Expression and immune response to hepatitis C virus core DNA-based vaccine constructs

Area of Science:

• Immunology
• Virology
• Molecular Biology

Background:

• Hepatitis C virus (HCV) causes significant global liver disease, including cancer.
• Developing an effective HCV vaccine is challenging due to viral envelope variability.
• Cellular immune responses targeting viral structural proteins may be key to clearing persistent infections.

Purpose of the Study:

• To construct and evaluate DNA vectors expressing the conserved HCV core gene.
• To assess the cellular immune response, specifically cytotoxic T-lymphocyte (CTL) activity, generated by these vectors.
• To determine the potential of these constructs as antiviral agents.

Main Methods:

• Constructed DNA vectors (pHCV 2-2 and pHCV 4-2) expressing the HCV core gene.
• Transfected vectors into human and murine cell lines to assess core protein expression.
• Immunized BALB/c mice with vectors and evaluated humoral and CTL responses.
• Established a myeloma cell line expressing HCV core protein for in vivo and in vitro CTL assays.

Main Results:

• The pHCV 2-2 construct demonstrated higher intracellular expression of the HCV core protein.
• Immunization with HCV core DNA constructs induced low-level humoral responses.
• Significant CTL activity was observed in vivo, evidenced by reduced tumor size and weight in immunized mice.
• Splenocytes from immunized mice showed spontaneous CTL activity in in vitro assays.

Conclusions:

• Plasmid constructs expressing the HCV core gene effectively generate strong CTL activity.
• These findings highlight the potential of HCV core DNA vaccines as promising antiviral agents.
• Targeting the conserved HCV core protein via cellular immunity offers a potential strategy for combating HCV infection.