Learning from the 2001 Anthrax Attacks: Immunological Characteristics

opened in the Hart Senate Office Building (HSOB) in October 2001. The authors took advantage of this unfortunate but unique opportunity to conduct an observational study to determine whether high levels of inhalational exposure to anthrax spores resulted in clinical disease, as well as in humoral immune or cell-mediated immune (CMI) responses. This is one of the few studies of the immune response to high-level, naturally occurring anthrax exposure in humans, and it may be the first to describe CMI responses to this pathogen. The immune responses of persons with various levels of exposure, including an unexposed group and an unexposed but recently vaccinated group, are described, with data collected at 3 points in time: ~6, 8, and 12 weeks after exposure. The degree of exposure was determined by proximity in the HSOB and Capitol complex to the letter at the time when it was opened. The proximity measure of exposure correlated directly with the percentage in each group who had positive nasopharyngeal cultures within 24 h of the incident. In addition, the article describes the immune response to vaccination against anthrax among the subset of these groups who were vaccinated as part of the public health response. The key findings are that, although all highly exposed persons had immediately received antibiotics and there was no evidence that exposure resulted in clinical illness, sizeable percentages of persons highly exposed but not vaccinated had evidence of either humoral immune (40% to protective antigen [PA] and 14% to lethal factor [LF]) or CMI (80% to PA and ~60% to LF) responses. In addition, immune responses occurred mainly in persons with higher levels of exposure, and, for all measures of immunity, there was a notable doseresponse gradient. Vaccination of highly exposed persons also provoked detectable anti-LF antibodies in up to 40% of vaccinees. No one in the recently vaccinated, unexposed control group had detectable anti-LF antibodies; the anthrax vaccine used (anthrax vaccine adsorbed [AVA]) is geared toward the reliable production of PA antibodies only and not of LF [2]. Finally, a small percentage of persons minimally exposed (outside the HSOB but in the Capitol complex where positive environmental cultures were obtained) also had evidence of CMI responses. In addition to adding to the library of information about the immune response to anthrax spore exposure, this study may shed additional light on the pathogenesis of anthrax. The data obtained support the concept that exposure to high doses of potentially virulent anthrax spores in the setting of antibiotic prophylaxis to abort infection is sufficient to provoke an immune response. Furthermore, the variety of responses-particularly the humoral, cell-mediated, and postvaccination responses to LF-suggest that some people may have had spore germination with toxin secretion and exposure that was limited in extent and duration in the setting of antibiotics. The current anthrax vaccine used in the United States, AVA, consists principally of PA adsorbed onto aluminum hydroxide. As demonstrated in the study by Doolan et al., vaccination reliably produces responses to PA but only rarely to LE