Impacts of the G145R Mutation on the Structure and Immunogenic Activity of the Hepatitis B Surface Antigen: A Computational Analysis

Conclusions: These data will be beneficial for designing more advanced antibodies for the recognition of the HBsAg in diagnostics. In addition, the results of this study may assist in the design or development of a more effective hepatitis B vaccine.,Results: The G145R mutation causes a considerable reduction in the immunogenic activity of the HBsAg through a local change in the conformation of the HBsAg antigenic loops. This mutation inserts a new β-strand in the “a” determinant region of the HBsAg, leading to a reduced binding affinity to its monoclonal antibody, MAb12. The G145R mutation also increased the compactness and stability of the HBsAg by enhancing the rigidity of the “a” determinant.,Objectives: The present study analyzed the effects of the G145R mutation on the structure and immunogenic activity of the HBsAg.,Materials and Methods: The three-dimensional (3D) structure of the HBsAg for both the wild-type and the G145R mutant were predicted and refined using several web tools. After quantitative evaluations, the effects of the G145R mutation on the secondary and 3D structures of the HBsAg were investigated. In parallel, the immunogenic activity of the wild-type and mutant HBsAg was also analyzed using a ClusPro docking server as well as the IEDB web tool. Further analyses were performed via molecular dynamics (MD) simulations using the GROMACS v5.0.2 simulation package.,Background: Vaccine-escaped hepatitis B virus (HBV) mutations occur within the “a”...
Source: Hepatitis Monthly - Category: Infectious Diseases Source Type: research