These studies have employed anthraxin, an incompletely defined antigen used for skin testing. A positive delayed-type hypersensitivity reaction to anthraxin was associated with hyperemia of 64 mm2 and a twofold thickening of the skin.
Protective antigen-based vaccines. Protective antigen vaccines have had little use in veterinary practice but have been tested in laboratory animals either with or without adjuvant. The primary goal of these studies has been to determine the efficacy of injections of PA, with or without adjuvant, in protecting against infection with Bacillus anthracis. In addition, the studies have attempted to correlate the presence of antibodies with the degree of protection afforded by the vaccination.
Most studies in laboratory animals with the protective antigen vaccine have not mentioned adverse effects associated with vaccination. Many studies conducted in guinea pigs employed different vaccination regimens using culture filtrates of PA with and without alum adjuvant. Reports of these studies did not mention adverse effects (DeArmon et al., 1961; Klein et al., 1961; Puziss and Wright, 1963; Gulrajani et al., 1968; Little and Knudson, 1986; Ezzell and Abshire, 1988; Ivins, 1988; Ivins et al., 1986, 1989, 1990, 1993, 1994, 1995; McBride et al., 1998). In addition, reports of studies with similar vaccinations in mice and rabbits did not mention adverse events after vaccination (Wright et al., 1954; DeArmon et al., 1961; Puziss and Wright, 1963; Gulrajani et al., 1968; Ivins et al., 1990). The lack of data in these instances can indicate that no adverse effects occurred, that adverse events were not monitored, or that adverse events were not sufficiently severe to warrant termination of the experiment. The primary purpose of most of the studies was to evaluate the effectiveness of the vaccine against Bacillus anthracis infection. In general, most of the studies monitored animals for 1 to 2 months. A few studies extended to 1 or 2 years.
In a study by Wright and coworkers (1954), 25 rabbits received 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. Limited studies have also been conducted in nonhuman primates. A study in rhesus monkeys using the licensed anthrax vaccine revealed no remarkable local or systemic reactions (Ivins et al., 1998). Darlow and colleagues (1956) vaccinated 30 rhesus monkeys with the alum precipitate of the PA antigen and found no evidence of toxicity in the 10 animals that were monitored for 2 years. In this study, one control and one vaccinated animal developed a transitory illness and recovered within 3 days. The authors attributed the illness to a transitory infection, unrelated to the anthrax study. Three of the immunized animals monitored for the 2 years were reported to have died from other causes during the experimental period. Darlow also found that 50 ml of the vaccine preparation injected intravenously into rabbits resulted in no deaths and no apparent adverse effects. Wright and coworkers (1954) injected five monkeys with the PA antigen and did not mention any adverse effects. A booster injection given 3 months later did not cause significant local reactions or lesions observable on autopsy 3 weeks later.