A potential therapeutic vaccine or method for chronic hepatitis B virus infection

What is it about?

Strong tolerance to hepatitis B virus (HBV) surface antigens limits the therapeutic effect of the conventional hepatitis B surface antigen (HBsAg) vaccination in both preclinical animal models and patients with chronic hepatitis B (CHB) infection. In contrast, we observed that clinical CHB patients presented less immune tolerance to the preS1 domain of HBV large surface antigen. To study whether targeting the weak tolerance of the preS1 region could improve therapy gain, we explored vaccination with the long peptide of the preS1 domain for HBV virions clearance. Our study showed that this preS1-polypeptide rather than HBsAg vaccination induced robust immune responses in HBV carrier mice. The anti-preS1 rapidly cleared HBV virions in vivo and blocked HBV infection to hepatocytes in vitro. Intriguingly, vaccination of preS1-polypeptide even reduced the tolerized status of HBsAg, opening a therapeutic window for the host to respond to the HBsAg vaccine. A sequential administration of antigenically distinct preS1-polypeptide and HBsAg vaccines in HBV carrier mice could finally induce HBsAg/hepatitis B surface antibody serological conversion and clear chronic HBV infection in carrier mice.

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Why is it important?

Persistent HBV infection still represents a substantial threat to public health, despite the existence of effective prophylactic vaccines. More than 2 billion people are infected with hepatitis B virus (HBV), and 350 million become chronic HBV carriers worldwide. Nearly one million people die from hepatitis B-related diseases every year. Thus, there remains an urgent need for effective treatment strategies to limit the enormous burden of viral hepatitis on global health.

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