Immune Responses toBacillus anthracisProtective Antigen in Patients with Bioterrorism‐Related Cutaneous or Inhalation Anthrax

Abstract

Anti-protective antigen (PA) immunoglobulin (Ig) G, toxin neutralization, and PA-specific IgG memory B cell responses were studied in patients with bioterrorism-related cutaneous or inhalation anthrax and in a patient with laboratory-acquired cutaneous anthrax. Responses were determined for >1 year after the onset of symptoms. Eleven days after the onset of symptoms (15 days after likely exposure), anti-PA IgG was detected in 16 of 17 patients with confirmed or suspected clinical anthrax who were tested. Anti-PA IgG remained detectable 8-16 months after the onset of symptoms in all 6 survivors of inhalation anthrax and in 7 of 11 survivors of cutaneous anthrax who were tested. Anti-PA IgG levels and serum toxin neutralizing activity were strongly associated (R2=0.83). PA-specific IgG memory B cells were detectable in all 6 survivors of inhalation anthrax but in only 2 of 7 patients with cutaneous anthrax who were tested. Anti-PA IgG is an important diagnostic marker of anthrax, a predictor of serum anti-toxin activity, and a marker of immunological memory against anthrax.

Patterns of antibody response in humans to the anthrax vaccine adsorbed (AVA) primary (six-dose) series☆

“…Binding of PA impedes toxin entry into cells, and is important in neutralizing B. anthracis LT in vivo and in vitro [20]. We and others have shown that there is strong correlation between IgG to PA and toxin-neutralizing activity after human infection with virulent anthrax, and vaccination with AVA [21,22].…”

“…Samples were retrieved from −70 • C storage that met preestablished criteria: (a) Vaccinations must have occurred within defined time intervals after receipt of the initial AVA injection (day 0 [dose #1], day 14 [range [11][12][13][14][15][16][17][18][19][20][21] ). (b) Pre-injection sera were defined as those taken on the day of each vaccine dose.…”

Serum IgG antibody response to the protective antigen (PA) of Bacillus anthracis induced by anthrax vaccine adsorbed (AVA) among U.S. military personnel

“…All serum samples were assayed for anti-PA IgG by ELISA as described [16] with the following modifications: PA antibodies were detected using mAb HP6043 anti-human IgG followed by alkaline phosphatase-labeled rat anti-mouse IgG [17].…”

Natural Exposure to Cutaneous Anthrax Gives Long-Lasting T Cell Immunity Encompassing Infection-Specific Epitopes

“…Studies of adaptive immunity to anthrax infection have focused overwhelmingly on serology, with only one study reporting T cell responses to PA (10)(11)(12)(13). Data from animal or human vaccination studies show that the induction of LT-neutralizing Ab by vaccines containing PA correlates with protection (14)(15)(16).…”