This was reported in Taiwan where the implementation of a nationwide hepatitis B vaccination program in 1984 was associated with a decline in the incidence of childhood hepatocellular carcinoma.

[14] The US Centers for Disease Control and Prevention (CDC) issued recommendations for vaccination against hepatitis B among patients with diabetes mellitus.

[33] An antibody level between 10 and 100 mIU/ml is considered a poor response, and these people should receive a single booster vaccination at this time, but do not need further retesting.

[33] People who fail to respond (anti-Hbs antibody level below 10 mIU/ml) should be tested to exclude current or past hepatitis B infection, and given a repeat course of three vaccinations, followed by further retesting 1–4 months after the second course.

Older literature assumed that immunity would wane with antibody titers and only effectively last five to seven years,[41][42] but immune-challenge studies show that even after 30 years, the immune system maintains the ability to produce an anamnestic response, i.e. to rapidly bump up antibody levels when the previously seen antigen is detected.

As a result, subsequent antibody testing and administration of booster doses is not required in successfully vaccinated immunocompetent individuals.

[45][46] UK guidelines suggest that people who respond to the vaccine and are at risk of occupational exposure, such as for healthcare workers, a single booster is recommended five years after initial immunization.

[13] Several studies have looked for an association between recombinant hepatitis B vaccine and multiple sclerosis (MS) in adults.

[54] The following is a list of countries by the percentage of infants receiving three doses of hepatitis B vaccine as published by the World Health Organization (WHO) in 2017.

[56] In 1963, the American physician/geneticist Baruch Blumberg, working at the Fox Chase Cancer Center, discovered what he called the "Australia Antigen" (HBsAg) in the serum of an Australian Aboriginal person.

[59] Blumberg had identified Australia antigen, the important first step, and later discovered the way to make the first hepatitis B vaccine.

The American microbiologist/vaccinologist Maurice Hilleman at Merck used three treatments (pepsin, urea and formaldehyde) of blood serum together with rigorous filtration to yield a product that could be used as a safe vaccine.

Hilleman hypothesized that he could make an HBV vaccine by injecting patients with hepatitis B surface protein.

Then, in the future, if the patient were infected with HBV, the immune system could promptly deploy protective antibodies, destroying the viruses before they could do any harm.

Hilleman devised a multistep process to purify this blood so that only the hepatitis B surface proteins remained.

[63] In 1981, William J. Rutter, Pablo DT Valenzuela and Edward Penhoet (UC Berkeley) co-founded the Chiron Corporation in Emeryville, California, which collaborated with Merck.

[63][64] The recombinant vaccine is based on a Hepatitis B surface antigen (HBsAg) gene inserted into yeast (Saccharomyces cerevisiae) cells which are free of any concerns associated with human blood products.

[17][65] This allows the yeast to produce only the noninfectious surface protein, without any danger of introducing actual viral DNA into the final product.

[65] In 2017, a two-dose HBV vaccine for adults, Heplisav-B gained U.S. Food and Drug Administration (FDA) approval.

[4] It uses recombinant HB surface antigen, similar to previous vaccines, but includes a novel CpG 1018 adjuvant, a 22-mer phosphorothioate-linked oligodeoxynucleotide.

[9] On 24 February 2022, the CHMP adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product PreHevbri, intended for the active immunization against hepatitis B virus infection (HBV).

[73] The applicant for this medicinal product is VBI Vaccines B.V.[73] PreHevbri was approved for medical use in the European Union in April 2022.

[77] Vaxelis is a vaccine against diphtheria, tetanus, pertussis, poliomyelitis, Haemophilus influenzae type B (Meningococcal Protein Conjugate), and hepatitis B.

[78][79] Fendrix (hepatitis B (rDNA) vaccine (adjuvanted, adsorbed)) was approved for medical use in the European Union in 2005.