Alum Adjuvant and Built-in TLR7 Agonist Synergistically Enhance Anti-MUC1 Immune Responses for Cancer Vaccine

Abstract

The tumor-associated antigen mucin 1 (MUC1) is an attractive target of antitumor vaccine, but its weak immunogenicity is a big challenge for the development of vaccine. In order to enhance immune responses against MUC1, herein, we conjugated small molecular toll-like receptor 7 agonist (TLR7a) to carrier protein BSA via MUC1 glycopeptide to form a three-component conjugate (BSA-MUC1-TLR7a). Furthermore, we combined the three-component conjugate with Alum adjuvant to explore their synergistic effects. The immunological studies indicated that Alum adjuvant and built-in TLR7a synergistically enhanced anti-MUC1 antibody responses and showed Th1-biased immune responses. Meanwhile, antibodies elicited by the vaccine candidate effectively recognized tumor cells and induced complement-dependent cytotoxicity. In addition, Alum adjuvant and built-in TLR7a synergistically enhanced MUC1 glycopeptide-specific memory CD8+ T-cell immune responses. More importantly, the vaccine with the binary adjuvant can significantly inhibit tumor growth and prolong the survival time of mice in the tumor challenge experiment. This novel vaccine construct provides an effective strategy to develop antitumor vaccines.

A protein vaccine with Alum/c-GAMP/poly(I:C) rapidly boosts robust immunity against SARS-CoV-2 and variants of concern

“…The pattern of IgG antibody subclasses is an indicator of the Th1 and Th2 immune responses. 35 Ternary adjuvant vaccine increased the IgG1 antibody titers (up to 2.3 Â 10 6 ) by 10-fold, compared with the S1 + Alum group (Fig. 2c).…”

Self-Adjuvanting Protein Vaccine Conjugated with a Novel Synthetic TLR4 Agonist on Virus-Like Liposome Induces Potent Immunity against SARS-CoV-2

“…In conventional protein-based vaccines (Figure A), adjuvants are usually physically mixed with antigens as external immune stimulators, − but this could not guarantee the codelivery of adjuvant and antigen to the same antigen-presenting cell (APC) . In contrast, conjugating adjuvants on antigens leads to not only antigen presentation to T cells, but also APC activation at the same time and same location, and antigens with built-in adjuvants have been previously proved to be highly immunogenic. − Moreover, the adjuvant–antigen conjugation strategy has been successfully applied to develop an effective COVID-19 candidate vaccine in our previous work. , …”

Breast Cancer Vaccine Containing a Novel Toll-like Receptor 7 Agonist and an Aluminum Adjuvant Exerts Antitumor Effects

“…MUC1 contains a variable number of tandem repeat (VNTR) sequence of twenty amino acids, and five potential O-glycosylation sites are located on the threonine and serine residues of each repeat [ 10 , 11 ]. The peptides from the VNTR sequence are often used as the antigens for tumor vaccines targeting MUC1 [ 12 ]. A tumor vaccine has been constructed by covalent attachment of an MUC1 glycopeptide and a T-helper epitope, inducing both humoral and cellular immune responses [ 13 ].…”