One-Pot Generating Subunit Vaccine with High Encapsulating Efficiency and Fast Lysosome Escape for Potent Cellular Immune Response

Abstract

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, for example, delicate design on molecular structures and elaborate synthesis process, low antigen and/or adjuvant encapsulation efficiency, involvement of toxic materials, and denaturing of bioactivity of antigen and/or adjuvant. To address these issues, here, for the first time, we developed a onepot method to produce a subunit vaccine by using hexa-histidine metal assembly (HmA) to codeliver tumor-associated antigens (GP100, a peptide KTWGQYWQV) and adjuvant (CpG). The generation of subunit vaccines was detailedly characterized by various techniques, including dynamic scatter, scanning electron microscopy, transmission electron microscopy, UV−visible spectroscopy, agarose gel electrophoresis, etc. HmA displayed high efficiency on encapsulating both subunits (GP100 and CpG) under mild conditions, and the generated subunit vaccine showed a pH-dependent release profile of loaded subunits. In the cellular tests, these subunit vaccines behaved with a quick endocytosis into immune cells and a fast endo/lysosomes escape, inducing maturation of antigen presentative cells and stimulating a potent cellular immune response. These results suggested that HmA is a robust platform for fabricating subunit vaccine, with immense potential for the immunotherapy of various diseases.

Synthesis of a crystalline zeolitic imidazole framework-8 nano-coating on single environment-sensitive viral particles for enhanced immune responses

“…[5][6][7][8][9] Since the rst report on the construction of MOF-based vaccine synthesized by biomimetic mineralized growth of ZIF-8 onto the surface of ovalbumin (OVA) and attaching the cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODNs) in/on ZIF-8, the exploration of ZIF-8 in the delivery of vaccine antigens has been attracting more attention. [10][11][12][13][14][15] Research efforts have demonstrated that in addition to the typical advantages of ZIF-8 in drug delivery, the MOF-based vaccine platform also exhibited adjuvant effects by stabilizing antigens, 11 promoting antigen presentation, 10 codelivering other adjuvants 14,16 and inducing multiple immune responses. 15 Encouraged by the successes in the synthesis and delivery of OVA@ZIF-8 vaccine, researchers started trying to synthesize viral vaccines by encapsulating various types of viral antigens, including virus-like particles, live viruses, and viral vectors into ZIF-8.…”

ROS-responsive MSC-derived Exosome Mimetics Carrying MHY1485 Alleviate Renal Ischemia Reperfusion Injury through Multiple Mechanisms

“…The red fluorescence around the nucleus suggested that MTM-EM had been internalized by cells, confirming the successful uptake. Notably, some of the red fluorescence did not overlap with green lysosomes, indicating that MTM-EM partially escaped the degradation of lysosomes, further confirming the effective utilization of MTM-EM by TCMK-1 …”

Advances in Immunomodulatory MOFs for Biomedical Applications

“…[50] A "Trojan Horse"-like aluminum-based MOF was also developed as an oral administration vaccine, which showed resistance to highly acidic and degradative gastrointestinal conditions and further mediated long-lasting sIgA and IgG production. [84] Besides ZIF-8 which is commonly used, other kinds of MOFs have also been developed as vaccine vehicles including MIL-101-Fe-NH 2 , [49] amino-functionalized zirconium-based MOF (UiO-AM), [85] hexahistidine metal assembly (HmA), [86] and 𝛾-cyclodextrin MOF. [87] (Table 1)…”