Note from the Advisory Committee on Immunization Practices (ACIP) and the National Guideline Clearinghouse (NGC): These recommendations from the Advisory Committee on Immunization Practices (ACIP) update the previous recommendations for anthrax vaccine adsorbed (AVA) and reflect the status of anthrax vaccine supplies in the United States.
Substantial changes to these recommendations include the following: 1) reducing the number of doses required to complete the pre-event and preexposure primary series from 6 doses to 5 doses, 2) recommending intramuscular rather than subcutaneous AVA administration for preexposure use, 3) recommending AVA as a component of postexposure prophylaxis in pregnant women exposed to aerosolized Bacillus anthracis spores, 4) providing guidance regarding preexposure vaccination of emergency and other responder organizations under the direction of an occupational health program, and 5) recommending 60 days of antimicrobial prophylaxis in conjunction with 3 doses of AVA for optimal protection of previously unvaccinated persons after exposure to aerosolized B. anthracis spores.
Recommended Uses of Anthrax Vaccine
AVA may be used 1) via the licensed schedule to prevent infection by priming the immune system before exposure to Bacillus anthracis (pre-event or preexposure vaccination) and 2) after exposure to aerosolized B. anthracis spores under an Investigational New Drug (IND) or possibly under an Emergency Use Authorization (EUA [post-exposure prophylaxis (PEP) vaccination (see Tables below)]. Recommendations for the use of AVA differ for pre-event or preexposure vaccination and postexposure vaccination. For pre-event or preexposure vaccination, ACIP recommends 5 intramuscular (IM) doses administered at day 0, week 4, and months 6, 12, and 18, followed by annual boosters. To elicit the most substantial and rapid immune response possible among previously unvaccinated persons in a postexposure setting, PEP vaccination should be administered as a 3-dose subcutaneous (SC) series (at 0, 2, and 4 weeks) in conjunction with a 60-day course of appropriate antimicrobial agents.
Table. Recommended Preexposure and Postexposure Vaccination Schedules for Anthrax Vaccine Adsorbed
|Type of Prophylaxis
||5 doses (0 weeks, 4 weeks, 6 months, 12 months, and 18 months)
Annual booster to maintain immunity
||3 doses (0, 2, and 4 weeks)†,§
* For previously unvaccinated persons.
† In conjunction with 60-day antimicrobial postexposure prophylaxis.
§ Administered under an Investigational New Drug (IND) protocol or an Emergency Use Authorization (EUA)
Table. Recommendations for Use of Anthrax Vaccine Adsorbed, by Type of Population
||Postexposure Prophylaxis (PEP)†
|Special populations in the general public
|Children (aged <18 yrs)
||Determined on an event-by-event basis
|Populations at risk for occupational exposure
|Persons who handle animals or animal products
||Not routinely recommended§
|Persons who perform certain types of laboratory work
||Based on pre-event vaccination status
|Persons who work in postal facilities
||As recommended by the Department of Defense
||As recommended by the Department of Defense
|Persons involved in environmental investigations or remediation efforts
||Based on pre-event vaccination status
|Persons involved in emergency response activities**
||Not routinely recommended; may be offered on a voluntary basis under the direction of a comprehensive occupational health and safety program
* Five 0.5-mL doses administered intramuscularly at 0 weeks, 4 weeks, 6 months, 12 months, and 18 months; annual boosters are required to maintain immunity.
† Three 0.5-mL doses administered subcutaneously at 0, 2, and 4 weeks after exposure to aerosolized Bacillus anthracis spores for persons who have not completed the pre-event vaccination schedule.
§ Recommended only if handling potentially infected animals in research settings or in areas with a high incidence of enzootic anthrax or when standards and restrictions are insufficient to prevent exposure to B. anthracis spores.
¶ Laboratorians who work 1) with high concentrations or pure cultures of B. anthracis spores, 2) with environmental samples associated with anthrax investigations, or 3) in spore-contaminated areas or other settings with exposure to aerosolized B. anthracis spores. Laboratorians who do not work in these settings are not recommended for pre-event vaccine.
** Persons involved in emergency response activities might include persons who work in police departments, fire departments, hazardous material units, and the National Guard, as well as other government responders. These persons might perform site investigations, respond to suspicious substance reports (also known as white powder incidents), and perform other related activities, such as evacuation procedures or other activities critical to the maintenance of infrastructure.
Pre-event and Preexposure Vaccination
By priming the immune system before exposure to B. anthracis spores, pre-event and preexposure vaccination might provide more protection than antimicrobial agents alone to persons at risk for occupational exposure to B. anthracis, including protection for persons exposed to large inocula, protection if the public health infrastructure cannot ensure immediate availability or timely delivery of postevent antimicrobial agents, and potential benefits if bioengineered strains were released, limiting antimicrobial PEP effectiveness. The potential benefits from pre-event and preexposure vaccination should be weighed against the resource requirements to implement and maintain the vaccination schedule, as well as the potential adverse events associated with vaccination. Decisions for pre-event vaccination should be made based on a calculated risk assessment. In the absence of such an assessment, vaccination may be considered based on an estimated/presumed risk-benefit assessment. Depending on the occupational activities of the vaccine recipient, pre-event or preexposure vaccination might not eliminate the need for appropriate personal protective equipment.
Because the location and timing of a bioterrorism attack cannot be predicted, the risk-benefit profile for pre-event vaccination for the general public is low, and pre-event vaccination is not recommended. Preventing the morbidity and mortality associated with a deliberate release of B. anthracis depends on public vigilance, early detection and diagnosis, appropriate treatment, and rapid administration of PEP.
Pregnant and Breastfeeding Women
In a pre-event setting, in which the risk for exposure to aerosolized B. anthracis spores is presumably low, vaccination of pregnant women is not recommended and should be deferred until after pregnancy. Breastfeeding is neither a precaution nor a contraindication to vaccination, and vaccination does not need to be deferred in a pre-event setting if the occupation of the breastfeeding mother poses a risk for exposure to B. anthracis.
In a pre-event setting, in which the risk for exposure to aerosolized B. anthracis spores is presumably low, vaccination of children is not recommended.
Pre-event vaccination is not recommended for medical personnel. If exposed to aerosolized B. anthracis spores during a bioterrorism event, they should receive PEP in accordance with ACIP recommendations.
Populations at Risk for Occupational Exposure
Persons Handling Animals or Animal Products
Routine preexposure vaccination for persons who handle animals or animal products is recommended only for persons for whom previously discussed standards and restrictions are insufficient to prevent exposure to B. anthracis spores. Preexposure vaccination is not recommended for persons who routinely have contact with animal hide drums or animal hides; other preventive measures are available.
Routine vaccination of U.S. veterinarians and animal husbandry technicians is not recommended because of the low incidence of animal anthrax cases in the United States. However, vaccination might be recommended for veterinarians and other persons considered to be at high risk for anthrax exposure if they handle potentially infected animals in research settings or in areas with a high incidence of enzootic anthrax cases.
Preexposure vaccination is recommended for laboratorians at risk for repeated exposure to fully virulent B. anthracis spores, such as those who 1) work with high concentrations of spores with potential for aerosol production; 2) handle environmental samples that might contain powders and are associated with anthrax investigations; 3) routinely work with pure cultures of B. anthracis; 4) frequently work in spore-contaminated areas after a bioterrorism attack; or 5) work in other settings where repeated exposures to B. anthracis aerosols may occur.
Persons Working in Postal Processing Facilities
Because of biodetection systems in postal processing centers, contamination of mail with B. anthracis spores is likely to be detected rapidly, allowing postexposure therapy to be initiated immediately. Therefore, persons who work in these facilities are not recommended to receive pre-event vaccination.
Military personnel determined by Department of Defense (DoD) to have a calculable risk for exposure to aerosolized B. anthracis spores are recommended to receive preexposure vaccination. DoD has exclusionary criteria for employees, including an exclusion for pre-event vaccination of pregnant women.
Environmental Investigators and Remediation Workers
Vaccination is recommended for persons who, as part of their occupation, might repeatedly enter areas contaminated with B. anthracis spores.
Emergency and Other Responders
Emergency and other responders are not recommended to receive routine pre-event anthrax vaccination because of the lack of a calculable risk assessment. However, responder units engaged in response activities that might lead to exposure to aerosolized B. anthracis spores may offer their workers voluntary pre-event vaccination. The vaccination program should be carried out under the direction of a comprehensive occupational health and safety program.
Available data on AVA dosages suggest that increasing the interval between doses does not decrease the ultimate serologic response achieved or adversely affect the safety profile. Therefore, as with other vaccines, interruption of the vaccination schedule does not require restarting the entire series or the addition of extra doses.
PEP should be used for previously unvaccinated persons after exposure to aerosolized B. anthracis spores, whether the exposure is naturally occurring, occupationally related, or intentional. To elicit the most substantial and rapid immune response possible for previously unvaccinated persons in a postexposure setting, vaccination should be administered as recommended in conjunction with appropriate antimicrobial agents (Table 1 in the original guideline document and the "Recommended Preexposure and Postexposure Vaccination Schedules for Anthrax Vaccine Adsorbed" table above).
PEP After Inhalation Exposure
General Adult Population
ACIP recommends a postexposure regimen of 60 days of appropriate antimicrobial prophylaxis combined with 3 subcutaneous (SC) doses of AVA (administered at 0, 2, and 4 weeks postexposure) as the most effective protection against inhalation anthrax for previously unvaccinated persons aged ≥18 years who have been exposed to aerosolized B. anthracis spores.
After exposure to aerosolized B. anthracis spores, antimicrobial therapy should be initiated as soon as possible. Ideally, the first dose of vaccine should be administered within 10 days. Because AVA is not licensed for postexposure use, the vaccine will likely be made available either through an investigational new drug (IND) or an EUA during a public health emergency.
In general, the peak serologic response to anthrax vaccine occurs 10-14 days after the third dose. To ensure continued protection, persons for whom vaccination has been delayed should extend antimicrobial use to 14 days after the third dose, even though this practice might result in use of antimicrobials for >60 days. Antimicrobials should not be used for <60 days in previously unvaccinated persons who have been exposed to aerosolized B. anthracis spores.
In a postevent setting that poses a high risk for exposure to aerosolized B. anthracis spores, pregnancy is neither a precaution nor a contraindication to PEP. Pregnant women at risk for inhalation anthrax should receive AVA and 60 days of antimicrobial therapy as described.
In a postevent setting that poses a high risk for exposure to aerosolized B. anthracis spores, breastfeeding remains neither a precaution nor a contraindication to PEP. Breastfeeding women at risk for inhalation anthrax should receive AVA and 60 days of antimicrobial therapy as described.
The use of AVA in children is not contraindicated in a postevent setting that poses a high risk for exposure to aerosolized B. anthracis spores. During such an event, public health authorities will determine whether, under the existing IND protocol, to offer vaccine to children aged 0-17 years. Under this IND protocol, 3 doses of vaccine would be administered in conjunction with 60 days of appropriate antimicrobial therapy.
PEP After Repeated Occupational Exposures
The combination of pre-event vaccine and appropriate personal protective equipment (PPE) effectively protects fully vaccinated persons who work in occupations that might result in repeated exposure to aerosolized B. anthracis spores (see Table 4 in the original guideline document). Antimicrobial PEP is not needed for fully vaccinated workers who wear appropriate PPE while working in environments contaminated with B. anthracis spores unless the PPE is disrupted. However, fully vaccinated workers who prefer additional protection may consider antimicrobial PEP under the direction of their occupational health program.
A 30-day course of antimicrobial PEP is recommended for partially vaccinated workers (see Table 4 in the original guideline document), fully vaccinated workers who do not wear PPE, and fully vaccinated workers whose PPE has been disrupted; these workers should continue with their licensed vaccination regimen.
A 60-day course of antimicrobial PEP is recommended for previously unvaccinated workers. These workers also should begin receiving AVA as soon as possible using the PEP schedule of 3 SC doses.
PEP After Naturally Occurring Cutaneous or Gastrointestinal Exposure
Vaccination is not recommended after cutaneous or gastrointestinal exposures that pose no risk for inhalation exposure. When a naturally occurring cutaneous exposure occurs, appropriate medical and public health personnel should be notified, and affected persons should be monitored for development of a spot, pimple, or boil-like lesion, especially in the exposed areas. For persons who experience a naturally occurring gastrointestinal exposure, such those who eat meat from an undercooked carcass of an anthrax-infected animal, antimicrobial PEP for 7-14 days may be considered.
Contraindication and Precautions for Use of AVA
The following contraindication and precautions are relevant for both preexposure and postexposure settings.
Although anaphylaxis after anthrax vaccination is extremely rare and no anaphylaxis deaths associated with AVA have been reported, an anaphylactic reaction can be life-threatening. Therefore, AVA is contraindicated for persons who have experienced an anaphylactic reaction after a previous dose of AVA or any of the vaccine components.
- Latex allergy: Because the vaccine vial stopper contains dry, natural rubber, caution should be used when administering the vaccine to persons with a latex allergy. Epinephrine solution (1:1000) should be available for immediate use in the event that an anaphylactic reaction occurs.
- History of anthrax disease: A history of anthrax disease might increase the potential for severe local adverse reactions after AVA administration.
- Impaired immune response: Patients with an impaired immune response might not be adequately immunized after administration of AVA.
- Moderate or severe acute illness: In a standard preexposure vaccination program, vaccination of persons with moderate or severe acute illness should be postponed until after recovery. In a postevent setting, the risks of administering vaccine to a person who has been exposed to anthrax but has moderate or severe acute illness should be weighed against the benefits of vaccination. Vaccine may be administered to persons who have a mild illness with or without a low-grade fever.
Reporting Adverse Events
Adverse events that occur after administration of anthrax vaccine should be reported to Vaccine Adverse Event Reporting System (VAERS), regardless of whether the reporter considers the vaccine to be the cause of the event. Information about VAERS and how to report vaccine adverse events is available at http://vaers.hhs.gov . Adverse events that occur after administration of antimicrobial agents should be reported to the FDA MedWatch program at http://www.fda.gov/medwatch .