licensure of AVA (Brachman et al., 1962). Although that study had too few cases to evaluate the vaccine’s efficacy for the prevention of inhalational disease, the five inhalational cases observed during the trial occurred only among nonvaccinated or placebo recipients. Data from CDC on cases reported between 1962 and 1974 also indicated that the vaccine offered protection against the cutaneous form of the disease (FDA, 1985). Further-more, laboratory experiments indicate that AVA provides effective protection against inhalational challenge in rabbits and macaques, the animal models in which the disease is most reflective of the disease in humans (Fellows et al., 2001; Ivins et al., 1996, 1998; Pitt et al., 2001). Because PA is critical to the virulence of B. anthracis and because PA’s structure is so highly conserved, it appears likely that changing its structure would alter and thus eliminate its toxic action. Data from studies with animals suggest that AVA will offer protection against strains with PA-based toxicity. Finally, the available data indicate that immunity to anthrax is associated with the presence of antibodies to PA, such as those stimulated by the anthrax vaccine.

As with any pharmaceutical product or medical procedure, the use of vaccines carries a risk of adverse health effects that must be weighed against the expected health benefit. Expectations for the safety³ of vaccines are especially high because, in contrast to therapeutic agents, which are given when a disease is known to be present (or at least suspected), vaccines are usually given to people who are healthy to protect them against a disease that they may not be exposed to in the future.

The committee evaluated case reports and epidemiologic studies providing information about the safety of the anthrax vaccine. Case reports can help to generate hypotheses about possible associations but are rarely sufficient by themselves to confirm such associations. Formal epidemiologic studies are usually needed to determine whether those adverse events iden-

Front Matter (R1-R22)

Executive Summary (1-32)

1 Introduction (33-39)

2 Background (40-55)

3 Anthrax Vaccine Efficacy (56-82)

4 Safety: Introduction (83-101)

5 Safety: Case Reports (102-117)

6 Safety: Epidemiologic Studies (118-179)

7 Anthrax Vaccine Manufacture (180-197)

8 Future Needs (198-210)

Appendix A Statement of Task (211-213)

Appendix B Biographical Sketches (214-217)

Appendix C Information-Gathering Meeting Agendas (218-226)

Appendix D Anthrax Vaccine Adsorbed Package Inserts (227-238)

Appendix E Vaccine Adverse Event Reporting System (VAERS) Form (239-242)

Appendix F Anthrax Vaccine Expert Committee (AVEC) Case Assessment Form (243-244)

Appendix G DMSS Analyses Requested by the IOM Committee to Assess the Safety and Efficacy of the Anthrax Vaccine (245-252)

Appendix H An Assessment of the Safety of the Anthrax Vaccine: A Letter Report (253-266)