Investigations On Antitumor Effects Of DNA Vaccinations And Antigen Processing And Presentation Of YIC In Dendritic Cells

Compared to traditional vaccines, DNA vaccine stimulates both potent humoral and cellular immune responses. DNA vaccine also offers advantages in terms of their design, production and safety. These merits promote DNA vaccines to become one of the hottest areas in vaccine research and development. Dendritic cells (DCs) are the most powerful antigen presenting cells, which play an important role in innate immunity and adaptive immunity. The primary objectives of this study were to develop novel antitumor DNA vaccine and preliminarily investigate the mechanism of antigen and antibody immune-complex (YIC) antigen processing and presentation in DC.The p42.3gene was recently identified and characterized as having tumor-specific and mitosis phase-dependent expression in various types of cancer. This suggested that p42.3antigen could be used as a target for vaccines against various cancers. In this study, we immunized C57BL/6mice with a DNA vaccine encoding p42.3via intramuscular injections with an electroporation, either before or after challenged with tumor B16F10cells. Vaccinations with pcDNA3-p42.3induced some degrees of antitumor effects both therapeutically and prophylactically, as evaluated by the inhibition of tumor growth and progression in tumor weight. Immunized mice showed a high level of specific cytotoxic activity against the p42.3protein in vivo correlated with the activated CD8+T cells secreting IFN-y, perforin, and granzyme B in response to stimulation with the antigen in vitro. Thus, this study presents evidence that the use of DNA vaccination against novel tumor target p42.3as a promising antitumor modality.Disease caused by the hepatitis B virus (HBV) is a major global health problem. Although the prophylactic HBV vaccine significantly reduced the rate of HBV infection, diseases associated with HBV infection posed a great threat to human health. Wen YM.et al have previously conducted a series of clinical tries, in which immunization of yeast-derived HBsAg-anti-HBs complexes (YIC) has been shown to decrease the HBV load and to convert HBeAg to antibody to HBeAg (anti-HBe) in a subset of chronic hepatitis B patients. In this study, we performed an in-depth analysis of the internalization and endocytic pathway of HBIG-bound HBsAg (IC) and found that antigen presenting cells internalized the HBsAg complexed to HBIG via the Fcγ receptor (FcyR) and thereby leading to modified antigen processing and presentation preferable to cross-presentation. In addition, IC-loaded DC induced more potent T cells in mice in vivo. These results have laid some ground for our knowledge on the IC processing inside of DCs and allowed us to further optimize the effect of this therapeutic vaccine for chronic hepatitis B patients.