A new strategy for "sandwich therapy" or functional cure for hepatitis B

Recently, Yuan Zhenghong, a member of the Chinese Academy of Engineering and director of the Medical Molecular Virology Laboratory at Fudan University's Shanghai School of Medicine, and He Tianlei, among others, confirmed the feasibility of "sandwich therapy" in animal models of chronic hepatitis B infection. The findings were published online at EBioMedicine.
B is one of the most prevalent infectious diseases in China. It is estimated that there are about 90 million chronic hepatitis B virus infections in China, accounting for one-third of the global total (260 million). Chronic infection of hepatitis B virus is a common cause of liver disease, and the proportion of patients with primary liver cancer in China caused by hepatitis B virus infection is as high as 80%. However, nucleoside drugs and interferons currently approved for chronic hepatitis B treatment can only inhibit viral replication and do not effectively remove hepatitis B surface antigens. In view of this, how to effectively reduce or even remove the surface antigen of hepatitis B in patients with chronic hepatitis B, to achieve the functional cure of chronic hepatitis B, has become a hot research topic of scholars at home and abroad.
Three years ago, Wen Yumei innovatively put forward a "sandwich therapy" that promises a functional cure for chronic hepatitis B, that is, antiviral small molecule drugs and monoclonal antibodies against hepatitis B surface antigens, so that the virus and hepatitis B surface antigens in a short period of time reduced, thus opening an immune window, and then use preventive or therapeutic vaccines for active immunity, inducing patients to produce their own antibodies against hepatitis B surface antigens, in order to achieve functional cure of chronic hepatitis B. In a model of chronic hepatitis B mice injected intravenously at high pressure tail, the researchers used the self-developed powerful anti-hepatitis B all-human source and antibody G12. The study found that a single dose of G12 antibody therapy can be very effective in mice circulating hepatitis B surface antigen level significantly reduced by nearly a month, and a total of three stitches per month G12 treatment can effectively remove hepatitis B mice serum surface antigen, but also promote the active production of hepatitis B surface antibodies in mice. Control groups that used unrelated antibodies or commercialized hepatitis B immunoglobulin (HBIG) had no therapeutic effect.
based on G12 antibodies that quickly and effectively remove surface antigens from hepatitis B, the team further studied the therapeutic effects of sandwich therapy in chronic hepatitis B mice based on adenovirus (AAV/HBV1.2) infections. The antiviral drug tynofoviride (TDF) was given throughout the course, and G12 antibodies were injected into mice after 5 days, forming a "window period" in which serum surface antigens and viral DNA were lower, and then the hepatitis B therapeutic vaccine (mYIC) was injected through the abdominal cavity to activate the host's active immune response. The treatment of three G12 antibodies and mYIC vaccine not only effectively reduced the expression of hepatitis B virus antigens in the serum and liver of chronic hepatitis B mice, but also activated the body fluid immune response in the bone marrow of mice that actively produced anti-hepatitis B surface antigen antibodies.
same time, in the post-treatment mouse immunopathology study also found that "sandwich therapy" effectively activated the chronic hepatitis B mice liver in place of the antiviral cell immune response.
Yuan Zhenghong said the study showed that the use of antiviral drugs combined with highly effective hepatitis B neutral antibodies, reduce the patient's virus and antigen to low levels, and then apply active and specific immunotherapy ("sandwich therapy"), will be effective in achieving a functional cure of chronic hepatitis B. He hoped that this simple and feasible treatment would have an early opportunity to enter clinical research for the benefit of patients. (Source: Lu Xiaoxuan Huang Xin, China Science Journal)
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