Antigen epitope-TLR7/8a conjugate as self-assembled carrier-free nanovaccine for personalized immunotherapy

Abstract

Epitope-based vaccine is a promising personalized cancer immunotherapy; however, a simple and effective approach for its bulk manufacturing is challenging. Current vaccination strategies complicate the process by introducing unnecessary components such as additional delivery carriers, and assembly units. Herein, a type of toll-like receptor 7/8 agonist-epitope conjugate (termed as TLR7/8a-epitope) has been developed as a self-assembled and carrier-free nano vaccine platform, which effectively introduces the antigen and adjuvant with maximum precision, resulting in significantly enhanced dendritic cells (DCs) activation through the MyD88-dependent TLR signaling pathway. TLR7/8a-epitope nanovaccine can prolong the local retention and increase drainage efficiency into the lymph node, eliciting a significantly higher level of CD8 T-cell immunity than those of conventional vaccine formulations. The immunization with TLR7/8a-epitope nanovaccine in mice can not only resist the invasion of B16 cancer cells, but also produce significant therapeutic effects against established B16 melanoma tumors. Therefore, the TLR7/8a-epitope nanovaccine, developed by the direct chemical conjugation of antigen peptide with immunoadjuvant, has great advantages of clear and leanest compositions, controllable and definite preparation process, and remarkable therapeutic effects, representing a new appraoch for personalized cancer immunotherapy. Statement of significanceHerein, a kind of toll-like receptor 7/8 agonist-epitope conjugate was developed and spontaneously self-assemble into nanostructure in aqueous solution without the use of any additional constituents, which can be termed as unique carrier-free nanovaccine platform, providing effectually the leanest vaccine components with maximally and precisely loading of antigen and adjuvant.Significantly, the nanovaccine augmented the immunogenicity of antigenic peptide by increasing DCs activation through MyD88-mediated TLR signaling pathways and promoting T-cell priming. Moreover, nanovaccines could prolong the local retention and further increase the efficiency of drainage into dLNs, which was contributing to efficient initiation of epitope-specific memory and effector T-cell immune responses, leading to effective prophylactic and therapeutic antitumor effects.