The hepatitis vaccine was administered three times at the prescribed time, but when the five indicators of the hepatitis B virus (commonly known as two-to-one half) were retested several months later, the vaccine did not have an effect – the hepatitis B surface antibody was never produced. There are probably the following cases: (1) Inaccurate test method: antibodies have actually been produced, but the result is negative because the test method is inaccurate. In this case, the most sensitive method, such as enzyme-linked immunoassay or radioimmunoassay, should be used to retest. Because there are places where the detection method is not advanced or sensitive and yield false-negative results. (2) Weak immune response: The immune response of the body to the vaccine is so weak that only a trace of antibodies is produced, so much so that no trace of surface antibodies can be found even with advanced detection methods. In this case, the dose of hepatitis B vaccine can be increased (10 micrograms each time) and injected once a month for a total of 3 times. At the same time, the combination of hepatitis B vaccination with other immune-stimulating drugs, such as porcine polysaccharide and BCG vaccine, is thought to improve the immune effect. (3) Occult infection has occurred: If surface antibodies are not produced even after vaccination for the required time, PCR (in vitro nucleic acid amplification technique) can be applied to detect hepatitis B virus nucleic acid (HBV-DNA) in the serum of the vaccinated person. Because, there are a few patients who have actually been infected with hepatitis B virus, but the amount of their hepatitis B surface antigen (HBsAg) is so small that it cannot be detected by existing detection methods, or the hepatitis B virus has mutated and does not react with common reagents, and there may be other reasons as well. Although these patients have been infected with hepatitis B virus, they do not produce an immune response and the organism is in a state of immune tolerance, and in such cases, surface antibodies will not be produced when the hepatitis B vaccine is administered again. Alternatively, other hepatitis B virus markers such as core antibody (anti-HBc), e antibody and e antigen can be tested for positivity. If it is positive, it means that the virus is infected, and in this case, further injection of hepatitis B vaccine may not produce anti-HBs either. (4) Family history of hepatitis B: or people who have frequent contact with hepatitis B patients should pay special attention to the effect of hepatitis B vaccination. The chance of hepatitis B family members being infected with hepatitis B virus is extremely high, and there are some members who are infected with hepatitis B virus and appear to be insidious. Children born to people with hepatitis B should always be given the hepatitis B vaccine in a timely manner after birth, as this will block most of the transmission of the hepatitis B virus. However, even with timely hepatitis B vaccination, there are still very few newborns who fail immunization, which may be related to maternal intrauterine infection with hepatitis B virus during pregnancy and genetic factors. Parents need not make a fuss about this, nor should they use drugs indiscriminately; it is vital to review regularly and pay attention to changes in liver function. (5) Immunocompromised and immunodeficient people: people with similar conditions do not easily produce antibodies, such as those with end-stage renal disease, after organ transplantation, and AIDS infection. (6) Mutation of hepatitis B virus: mutated virus with new biological characteristics can make the hepatitis B vaccine ineffective. In addition, some people infected with hepatitis B virus have different subtypes of hepatitis B virus surface antigen. There are various subtypes, and the hepatitis B vaccine is designed for the main virus subtypes, so there are inevitably subtypes that cannot be taken into account, and if they are rare virus subtypes, the hepatitis B vaccine will not have a protective effect. (7) In addition, even if some people receive the full hepatitis B vaccine, 5% to 10% of the vaccinees do not produce hepatitis B antibodies or only produce low titers of antibodies, and these non-responders or low responders should receive the hepatitis B vaccine several times until antibodies are produced. In conclusion, if the hepatitis B vaccine does not produce antibodies, an additional course of vaccination can be given; if antibodies are not yet produced, attention should be paid to exclude whether the child is an insidious or low-level hepatitis B virus infected person, and whether there is a mutation of the hepatitis B virus.