Synthetic DNA immunogen encoding hepatitis B core antigen drives immune response in liver

Area of Science:

• Immunology
• Hepatology
• Vaccinology

Background:

• Hepatitis B virus (HBV) infection is a global health crisis, particularly in Asia and sub-Saharan Africa.
• A quarter billion people are chronically infected, facing risks of liver cancer.
• Effective vaccines are needed to combat diverse HBV genotypes and induce protective immunity.

Purpose of the Study:

• To evaluate a synthetic DNA vaccine encoding a consensus HBV core antigen (HBcAg) from genotypes A-E.
• To determine the vaccine's ability to induce liver-specific immune responses.
• To assess the protective efficacy against HBV infection models.

Main Methods:

• Intramuscular vaccination of mice with a DNA vaccine encoding a consensus HBcAg.
• Assessment of systemic and liver-specific T cell and antibody responses.
• Evaluation of cytotoxic T lymphocyte activity against HBV-infected cells.
• Testing vaccine efficacy in a hydrodynamic liver transfection model.

Main Results:

• The DNA vaccine induced robust antigen-specific T cell and high-titer antibody responses, both systemically and within the liver.
• Vaccinated mice exhibited strong cytotoxic responses capable of eliminating HBV-coated target cells.
• The vaccine-induced immunity conferred protection against HBcAg plasmid-induced liver transfection.

Conclusions:

• Synthetic DNA vaccination targeting HBcAg can effectively generate peripheral immune responses that are recruited to the liver.
• This strategy offers a promising avenue for developing prophylactic vaccines and immunotherapies for liver diseases like hepatitis B.
• The findings highlight the potential of inducing liver-directed immunity for combating viral hepatitis.