One-pot generating subunit vaccine with high encapsulating efficiency and fast lysosome escape for potent cellular immune response.

Utilizing nanoparticles to deliver subunit vaccine is considered to be a promising strategy to improve immune response. However, currently reported systems suffered from one or more points: e.g., delicate design on molecular structures and elaborate synthesis process, low antigen and/or adjuvant encapsulation efficiency, involvement of toxic materials, and denature of bioactivity of antigen and/or adjuvant. To address these issues, here, for the first time, we developed a one-pot method to produce subunit vaccine by using hexahistidine metal assembly (HmA) to co-deliver tumor-associated antigens (GP100) and adjuvant (CpG). The generation of subunit vaccine (GP100@HmA and (GP100+CpG)@HmA) were detailly characterized by various techniques, including dynamic scatter, SEM, TEM, UV-vis, agarose gel electrophoresis, etc. HmA displayed high efficiency on encapsulating both subunits (GP100 and CpG) under mild conditions, and the generated subunit vaccine showed pH dependent release profile of loaded subunits. In the in vitro tests, such subunit vaccine behaved quick endocytosis into immune cells, fast endo/lysosomes escape, inducing maturation of antigen presentative cells and stimulating potent cellular immune response. These results suggested that HmA be a robust platform for fabricating subunit vaccine, with immense potential to immunotherapy of various diseases.