The committee evaluated the primary peer-reviewed literature and did not draw conclusions from the secondary literature (e.g., reviews). Publications that were not peer reviewed had no evidentiary value for the committee, and they were not used as a basis for conclusions about the degree of association between an exposure and a health effect. The ability of the IOM to conduct the more comprehensive study of the anthrax vaccine requested by the DoD assumes that the significant body of work that has been conducted by the DoD on this subject will be released for publication in peer-reviewed scientific journals.
Currently there are two types of anthrax vaccine available for human use: a live attenuated spore vaccine that has been tested and used widely in the countries of the former Soviet Union (Shlyakhov and Rubinstein, 1994) and protective-antigen vaccines that were developed in the United States and the United Kingdom in the 1950s using filtrates of attenuated strains of the anthrax bacillus. Protective antigen, one of the three toxin proteins produced by the anthrax bacillus, is the protective component of the British and U.S. vaccines, which differ in their method of production and in the strains of the bacillus used (Ibrahim et al., 1999). The committee decided to base its conclusions solely on studies of the protective-antigen vaccines because the live attenuated spore vaccine differs substantially in terms of composition, reactogenicity, and potential residual virulence.
The U.S. anthrax vaccine, which was used in the Gulf War and is currently still in use, was granted product licensure on November 10, 1970. In 1985, a Food and Drug Administration (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). 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. 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 following sections provide a synthesis of the available peer-reviewed studies.
Few studies have explicitly looked for adverse health effects of the protective-antigen anthrax vaccine in animals. In a study by Wright and colleagues (1954), 25 rabbits were administered five 0.5-ml intracutaneous injections of anthrax vaccine on alternate days. The rabbits were sacrificed 23 days later. Complete autopsies including gross and microscopic examination of all organs revealed no adverse effects. In studies conducted in nonhuman primates, no remarkable local or systemic reactions were seen (Darlow et al., 1956; Ivins et al., 1998). Few meaningful conclusions regarding adverse effects in humans can be drawn from the animal studies of the vaccine; the primary goal of the majority of those studies has been to determine the vaccine’s efficacy.