Engineered virus-hunter vaccine overcomes HBV immune tolerance

Area of Science:

• Immunology
• Vaccinology
• Hepatology

Background:

• Chronic hepatitis B virus (HBV) infection affects millions globally, leading to severe liver disease.
• Current treatments offer limited functional cure rates, necessitating innovative therapeutic approaches.

Purpose of the Study:

• To develop a 'virus-hunter vaccine' platform (SHARP) to induce anti-HBV immunity.
• To achieve a durable functional cure for chronic HBV infection by reprogramming dendritic cells (DCs).

Main Methods:

• Engineered the SHARP platform using a bispecific antibody targeting HBsAg and DEC-205, conjugated with TLR7/8 agonists.
• Assessed therapeutic efficacy and immunological mechanisms in chronic HBV carrier mice.

Main Results:

• SHARP enhanced DC phagocytosis, maturation, and antigen presentation.
• The lead candidate, SHARP-D265A, demonstrated superior efficacy, reversing the tolerogenic microenvironment.
• Achieved durable viral control with undetectable HBsAg and sustained anti-HBsAg immune memory.

Conclusions:

• The SHARP vaccine strategy overcomes immune tolerance in chronic HBV infection.
• Offers a novel therapeutic approach for chronic HBV and other immune-tolerant diseases.