Hepatitis B virus (HBV), a blood born infection, is a global health problem now targeted for elimination as a public health threat. In 2021, an estimated 296 million persons were chronically infected with HBV (HBsAg+) and 820,000 persons died of HBV related liver disease. Globally, HBV accounts for half of all hepatitis deaths and is leading cause of hepatocellular carcinoma. Of an estimated annual incidence of 1.5 million new chronic HBV infections, most were among young children. The risk for developing chronic HBV infection varies inversely with age at time of acute infection from 90% for HBV infected newborns, 30% of children infected between ages 1-4 years and < l 5% among persons of other ages. The high risk of chronic HBV infection increases the importance of Hepatitis B vaccination of children. First-generation, plasma-derived hepatitis B virus (HBV) vaccines were developed in the US and France in the late 1970s. In the mid-1980s, 2nd-generation recombinant DNA hepatitis B vaccines were constructed in yeasts transfected with HBV-DNA sequences. These vaccines are highly effective and safe. The vaccines are currently used for universal vaccination (UV) of newborns and adults in 179 countries worldwide. Third-generation HBV vaccines containing small (S), middle (Pre-S2, MHBs) and large (Pre-S1) HBV envelope proteins, also effective in non-responders to conventional vaccines, were developed in Israel, Germany, France and Korea in transfected mammalian cells. UV in neonates and children is leading to a significant reduction in the incidence of acute and chronic HBV infection as well as HCC worldwide. Globally, from 2000–2019, newborn and infant HepB vaccination prevented 22 million deaths averting one death for every 13 persons vaccinated. In 2018, global HBsAg prevalence among children < 5 years of age fell to < 1%, an interim 2020 target for HBV elimination. Recently two new highly immunogenic HBV vaccines were approved for use in adults by the US FDA and ACIP, namely the two dose Heplisav BTM a yeast derived vaccine containing the small S antigen, formulated with synthetic CpG and PreHevbrio™, the three antigen (Pre-S1/Pre-S2/S) mammalian cell derived HBV vaccine formulated with aluminum hydroxide, for prevention of HBV caused by all known subtypes of HBV in adults aged 18 years and older. The completion of the three-dose HepB vaccination protects against chronic HBV infection for at least 3–4 decades. The challenge now is to improve the vaccination coverage worldwide to achieve global goals for hepatitis B elimination.
Plotkin's Vaccines (Eighth Edition) 2023, Pages 389-432.e21,