Vaccination is the mainstay of hepatitis B virus (HBV) prevention and represents a core intervention in the World Health Organization’s (WHO) efforts to eliminate hepatitis B by 2030.[1] The first hepatitis B vaccine, which was plasma-derived, was first licensed in the United States in 1981 (Figure 1).[2] This vaccine contained purified plasma-derived hepatitis B surface antigen (HBsAg) and was safe and highly successful in preventing HBV infection.[2,3,4] Nevertheless, the first-generation plasma-derived HBV vaccine was tedious to manufacture, and the plasma-derived vaccine led to unsubstantiated concerns regarding the potential for bloodborne pathogen transmission and was eventually discontinued in 1992.[2]
By the mid-1980s, a second generation of hepatitis B vaccines became commercially available. These vaccines utilized recombinant DNA technology to express a nonglycosylated hepatitis B surface antigen in yeast cells, a process that was more cost-effective and scalable than the plasma-derived method.[2,3] Furthermore, yeast-derived vaccines eliminated any concern for vaccine-related bloodborne pathogen transmission.[2]
In the 1990s, mammalian cell-derived HBV vaccines became commercially available. These vaccines contained both the S antigen and either the pre-S2 or the pre-S2 and pre-S1 HBV antigens. Although studies suggested these vaccines were efficacious in conventional HBV vaccine nonresponders and overall more immunogenic than yeast-derived recombinant vaccines, manufacturing costs were higher, and they were not widely used.[5]
In 2017, the newest hepatitis B vaccine, HepB-CpG, was approved by the Federal Drug Administration (FDA). HepB-CpG, also known as Heplisav-B, contains a yeast-derived recombinant HBsAg as well as a novel cytidine-phosphate-guanosine oligodeoxynucleotide adjuvant that binds toll-like receptor 9 and stimulates a more robust immune response to HBsAg than the historical alum adjuvant.[6] HepB-CpG is recommended for use in adults ages 18 years of age and represents the fifth inactivated HBV vaccine recommended in the United States.[6]