Immunity to Anthrax

Considerable variation in genetic susceptibility to anthrax exists among animal species. Resistant animals fall into two groups: (1) resistant to establishment of anthrax but sensitive to the toxin and (2) resistant to the toxin but susceptible to establishment of disease. This is illustrated in the table below. Neither the source of the inoculum (spores or vegetative cells or a mixture) nor the route of inoculation (subcutaneous, gastrointestinal, or inhalational) is stated. The infectious dose of anthrax is expected to vary widely based on these parameters, as well.

Table 2. The infectious dose of B. anthracis  and the lethal dose of toxin varies greatly within animal species. The data do not specify the route of infection or whether spores or vegetative cells were used in the inoculum.

Animal model	Infectious dose	Toxic dose causing death	Bacteria per ml blood at time death
Mouse	5 cells	1000 units/kg	107
Monkey	3000 cells	2500 unit/kg	107
Rat	106 cells	15 units/kg	105

Animals surviving naturally-acquired anthrax are immune to reinfection. Second attacks are extremely rare. Permanent immunity to anthrax seems to require antibodies to both the toxin and the capsular polypeptide, but the relative importance of the two kinds of antibodies appears to vary widely in different animals.

Vaccines composed of killed bacilli and/or capsular antigens produce no significant immunity. A nonencapsulated toxigenic strain has been used effectively in livestock. The Sterne Strain of Bacillus anthracis produces sublethal amounts of the toxin that induces formation of protective antibody.

The anthrax vaccine for humans, which is used in the U.S., is a preparation of the protective antigen recovered from the culture filtrate of an avirulent, nonencapsulated strain of Bacillus anthracis that produces PA during active growth. Anthrax immunization consists of three subcutaneous injections given two weeks apart followed by three additional subcutaneous injections given at 6, 12, and 18 months. Annual booster injections of the vaccine are required to maintain a protective level of immunity.

The vaccine is indicated for individuals who come in contact in the workplace with imported animal hides, furs, bone, meat, wool, animal hair (especially goat hair) and bristles; and for individuals engaged in diagnostic or investigational activities which may bring them into contact with anthrax spores. Otherwise, it has been indicated for the military during the current era of biological warfare.

The vaccine should only be administered to healthy individuals from 18 to 65 years of age, since investigations to date have been conducted exclusively in that population. It is not known whether the anthrax vaccine can cause fetal harm, and pregnant women should not be vaccinated.

A new type of passive vaccine to anthrax is currently on the horizon. This was recently announced by R.G. Crystal and colleagues from the Medical College of Cornell University, in the February, 2005 issue of the journal, Molecular Therapy. They demonstrated that mice vaccinated with a human adenovirus expressing a single-chain antibody directed against protective antigen (PA) became immune to anthrax within 24 hours of vaccination. This is much quicker than is possible with existing anthrax vaccines, which are a relatively crude preparation of PA.

Currently available anthrax vaccines have limited use in a bioterrorism attack because they are active vaccines in which multiple doses are required over several months to elicit protective immunity against anthrax. Passive vaccines, on the other hand, introduce fully formed antibodies directly to the body and immunity is achieved much sooner.

In mice receiving the adenovirus-based anti-PA vaccine, PA-specific serum antibodies were detectable within 24 hours. These antibodies had neutralizing activity that protected mice from an intravenous lethal toxin challenge administered 1-14 days post vaccination.

Crystal, et al envision a possible scenario wherein both the passive and active vaccine might be given. Passive vaccines lose their effectiveness fairly rapidly over time, whereas active vaccines do not. The passive vaccine could provide protection that would last a couple of weeks, but that would provide a safety margin for development of more active, long-term immunity stimulated by the active vaccine.

Passive immunotherapy with such adenovirus-based vectors expressing anti-PA antibody, either alone or in combination with antibiotics, may be a rapid, convenient, and highly effective strategy to protect against or treat anthrax in a bioterrorism attack.

Also, in cases of anthrax, coadministration of the passive vaccine with antibiotics may maximize the utility of antibiotic therapy. Coadministration would counter the effects of lethal toxin, and likely prolong the time frame for effective antibiotic treatment and/or reduce the amount of antibiotic therapy required.

Treatment of Anthrax

Antibiotics should be given to unvaccinated individuals exposed to inhalation anthrax. Penicillin, tetracyclines and fluoroquinolones are effective if administered before the onset of lymphatic spread or septicemia, estimated to be about 24 hours. Antibiotic treatment is also known to lessen the severity of disease in individuals who acquire anthrax through the skin. Inhalation anthrax was formerly thought to be nearly 100% fatal despite antibiotic treatment, particularly if treatment is started after symptoms appear. A recent Army study resulted in successful treatment of monkeys with antibiotic therapy after being exposed to anthrax spores. The antibiotic therapy was begun one day after exposure.