Tumor cells are rich in antigens, which provide a reliable antigen library for the design of personalized vaccines. However, an effective tumor vaccine vector that can efficiently deliver antigens to lymphoid organs to stimulate strong CD8 + cytotoxic T-lymphocyte immune response is still lacking. Here we designed a dual-antigen delivery system based on hepatitis B virus core antigen virus-like particles (HBc VLPs). We first confirmed that different antigen-loaded HBc VLP monomers could be assembled into nanoparticles (hybrid VLPs). Hybrid VLPs could slightly enhance bone marrow-derived dendritic cell maturation in vitro. Strikingly, hybrid VLPs could generate antigen-specific antitumor immunity and innate immunity in vivo which could significantly inhibit tumor growth or metastatic formation in a subcutaneous tumor or lung metastatic tumor model, respectively. Moreover, dual-epitope vaccination generated enhanced T-cell responses that potently inhibited tumor growth and metastatic formation. Together, this study provides a new powerful concept for cancer immunotherapy and suggests a novel design for VLP-based personalized nanomedicine.
Hepatitis B virus (HBV) can be present in the circulating blood either as free virus or as a virion-immunoglobulin (Ig) complex. Presently, it remains unclear what specific role each Ig plays in the clearance of HBV. In this study, a novel method that combined immuno-capture and polymerase chain reaction (PCR) amplification was used for detecting and distinguishing different HBV-Ig complexes. Three isotypes of Ig (IgM, IgG and IgA) bound to HBV were detected in the four clinically defined stages of HBV infection in 108 patients. The results showed that all the three isotypes of Ig could bind to HBV, and the patterns of HBV-Ig complexes varied according to disease categories. Interestingly, the frequency of HBV DNA-Ig complexes in hepatitis B e antigen (HBeAg)-positive patients was significantly lower than that in HBeAg-negative patients. All the data suggest that the three isotypes of HBV DNA-Ig circulating immune complex (CIC) may have different biological meanings. In summary, HBV bound to an antibody is a common feature of hepatitis B, and immuno-capture PCR is a valuable method for the analysis of the composition of the immune complexes. The detection of HBV-Ig complexes may provide new and valuable insights into HBV pathogenesis.
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