Currently three anthrax vaccines are commercially available for human use. A live attenuated spore vaccine for humans was developed in the 1940s from a Sterne strain derivative and has been tested and used on a large scale in humans in the countries of the former Soviet Union (Shlyakhov and Rubinstein, 1994a). The British and U.S. anthrax vaccines were developed in the 1950s using filtrates of anthrax strains. Protective antigen, one of the three toxin proteins (discussed below), produced by the anthrax bacillus is the immunogenic component of both the U.S. and the U.K. vaccines. The British vaccine is an alum-precipitated cell-free filtrate of an attenuated Sterne strain culture and was licensed in 1979 (Pile et al., 1998).4 The U.S. vaccine is an aluminum hydroxide-adsorbed cell-free culture filtrate of an unencapsulated strain (Pile et al., 1998).
The anthrax vaccine was first produced on a large scale in the United States by Merck, Sharp, and Dohme in the 1950s for Fort Detrick (GAO, 1999c). Production was turned over to the Michigan Department of Public Health (MDPH) in the 1960s, and some changes were made in the manufacturing process; a different strain of anthrax was used in the MDPH vaccine, and the yield of protective antigen was increased (GAO, 1999c). In 1966, the Investigational New Drug (IND) application was submitted to the Division of Biologic Standards (DBS), formerly in the National Institutes of Health (NIH). Product licensure for Anthrax Vaccine Adsorbed was granted on November 10, 1970. The safety study of the anthrax vaccine submitted to the DBS contained information on the administration of approximately 16,000 doses. In 1985, an FDA advisory panel reviewing the status of bacterial vaccines and toxoids categorized the anthrax vaccine in Category 1 (safe, effective, and not misbranded) (FDA, 1985).
In December 1997, the Secretary of Defense announced that all U.S. military forces would receive anthrax vaccinations for protection against the threat of biological warfare. The Anthrax Vaccine Immunization Program (AVIP) began vaccinations in March 1998; the first personnel vaccinated were members of units deployed or scheduled to deploy to high-threat areas (Claypool, 1999).
It is estimated that 68,000 doses of the U.S. anthrax vaccine were distributed from 1974 to 1989; 268,000 doses in 1990; and 1.2 million doses from 1991 to July 1999 (Ellenberg, 1999). The exact number of people who received the vaccine is not known. The current dosing schedule is 0.5 ml administered subcutaneously at 0, 2, and 4 weeks and 6, 12, and 18 months, followed by yearly boosters. BioPort Corporation (previously Michigan Biologic Products Institute, formerly MDPH) manufactures the U.S. vaccine, approved for use in men and women age 18 to 65 years. The vaccine contains no more than 2.4 mg aluminum hydroxide per 0.5-ml dose as an adjuvant, formaldehyde as a stabilizer (final concentration ≤ 0.02 percent), and benzethonium chloride (0.0025 percent) as a stabilizer (BioPort, 1999; Friedlander et al., 1999).