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Immunological Responses after Exposure to Anthrax Spores in the U.S. Capitol, 2001

By Luciana L. Borio, M.D., January 18, 2007

Introduction

In a prospective, longitudinal, observational study published in the January 15 issue of the Journal of Infectious Diseases, Doolan and colleagues analyze the humoral and cell-mediated immune responses to B. anthracis among persons exposed and possibly exposed to spores in the U.S. Capitol complex in October 2001, during the anthrax bioterrorist attacks. [1]

In 2001, a letter containing anthrax spores was mailed to and opened in Senator Daschle’s office at the Hart Senate Office Building (HSOB). At the time, nasopharyngeal cultures (NPCs) were performed to help delineate an exposure zone. Individuals who were definitely or presumably exposed (groups 1 and 2) were offered antibiotics and anthrax vaccine adsorbed (AVA) immunization. AVA, which was chosen by 51/59 (86%) was administered on an abbreviated schedule at 0, 2, and 6 weeks (approximately 6, 8 and 12 weeks after exposure to spores). No one developed inhalational anthrax.

Doolan analyzed the clinical outcome and humoral/cellular immune responses after exposure to anthrax spores in this cohort from inside and outside the epidemiologically defined exposure zone. The cohort was stratified according to the presumed level of exposure, which was associated with NPC status and proximity to the letter at the time it was opened. Comparator groups were included. Results are summarized in the table below.

TABLE: Characteristics of the study and comparator groups:

GroupNumberNotes
Study Groups   
Within exposure zone
 
128Definite exposure & NPC+

 
231High risk of exposure & NPC−
Outer perimeter of exposure zone but elsewhere in the HSOB324Intermediate risk of exposure & NPC−
Outside exposure zone and HSOB, but in Capitol complex420Presumed no exposure, or low risk of exposure & NPC−
Comparator Groups   
Outside the Capitol complex
 
52History of confirmed anthrax disease
 
 
612No known exposure to B. anthracis
 
 
77Vaccinated controls (history of recent AVA)

Antibody and cell-mediated immune (CMI) responses to protective antigen (PA) and lethal factor (LF) were assayed in 124 people. The authors hypothesized that: 1) exposed individuals who remained asymptomatic while receiving antibiotics would mount PA- and LF-specific CMI responses, even in the absence of detectable anti-PA or anti-LF antibodies; 2) immune responses induced by AVA would be enhanced in individuals “primed” from spore exposure. Of note, the 20 people in group 4 who were outside the HSOB and presumed not be exposed to spores were the original negative control group in the study; however, unanticipated immune responses prompted enrollment of group 6.

Summary of Results

Nasopharyngeal culture: A spore exposure-dose response relationship was apparent; positive cultures occurred in 13/13 persons in the immediate vicinity of the letter, in 9/40 persons in adjacent areas, and in 6/7 first responders. Of note, repeat NPCs at 7 days were all negative. There were no positive NPCs in approximately 6,000 sampled people who were in the Capitol outside the HSOB (group 4).

Antibody and CMI response to exposure: In unimmunized persons, detected anti-PA total immunoglobulin was higher in groups 1 and 2 than in group 3. Anti-PA IgM and anti-LF antibodies were detected in groups 1 and 2 only.

In more than 94% of immunized persons, AVA induced anti-PA IgG and/or IgM antibodies. In addition, anti-LF antibodies were detected in immunized persons belonging to groups 1, 2, and 3, but not in group 7 (i.e. among people who were immunized and had no history of exposure to anthrax spores).

There was a dose relationship between presumed spore exposure and total PA or LF CMI responses. Albeit low, a CMI response was also detected in persons who were deemed to be at low or no risk of exposure because they were outside the HSOB (group 4). The authors state: “Unexpectedly, monocytic responses were detected in a higher proportion of subjects in groups 3 and 4 than in nonexposed control subjects in group 6.”

Conclusions

  • Prompt intervention with antibiotics and vaccination was highly effective against the disease even in those who were highly exposed.

  • More people were exposed to anthrax spores in the October 2001 attack on Daschle's office than previously known given that, unexpectedly, persons outside the HSOB, but in the Capitol complex, in areas predicted to be of minimal risk of exposure, had evidence of cell-mediated immune response.

  • NPC is an imperfect tool and a poor predictor of presence in an exposure zone – there were no detected differences in immune response profiles in groups 1 and 2, suggesting both groups had similar spore exposure.

  • Antibiotic prophylaxis was sufficient to abort infection, but did not inhibit an immune response. Low-level exposure generated cell mediated immune responses, whereas intermediate and high level exposure generated both humoral and cell-mediated immune responses. Contrast this finding with results of studies in rhesus monkeys which found that, when challenged with the inhalation of B. anthracis spores and treated with antibiotics, they do not develop anti-PA antibodies.[2]

  • Anthrax spores primed antibody and cellular immune responses in a dose-dependent manner, which enhanced the response to vaccination. This is an important finding as it suggests that in the event of a large scale bioterrorism attack employing anthrax spores, a post-exposure regimen of antibiotics plus an abbreviated vaccination schedule would be highly immunogenic and could allow for shortening the duration of antibiotic prophylaxis. This strategy has been successful in experiments with non-human primates.[3]

References

  1. Doolan DL, Freilich DA, Brice GT, et al. The U.S. Capitol Bioterrorism Anthrax Exposures: Clinical Epidemiological and Immunological Characteristics. J Infect Dis 2007;195:174-84.

  2. Friedlander AM, Welkos SL, Pitt ML, et al. Postexposure prophylaxis against experimental inhalation anthrax. J Infect Dis 1993;167:1239–43.

  3. Vietri NJ, Purcell BK, Lawler JV, et al. Short-course postexposure antibiotic prophylaxis combined with vaccination protects against experimental inhalational anthrax. Proc Natl Acad Sci U S A 2006;103:7813-6.

See also:

Hadler JL. Learning from the 2001 Anthrax Attacks: Immunological Characteristics. J Infect Dis 2007;195:163–4.