What is therapeutic hepatitis B vaccine? Hepatitis B virus (HBV) carriers and chronic hepatitis B are two clinical manifestations of chronic HBV infection. 2002 epidemiological survey shows that there are about 120 million chronic HBV carriers and about 30 million cases of chronic hepatitis B in China, and some of these chronic HBV infected patients can progress to cirrhosis or hepatocellular carcinoma. HBV infection has become a serious public health problem and a serious threat to human health. However, in terms of treatment, HBV carriers and chronic hepatitis B share common and intractable problems: (1) HBV exists in the liver for a long time and replicates to varying degrees, and it is difficult to eradicate the virus with current antiviral drugs; (2) the vast majority of patients are immune tolerant to HBV and its antigens, which makes HBV in the liver immune to killing, thus facilitating the persistence and replication of the virus in the liver. Therefore, in order to completely remove HBV from infected patients, we must break the immune tolerance to HBV and rebuild the body’s immunity to HBV. For this reason, the hope of treating chronic HBV infection is placed on therapeutic hepatitis B vaccine. So, what is a therapeutic hepatitis B vaccine? Jianhua Yi, Department of Infection, Wuhan Union Hospital Therapeutic hepatitis B vaccine is a new type of vaccine that can break immune tolerance and rebuild or enhance immune response in chronic HBV-infected patients, and achieve the purpose of clearing hepatitis B virus from liver cells by stimulating the production of neutralizing antibodies and cellular immune response based on cytotoxic T lymphocyte response in HBV-infected patients. The traditional hepatitis B vaccine is only used for people who are not infected with HBV and generally has only a preventive effect. The therapeutic hepatitis B vaccine, on the other hand, is used for people who are already infected with HBV, and its strength is to “teach” the body’s immune system to correctly identify the “enemy”, break the body’s immune tolerance, produce autoantibodies and specific immune responses, and kill or even eliminate the hepatitis B virus from the body. Hepatitis B virus in the body. The therapeutic hepatitis B vaccine currently under research The once-hoped-for “ultimate weapon” therapeutic hepatitis B vaccine has not been able to come out of the laboratory for 20 years, and no therapeutic hepatitis B vaccine has been officially marketed internationally or domestically. The hepatitis B antigen-antibody complex vaccine “Bq” developed by Fudan University and Beijing Institute of Biological Products is one of them. The vaccine is a protein vaccine that combines HBV surface antigen and high-valent hepatitis B immunoglobulin in a certain ratio to form an antigen-antibody complex for the treatment of chronic hepatitis B. The project is led by academician Wen Yumei of Fudan University and has been the most systematic and in-depth research in China for nearly 20 years, and is currently undergoing phase III clinical trials. 2. The therapeutic hepatitis B vaccine jointly developed by the Third Military Medical University and Chongqing Brewery Company is a peptide biologic product based on the principle of molecular epitope design, which is synthesized by imitating certain peptide chains of hepatitis B antigen to induce cells to produce antibodies, and is a peptide vaccine. The project is led by Professor Wu Yuzhang of the Third Military Medical University, and is also currently undergoing phase II clinical trials. In addition, the therapeutic hepatitis B vaccine researched by Professor Zhang Yijun of Guangzhou Air Force Hospital in cooperation with Shenzhen Kangtai Biologicals and the therapeutic DNA vaccine researched by a research collaborative group led by Chen Guangming have been approved for Phase II clinical study. The above-mentioned therapeutic vaccines that have entered clinical trials are based on two different research lines: Fudan University researches an immune complex composed of hepatitis B surface antigen and high-valent hepatitis B immunoglobulin, a vaccine that activates the human immune system to clear the virus; Third Military Medical University uses a mock antigen as the immunogen to overcome immune tolerance and synthesize a peptide vaccine molecule that can effectively activate T cells and produce immune peptide vaccine molecules – the common principle is to activate the dormant immune system to fight the hepatitis B virus. Will a therapeutic hepatitis B vaccine be available soon? There are media reports that a domestic therapeutic hepatitis B vaccine will soon complete Phase III clinical trials and receive a new drug certificate by August 2008. There are even media reports that the research on therapeutic hepatitis B vaccine has made a “major breakthrough” and will be available soon, so much so that HBV-infected patients think that they can solve all the problems of chronic HBV infection once and for all through the injection of therapeutic hepatitis B vaccine. This is actually misleading to the majority of HBV-infected people, and I am afraid that the market interest is still behind it. According to incomplete statistics, the treatment cost of HBV infection-related diseases in China is about 900 billion yuan/year, and in the face of such huge market interests, investors are sure to hope to make profits from it. Therefore, we cannot rule out the possibility of market speculation by investors or listed companies. It should be said that the research of therapeutic hepatitis B vaccine is a direction, if the combination of antiviral drugs and therapeutic vaccine is applied, it is possible to clear the hepatitis B virus in the body. However, none of them have been successfully marketed so far, and none of them have been able to come up with final clinical trial results. In fact, some international pharmaceutical giants such as Merck and GlaxoSmithKline have invested heavily in the research of therapeutic hepatitis B vaccines, but eventually they all backed out because they did not see any hope of success. Does entering clinical trials necessarily mean success in the end? Obviously not. Even if a Phase III clinical trial is completed, it does not mean that the therapeutic hepatitis B vaccine is a success, and there is no shortage of cases in the history of drug research where new drugs have been eliminated in Phase III clinical trials. The efficacy and safety of the therapeutic vaccine, the existence of serious life-threatening side effects, the dose of the vaccine, and the indications for treatment, i.e., which HBV-infected patients are suitable for treatment, are not yet known; in addition, individual differences in HBV-infected patients, hepatitis B virus variation, the complex immune response of the body, and the relationship between the therapeutic vaccine and existing antiviral therapy In addition, individual differences in HBV-infected patients, hepatitis B virus variation, the complex immune response of the body, and the relationship between therapeutic vaccines and existing antiviral therapy may affect the efficacy of therapeutic vaccines. Even academician Wen Yumei is very cautious about the evaluation of his research. We know that current antiviral therapies do not completely eradicate HBV mainly because they do not work on the covalently closed circular DNA, the replication template of HBV in the nucleus of hepatocytes, and therapeutic hepatitis B vaccines also do not work on this. Therefore, it is too early to talk about its efficacy. Even if the Phase III clinical trial is successfully completed, the therapeutic vaccine will have to go through a series of steps such as registration filing and passing the State Food and Drug Administration’s new drug review before it can be qualified for marketing. Therefore, it is difficult to precisely estimate the time to market. What can we do now? At present, for the majority of chronic hepatitis B patients, the correct choice should be to develop a standardized individualized antiviral treatment plan under the guidance of a specialist and adhere to antiviral therapy to maximize the suppression of viral replication and interrupt the occurrence of cirrhosis or hepatocellular carcinoma. Do not delay treatment by blindly waiting for a therapeutic hepatitis B vaccine to become available. Even if a therapeutic hepatitis B vaccine is successfully developed and marketed, it cannot replace antiviral drugs, and one vaccine should not be expected to solve all the problems of HBV infection. It is better to combine it with antiviral drugs to achieve long-term suppression or clearance of hepatitis B virus.