More than two billion people are infected with hepatitis B virus (HBV), and 350 million become chronic HBV (CHB) carriers worldwide. Nearly one million people die from hepatitis B-related diseases every year. Persistent HBV infection still represents a substantial threat to the public health, despite the existence of effective prophylactic vaccines. There is an urgent need for effective treatment strategies to limit the enormous burden of viral hepatitis on global health.

In a recent study published in Hepatology, a research group led by Dr. FU Yangxin and Dr. PENG Hua from Institute of Biophysics of Chinese Academy of Sciences reported that the clinical CHB patients presented less immune tolerance to the preS1 of HBV large surface antigen. Using a well tolerate HBV carrier mice model by AAV-HBV1.3 infection, they proved that unlike the main toleragen HBsAg in CHB infection, the preS1 domain showed less tolerant.

To study whether targeting the weak tolerance of preS1 region could improve therapy gain, researchers explored vaccination with preS1 for HBV virions clearance. They found that this preS1 rather than HBsAg vaccination induced robust immune responses in the HBV carrier mice. The anti-preS1 induced in the model cleared HBV virions and could block HBV infection to hepatocytes. The vaccination even reduced the tolerized status of HBsAg, opening a therapeutic window for the host to respond to the HBsAg vaccine.

At last, by a sequential administration of antigenically distinct preS1 and HBsAg vaccines in HBV carrier mice, HBsAg-HBsAb serological conversion could finally be induced, which is a clinical indicator for CHB cure. These results would provide new target for therapeutic vaccine to the control of CHB.

The study was funded by Ministry of Science and Technology of China, National Natural Science Foundation of China and Chinese Academy of Sciences.