The National Academies The Anthrax Vaccine Is It

The National Academies The Anthrax Vaccine: Is It Safe? Does It Work? 36 th National Immunization Conference Denver, Colorado

Background • Anthrax Vaccine Adsorbed (AVA) licensed in 1970 • Immunization requires 6 doses (SQ) over an 18 month period: 0, 2, 4 weeks, 6, 12, 18 months • In Dec, 1997, Do. D announced plans to immunize the total force of 2. 4 million service members in three phases over several years. The Anthrax Vaccine Immunization Program began March 1998. • Concerns were voiced about the vaccine. Congress required Do. D to sponsor an IOM study to evaluate the anthrax vaccine’s safety and efficacy. The first meeting took place October 2000.

The IOM Committee to Assess the Safety and Efficacy of the Anthrax Vaccine • • • Brian Strom (chair) William Barlow Dan Blazer Linda Cowan Kathryn Edwards • • Denise Faustman Emil Gotschlich Don Metzgar Hugh Tilson

Study Process • 8 deliberative meetings, with 4 public datagathering sessions • Committee heard from researchers and from service members and others with concerns about the vaccine • Reviewed published and unpublished information about AVA safety, efficacy and manufacturing

Study Information Sources Efficacy: reviewed the Brachman field trial, the observational data collected under the IND in the late sixties, and animal data Safety: reviewed case reports collected through VAERS, many ad hoc epidemiological studies, and analyses of data collected through the Defense Medical Surveillance System (DMSS) Manufacturing: reviewed documents from FDA inspections and Bio. Port responses and plans

Major Findings and Recommendations Efficacy: • …AVA as licensed is an effective vaccine for the protection of humans against anthrax including inhalational anthrax, caused by any known or plausible engineered strains of B. anthracis

• Additional passive and active protection studies in animals are needed to quantify protective levels of antibody • Additional research is needed on efficacy of AVA used post-exposure in combination with antibiotics

Major Findings and Recommendations Safety: Data from VAERS, DMSS and epidemiologic studies indicate: Local events, especially redness, swelling, or nodules at the injection site, are associated with receipt of AVA. These events are similar to the events observed following receipt of other adult vaccines, and are fairly common.

Major Findings and Recommendations Safety: Data from VAERS, DMSS and epidemiologic studies indicate: • Systemic events, such as fever, malaise, and myalgia are associated with receipt of AVA and are similar to the events observed following receipt of other adult vaccines. However, these systemic events are much less common than local adverse events.

Major Findings and Recommendations Safety: Data from VAERS, DMSS and epi studies indicate • Immediate-onset health effects can be severe enough in some individuals to result in brief functional impairment, but these effects are self-limited and result in no permanent health impairments. • There is no evidence that life-threatening or permanently disabling immediate-onset adverse events occur at higher rates in individuals who have received AVA than in the general population.

Major Findings and Recommendations Safety: • There are sex differences in local reactions following vaccination with AVA, as there after other vaccines. Women are more likely than men to experience and report injectionsite reactions. Factors accounting for these differences are not known. • The available data are limited but show no convincing evidence at this time that personnel who have received AVA have elevated risks of later-onset health events.

Major Findings and Recommendations Safety: • The currently licensed SQ route appears to be associated with higher incidence of immediateonset local effects than IM administration or a vaccination schedule with fewer doses. • Do. D should continue to support the CDC study of the reactogenicity and immunogenicity of an alternative route of AVA administration and a reduced number of vaccine doses.

Major Findings and Recommendations Safety: • Do. D should develop systems to enhance the capacity to monitor the occurrence of later-onset health conditions that might be associated with the receipt of any vaccine. Data reviewed by the committee do not suggest the need for special efforts of this sort for AVA. • Do. D’s DMSS is a promising population-based resource for monitoring the emergence of immediate- and lateronset heath concerns and for testing hypothesized associations between these concerns and military service exposures such as vaccines.

Major Findings and Recommendations Manufacture: • AVA will now be produced by a newly validated manufacturing process under strict controls, according to current FDA requirements. As a result the postrenovation product has greater assurance of consistency than that produced at the time of original licensure. • As with all vaccines, AVA lots produced postrenovation should be monitored for immunogenicity and stability, and individuals receiving these lots should be monitored for possible acute or chronic adverse events of immediate or later onset.

The Anthrax Vaccine: Is It Safe? Does It Work? is available free online at: http: //www. nap. edu/catalog/10310. html