Correlation between antigen density on the surface of hepatitis B virus core protein virus-like particles and their antibody response

Abstract:

[Objective] To better understand how antigen density on the surface of hepatitis B virus core protein (HBc) virus-like particles (VLPs) affects their antibody response, we generated HBc VLPs with different antigen densities, and tested their antibody response in mice.[Methods] First, we prepared the recombinant antigen domain 4 (AD-4) of human cytomegalovirus (HCMV) as a model antigen, which contains three glycine molecules at its N-terminus, for Sortase A-mediated ligation onto the HBc VLPs. Displaying different densities of antigens onto the surface of VLPs was achieved by using a serial diluted recombinant AD-4 in ligation reactions. After that, HBc-AD-4 VLPs with different antigen densities were applied to 6-8 weeks old BALB/c mice. Each group was inoculated three times at 2-week intervals and the AD-4-specific IgG was detected by indirect ELISA.[Results] When the reaction concentration ratio between HBc and AD-4 is 1:0.5, which HBc surface antigen density is 44.4%, VLPs couldn't induce a high antibody titer. When the reaction concentration ratio between HBc and AD-4 is 1:1, which HBc surface antigen density is 64.2%, VLPs could induce similar highest humoral immune response compared to 100% antigen density HBc VLPs. When HBc surface antigen density is greater than 64.2%, no further enhancement of antibody response was observed by further increasing the antigen density.[Conclusion] In conclusion, we found that antigen density on HBc VLPs is positively correlated with the antibody response. However, it reaches a peak at 64% antigen density, and no further enhancement of antibody response was observed by further increasing the antigen density.