Albumin and interferon-β fusion protein serves as an effective vaccine adjuvant to enhance antigen-specific CD8+T cell-mediated antitumor immunity

Background Type I interferons (IFN) promote dendritic cells maturation and subsequently enhance generation of antigen-specific CD8 +T cell for the control of tumor. Using type I interferons as an adjuvant to vaccination could prove to be a potent strategy. However, type I interferons have a short half-life. Albumin linked to a protein will prolong the half-life of the linked protein. Methods In this study, we explored the fusion of albumin to IFN beta (Alb-IFN beta) for its functional activity both in vitro and in vivo. We determined the half-life of Alb-IFN beta following treatment in the serum, tumor, and tumor draining lymph nodes in both wild type and FcRn knockout mice. We characterized the ability of Alb-IFN beta to enhance antigen-specific CD8+ T cells using ovalbumin (OVA) or human papillomavirus (HPV) E7 long peptides. Next, we evaluated the therapeutic antitumor effect of coadministration of AIbIFN beta with antigenic peptides against HPVE7 expressing tumor and the treatment's ability to generate HPVE7 antigen specific CD8+ T cells. The contribution of the antitumor effect by lymphocytes was also examined by an antibody depletion experiment. The ability of Alb-IFN beta to serve as an adjuvant was tested using clinical grade therapeutic protein-based HPV vaccine, TACIN. Results Alb-IFN beta retains biological function and does not alter the biological activity of IFN beta. In addition, Alb-IFN beta extends half-life of IFN beta in serum, lymph nodes and tumor. The coadministration of Alb-IFN beta with OVA or HPVE7 antigenic peptides enhances antigen-specific CD8 +T cell immunity, and in a TC-1 tumor model results in a significant therapeutic antitumor effect. We found that CD8 +T cells and dendritic cells, but not CD4 +T cells, are important for the observed antitumor therapeutic effect mediated by Alb-IFN beta. Finally, Alb-IFN beta served as a potent adjuvant for TA-CIN for the treatment of HPV antigen expressing tumors. Conclusions Overall, Alb-IFN beta serves as a potent adjuvant for enhancement of strong antigen-specific CD8 +T cell antitumor immunity, reduction of tumor burden, and increase in overall survival. Alb-IFN beta potentially can serve as an innovative adjuvant for the development of vaccines for the control of infectious disease and cancer.

Automated summary

The fusion of albumin to IFN beta (Alb-IFN beta) enhances immune function, prolongs the half-life of IFN beta, and has a significant antitumor effect. Alb-IFN beta can serve as an innovative adjuvant for vaccine development.