Anthrax vaccine

Kathryn Dzintars, PharmD, BCPS
Pediatric Dosing Author: Lisa Hutchins, PharmD

VACCINE TYPE

  • Anthrax vaccine (AVA, BioThrax), killed vaccine made from the cell-free filtrate of the nonencapsulated, attenuated strain of B. anthracis culture that contains no live bacteria (note: a live attenuated vaccine was manufactured in the former USSR, but no longer available).

INDICATIONS

ACIP RECOMMENDATIONS

  • Routine vaccination with anthrax vaccine indications for persons engaged in:
  1. Work involving production quantities or concentrations of B. anthracis cultures.
  2. Activities with a high potential for anthrax aerosol production.
  • Routine anthrax vaccine NOT recommended:
    • Laboratory personnel using standard Biosafety Level 2 practices in the routine processing of clinical samples are not at increased risk for exposure to B. anthracis spores.
  • Veterinarians in the U.S. not recommended because of the low incidence of animal cases.
    • Vaccination may be considered in high-risk persons handling potentially infected animals in areas with a high incidence of anthrax cases.
  • For bioterrorism preparedness (e.g., first responders, federal responders, medical practitioners, and private citizens).
    • The Working Group on Civilian Biodefense does recommend vaccination of exposed persons following a biological attack in conjunction with abx administration for up to 60 days following exposure.
      • For immunocompetent adults aged 18 - 65 years, abx can be limited to 42 days if the AVA doses are administered on schedule and series completed.
      • For immunocompromised adults (cancer, HIV, receiving high-dose steroids for > 2 weeks, or radiation therapy) abx should be extended to 60 days.
      • All patients >65 years, all pregnant women and nursing mothers, and all children (< 17 years) should receive abx for 60 days.

OTHER INFORMATION

  • Post-exposure prophylaxis: AVA given as a sole agent was not effective in one primate study. AVA was effective if abx with activity against anthrax was given concurrently. The duration of post-exposure antimicrobial prophylaxis should be 60 days if used alone for PEP of unvaccinated exposed persons.
    • Approved for indication by FDA in November 2015.
  • Department of Defense has mandated some U.S. military active- and reserve-duty personnel receive pre-exposure (vaccine) prophylaxis as an adjunct to prolonged post-exposure antibiotic prophylaxis.
  • Pre-exposure vaccination of some persons deemed to be in high-risk groups should also be considered.
  • If anthrax vaccine supply is insufficient to vaccinate all exposed persons, dose-sparing options are available. Two doses of AVA with the second dose being given ≥ 2 weeks but ≤ 4 weeks after the initial dose. Antibiotics should be given concurrently with full protecting expected two weeks after the second dose is given.
  • Subcutaneous (SQ) administration is preferred over intramuscular (IM) because higher antibody concentrations are achieved 4 weeks post-vaccination. In a large scale emergency response, the IM route my be preferred if the SQ route of administration poses significant material, personnel or clinical challenges that would prohibit or delay vaccination.

FORMS

brand name

preparation

manufacturer

route

form

dosage^

cost*

BioThrax

Anthrax Vaccine Adsorbed

Bioport Corp, Lansing, Michigan.

SQ

Vial

10 doses/ vial

$900 per vial

*Prices represent cost per unit specified, are representative of "Average Wholesale Price" (AWP).
^Dosage is indicated in mg unless otherwise noted.

PATHOGEN DIRECTED PROTECTION

DOSE/ADMINISTRATION

Adult PRIMARY SERIES

  • Pre-exposure prophylaxis: 0.5 mL IM x 3 doses at 0, 6, and 12.
  • Post-exposure prophylaxis: 0.5 mL SQ x 3 doses, 0, 2 and 4 weeks after exposure.
    • Combine with antimicrobial therapy and possibly antibody administration (see anthrax prophylaxis modules for details).
    • Dose-sparing: 0.5 mL SQ x2 doses, 0 and ≥ 2 but ≤ 4 weeks after the initial dose.
  • Note: doses can be given IM or SQ, but IM recommended for pre-exposure and SQ for post-exposure prophylaxis.
  • There is no data on the use of this vaccine in people with HIV. It is assumed to be safe among people with HIV. Use general indications for vaccination. The immune response is likely best when the CD4 count is > 200 cells/mm3.

Adult BOOSTER

Revaccination:

  • 0.5 mL IM at 6 and 12 months after completion of the primary series.
  • Additional booster doses (0.5mL IM) are required and should be given every 3 years to maintain immunity.

Pediatric PRIMARY SERIES

  • Not approved or studied in children < 18 years old.
  • In conjunction with public health official guidance and on an event-by-event basis, an emergency use authorization (EUA) or investigational new drug (IND) application should be obtained to administer the regimen of 3 doses at 0, 2 and 4 weeks after exposure (along with antimicrobial prophylaxis) to pediatric patients between 6 weeks and 18 years of age.

ADVERSE DRUG REACTIONS

GENERAL

  • No long-term sequelae reported
  • Generally well tolerated

COMMON

  • Injection site nodule: most frequently reported local reaction and more common in women for unexplained reasons (60% vs 30% in men).
  • About 4% develop extensive erythema and swelling that may extend to the antecubital fossa --often misdiagnosed as bacterial cellulitis.

OCCASIONAL

  • Headache (0.4%)
  • Myalgia or arthralgia
  • Headache
  • Fatigue

RARE

  • Anaphylaxis

VACCINE/DRUG INTERACTIONS

  • No known drug interaction

CONTRAINDICATIONS

  • History of an anaphylactic reaction to the vaccine. Previous anthrax infection (re: more severe adverse events among recipients with a vaccine history of anthrax).

IMMUNE RESPONSE

The relationship between immunity and quantitative antibody levels has not been evaluated. The onset of protection: antibody titer increased 3-4x approximately 7d after the second dose (3-4 wks from the first dose). However, a clear minimum therapeutic antibody response has not been established but appears to be sufficient to prevent the development of disease once antibiotics were discontinued. An estimated 83% of human vaccinees develop a vaccine-induced immune response after two doses of the vaccine and >95% develop a four-fold rise in antibody titer after three doses.

CLINICAL EFFICACY

  • Effective in a placebo-controlled human trial against cutaneous anthrax. Primate models showed that antibiotic prevented inhalation anthrax, but was not protected from re-challenge.
  • However, all animals given vaccine PLUS antibiotics were protected with re-challenge[7].

OTHER INFORMATION

  • As post-exposure prophylaxis, the vaccine indicated only for risk of inhalation anthrax but prevents cutaneous anthrax as well.
    • AVA has been available since 1970.
  • Post-exposure prophylaxis with 60 days of antibiotics remains the cornerstone of management but since 2015, it now incorporates the AVA vaccine.
    • Only people who should not get the vaccine are those with a history of a serious reaction to a previous dose of AVA vaccine.
  • The risk for persons who come in contact in the workplace with imported animal hides, furs, bone meal, wool, animal hair, or bristles has been reduced by changes in industry standards and import restrictions.
    • Routine pre-exposure vaccination is recommended only for persons in this group for whom these standards and restrictions are insufficient to prevent exposure to anthrax spores.
  • Safety in Pregnancy: Category D. Earlier unpublished study of infants born to women in the U.S. military service worldwide in 1998 and 1999 suggest that the vaccine may be linked with an increase in the number of birth defects. However, a published study found no effect on pregnancy or adverse birth outcomes in a cohort involving 4092 women[6].
  • AV7909 is an investigational second-generation anthrax vaccine under development for PEP after inhalational anthrax exposure in conjunction with appropriate antimicrobials. It is intended to be added to the Strategic National Stockpile. The benefits of the investigational vaccine are that it only requires two doses given two weeks apart, conferring immunity 1 - 2 weeks sooner than the licensed, 3-dose vaccine, as well as improved compliance.
  • Potentially exposed persons should be observed for signs of febrile illness.

Basis for recommendation

  1. Bower WA, Schiffer J, Atmar RL, et al. Use of Anthrax Vaccine in the United States: Recommendations of the Advisory Committee on Immunization Practices, 2019. MMWR Recomm Rep. 2019;68(4):1-14.  [PMID:31834290]

    Comment: Updated recommendations from ACIP regarding the use of the Anthrax vaccine (AVA). Notable updates include (1) Administration of a booster dose to be given every 3 years to persons, not at high-risk, but who have previously completed the 3-dose series and initial 2-dose boosters to maintain protection, (2) recommendation of IM administration in place of SQ administration for ease of administration in an exposure setting, (3) recommendations on dose-sparing options to PEP regimens, and (4) adjustment to antibiotic durations for those patients 18 - 65 years of age who complete the vaccine series on schedule. Additionally, updated information on AV7909, an investigational anthrax vaccine is provided and may be recommended for potential emergency use.

  2. Hendricks KA, Wright ME, Shadomy SV, et al. Centers for disease control and prevention expert panel meetings on prevention and treatment of anthrax in adults. Emerg Infect Dis. 2014;20(2).  [PMID:24447897]

    Comment: An expert panel that has led to current recommendations updating antimicrobial postexposure prophylaxis and antimicrobial and antitoxin treatment options

  3. Wright JG, Quinn CP, Shadomy S, et al. Use of anthrax vaccine in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2009. MMWR Recomm Rep. 2010;59(RR-6):1-30.  [PMID:20651644]

    Comment: CDC/ACIP recommendations that update all prior.

  4. Vaccine Information Statement, Anthrax VIS. https://www.cdc.gov/vaccines/hcp/vis/vis-statements/anthrax.html (accessed 6/18/20)

    Comment: This statement handles both pre- and post-exposure prophylaxis. The vaccine has not been studied in ages < 18 years. If used in children, it will need to be done as part of an IND program.

References

  1. Hopkins RJ, Howard C, Hunter-Stitt E, et al. Phase 3 trial evaluating the immunogenicity and safety of a three-dose BioThrax® regimen for post-exposure prophylaxis in healthy adults. Vaccine. 2014;32(19):2217-24.  [PMID:24613523]

    Comment: This trial helped establish the pre-determined immunogenicity efficacy of the 3-dose SQ approach of AVA.

  2. Wiesen AR, Littell CT. Relationship between prepregnancy anthrax vaccination and pregnancy and birth outcomes among US Army women. JAMA. 2002;287(12):1556-60.  [PMID:11911758]

    Comment: A cohort study of 3136 pregnant women concluded that there were no maternal or fetal health effects from immunization.

  3. Friedlander AM, Welkos SL, Pitt ML, et al. Postexposure prophylaxis against experimental inhalation anthrax. J Infect Dis. 1993;167(5):1239-43.  [PMID:8486963]

    Comment: In this primate model, vaccination with our without concomitant antibiotic therapy proved protective.

  4. Clinical Framework and Medical Countermeasure Use Durin an Anthrax Mass-Casualty Incident. MMWR 2015;64(4). https://www.cdc.gov/mmwr/pdf/rr/rr6404.pdf (accessed 6/18/2020)

    Comment: The guideline emphasizes antimicrobial use for mass-causality, acutely ill patients. Vaccine not recommended here.

Anthrax vaccine is a sample topic from the Johns Hopkins ABX Guide.

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Last updated: July 3, 2020