The role of CD4 T cells in therapeutic hepatitis B vaccine

Therapeutic vaccination is a promising, potentially curative treatment for chronic hepatitis B. However, which factors are essential for breaking immune tolerance in HBV carriers and determine a successful outcome remain unclear. Our study provides the first direct evidence that efficient priming of HBV-specific CD4 T cells determines the success of therapeutic hepatitis B vaccination in two preclinical HBV-carrier mouse models. Applying an optimal formulation of HBV antigens that allows activating CD4 and CD8 T cells during prime immunization provided the foundation for an antiviral effect of therapeutic vaccination, while depletion of CD4 T cells lead to a complete loss of vaccine-induced antiviral efficacy. Our findings provide important insights into the rational design of therapeutic vaccines to cure chronic hepatitis B.