DNA vaccines have a wide range of applications, with several potential advantages compared to other vaccine technologies for diseases. No DNA vaccine has yet been licensed in humans; however, a lot of effort has been made to enhance their potential as human vaccines and therapeutics. Finding an effective adjuvant is a strategy to improve the efficacy of DNA vaccines. We recently identified a fungal immunomodulatory protein Ling Zhi-8 (LZ-8) with stimulatory activity on dendritic cells (DCs) that significantly increases the efficacy of a cancer DNA vaccine in a preclinical tumor model, suggesting that LZ-8 may be a good candidate adjuvant for vaccine development. Here we discuss the possibility for applying LZ-8 to a cancer DNA vaccine for humans.

Protection of intestinal epithelial cells against inflammation by the fungal protein Ling Zhi-8 via maintaining the integrity of tight junctions.

Volvariella volvacea, also known as straw mushroom, is a common edible mushroom in Chinese cuisine. It contains many nutrients for human health. A fungal immunomodulatory protein (FIP) has been isolated from V. volvacea and named FIP-vvo. Although the regulatory effects of many FIPs on immunity have been identified, the impact of FIP-vvo in modulating dendritic cells (DCs), which play a key role to connect the innate and the adaptive immunity, is not known. In this study, we aim to study the effect of FIP-vvo on the DC maturation and function. We found that FIP-vvo slightly increased the generation of CD11c+ bone marrow-derived DC (BMDC). In addition, the surface expression of MHCII was promoted in BMDCs after the treatment of FIP-vvo, suggesting that FIP-vvo induces DC maturation. Furthermore, FIP-vvo enhanced the ability of BMDCs to activate antigen-specific T cell responses in vitro. In the in vivo study, the FIP-vvo treatment facilitated T cell response in lymph nodes. Therefore, for the first time, our data demonstrated that FIP-vvo promoted DC maturation and function and suggested that FIP-vvo could have benefits for human health by enhancing immunity.

CPT-11 (Irinotecan) remains an important chemotherapeutic agent against various solid tumors nowadays. Potential adverse effects, especially gastrointestinal toxicities, are the main limiting factor for its clinical utility. Ling Zhi-8 (LZ-8), a fungal immunomodulatory protein in Ganoderma lucidum mycelia, has potential for drug development due to its multiple bioactivities and functions. This study aimed to explore the influence of LZ-8 on CPT-11-treated IEC-6 cells in vitro and on mice with CPT-11-induced intestinal injury in vivo. The mechanism through which LZ-8 exerted its protective effects was also investigated. In the in vitro study, the viability and claudin-1 expression of IEC-6 cells decreased gradually with increasing concentrations of CPT-11, but LZ-8 treatment had no obvious influence on their viability, morphology, and claudin-1 expression. Pretreatment of LZ-8 significantly improved CPT-11-decreased cell viability and claudin-1 expression in IEC-6 cells. In mice with CPT-11-induced intestinal injury, LZ-8 treatment could ameliorate symptoms and mitigate intestinal damage. Meanwhile, LZ-8 restored claudin-1 expression in the intestinal membranes in CPT-11-treated mice. Collectively, our results demonstrated the protective effects of LZ-8 against CPT-11 damage in both IEC-6 cells and mice. LZ-8 can restore claudin-1 expression in intestinal cells following CPT-11 treatment, suggesting the role of claudin-1 in the scenario.