A biotin-avidin-system-based virus-mimicking nanovaccine for tumor immunotherapy

Virus is a nanosized pathogen and mainly composed of viral protein and nucleic acids. Under the pressure of long-term selection, mammals have gradually evolved effective immune mechanisms to defend themselves against viruses. In addition to recognizing viral proteins, immune system can also respond to viral sequence-specific nucleic acids, including CpG ODN, single- and double- strand RNA, and thereby enhancing the ability to remove infected viruses. Inspired by these immune mechanisms, we have attempted to develop a tracing virus-mimicking nanovaccine for tumor immunotherapy. This nanovaccine mainly consists of nucleic acids (CpG ODN), proteins (including tumor-associated antigen, and neutravidin (nAvidin) as skeleton materials for constructing nanovaccine and carriers for loading tumor-associated antigen and CpG ODN), and the dye molecules for assembling nAvidin to form nanoparticles comparable in size to viruses and tracing the vaccine in vitro and in vivo. The as-prepared nanovaccine efficiently induces the maturation of dendritic cell, the enhancement of antigen cross-presentation ability, and amplification of cytokine production in vitro. Furthermore, in vivo analysis clearly shows that it targets lymph nodes, successfully presents antigens to generate tumor-antigen-specific CD8+ T cells and induces a Th1-biased immune response. Most notably, this virus-mimicking nanovaccine significantly inhibits the growth of antigen-expressed tumor and prolongs the survival time of the antigen-expressed tumor bearing mice.