fold increases in MUC1-specific IgG titers, and effectively suppressed tumor growth. These findings may propose a straightforward yet highly effective strategy for designing vaccines, offering promising prospects in cancer treatment. [ABSTRACT FROM AUTHOR]

Developing a novel and potent adjuvant with great biocompatibility for immune response augmentation is of great significance to enhance vaccine efficacy. In this work, we prepared a long-term stable, pH-sensitive, and biodegradable Mn 3 (PO 4 ) 2 ·3H 2 O nanoparticle (nano-MnP) by simply mixing MnCl 2 /NaH 2 PO 4 /Na 2 HPO 4 solution for the first time and employed it as an immune stimulant in the bivalent COVID-19 protein vaccine comprised of wild-type S1 (S1-WT) and Omicron S1 (S1-Omicron) proteins as antigens to elicit a broad-spectrum immunity. The biological experiments indicated that the nano-MnP could effectively activate antigen-presenting cells through the cGAS-STING pathway. Compared with the conventional Alum-adjuvanted group, the nano-MnP-adjuvanted bivalent vaccine elicited approximately 7- and 8-fold increases in IgG antibody titers and antigen-specific IFN-γ secreting T cells, respectively. Importantly, antisera of the nano-MnP-adjuvanted group could effectively cross-neutralize the SARS-CoV-2 and its five variants of concern (VOCs) including Alpha, Beta, Gamma, Delta, and Omicron, demonstrating that this bivalent vaccine based on S1-WT and S1-Omicron proteins is an effective vaccine design strategy to induce broad-spectrum immune responses. Collectively, this nano-MnP material may provide a novel and efficient adjuvant platform for various prophylactic and therapeutic vaccines and provide insights for the development of the next-generation manganese adjuvant.