vaccine in the United States (Beasley et al., 1983; McLean et al., 1983; Szmuness et al., 1980, 1982; Wong et al., 1984). The vaccines were used very widely, especially in Asia.
Recombinant vaccines are produced by Saccharomyces cerevisiae (common baker's yeast), into which a plasmid containing the gene for HBsAg has been inserted. These were developed and licensed in the 1980s (Emini et al., 1986; Stephenne, 1990). Purified HBsAg is obtained by lysing the yeast cells and separating HBsAg from the yeast components by biochemical and biophysical techniques. These vaccines contain more than 95 percent HBsAg protein. Yeast-derived protein constitutes no more than 5 percent of the final product. Hepatitis B vaccines are packaged to contain 10-40 µg of HBsAg protein per ml and are absorbed with aluminum hydroxide (0.5 mg/ml). Thimerosal (1:20,000 concentration) is added as a preservative. In 1986, the first recombinant hepatitis B vaccine was licensed in the United States. Two recombinant vaccines, both produced in yeasts, are currently licensed in the United States (by Merck Sharp & Dohme and SmithKline Biologicals). These recombinant vaccines are also used in many countries worldwide. An additional recombinant vaccine that is produced in mammalian cells (Pasteur-Merieux) is available in some countries in Europe (Hadler and Margolis, 1992). Recombinant vaccines are also produced in Japan and may become widely available in the future. Additional second-generation recombinant vaccines are currently under development.
Plasma-derived vaccine is no longer being produced in the United States, although it is being produced inexpensively in other countries and has become the predominant form of vaccine in much of Asia, where it is being used in national programs to attempt to interrupt maternal-neonatal transmission. In 1991, hepatitis B vaccine was recommended by both the Centers for Disease Control and the American Academy of Pediatrics for universal administration to infants.
The Advisory Committee on Immunization Practices and the American Academy of Pediatrics recommend that hepatitis B vaccine be given at birth and then again at ages 1 to 2 months and 6 to 18 months. The Advisory Committee on Immunization Practices also recommends an alternative to that schedule of administration, that is, at ages 1 to 2 months, 4 months, and 6 to 18 months.
The antibodies produced after infection with hepatitis B virus or after administration of plasma-derived vaccine or recombinant vaccine are alike in terms of their ability to elicit protective determinants that are active against all subtypes of the virus (Hauser et al., 1987). In the United States,