Medical countermeasures include vaccines and therapeutics used to protect or
treat people from BW diseases. Developing new
countermeasures is very difficult. Therapeutic agent and vaccine development is
associated with extremely high costs. In 1993 drug companies spent on average
$359 million to develop a new drug for use in humans (46). Research and development
requires significant amounts of time and money to determine if a particular
therapeutic/vaccine has potential clinical utility. Once an appropriate agent is
found it must be tested in animals to see if it is toxic.
If the new drug/vaccine is not toxic in animals then it is tested for
toxicity, optimal dosages and efficacy in humans. Human testing involves three
different phases. Phase one can take several months and involves up to 100
patients to see if the drug is safe. Around 70 percent of the drugs get past
this phase. Phase two can take up to 2 years and involves several hundred
patients to ensure the drug is safe and will actually do what the researchers
think it should do. Only about 33
percent of the drugs that pass phase one get past phase two testing. Phase three
can involve up to several thousand patients and can take from 1-4 years to
complete. This phase of testing further ensures the safety of the drug/vaccine,
the appropriate dosage of the drug/vaccine, and determines if the drug/vaccine
is effective. Only around 25-30 percent of the drugs/vaccines that pass phase
two get past phase three (46).
During human testing of therapeutic agents researchers have to prove that
if a person becomes ill due to the microorganism that the drug it will help the
patient in eliminating the infection. If the infection is a rare then the study
will take much more time to complete to ensure the drug dosage is appropriate
and that the drug will actually help eliminate that infection. Developing
BW vaccines and treatments is unique in that most BW infections are very rare
(only 5 cases of anthrax from 1981 to 1999). It would take an enormous amount of
time to obtain the number of patients needed to test the drugís safety, dosage
and efficacy. To get enough data, in a timely fashion, on how effective a drug
is would require actually infecting people with the BW. There are very few
people willing to be exposed to a lethal BW in hopes of being rescued by a drug
or vaccine of unknown abilities (46).
Due to the lack of human studies there is currently insufficient data to show
that the current anthrax vaccine will protect people from inhalation anthrax.
Since it is believed that the most common and most deadly route of infection
following release of aerosolized anthrax would be by inhalation knowing if the
vaccine protects people infected in this way is important.
To aid in the new drug development effort the FDA in 2002 adopted an
animal test rule that will permit a demonstration of efficacy using animal
models. There are studies using rhesus monkeys that indicate the anthrax vaccine
protects against inhalation anthrax. This change in FDA regulations will speed
drug development however there are some inherent risks in using animal data
alone to determine drug safety, dosage and efficacy. Animals do not always
respond in the same way as humans do to vaccines or to therapeutics (30).
Vaccines are non-disease-causing preparations that induce the immune system
to mount a response. The immune response is so similar to the response needed
when a person is exposed to the disease-causing organism that they usually will
not develop disease. Even if an immunized person does become ill they are
usually much less likely to have serious disease following exposure to the
disease-causing organism. Vaccines can be composed of live attenuated
(non-pathogenic) organisms, killed (pathogenic) organisms or purified components
of the pathogen (protein or DNA). Vaccines are usually very specific. The
anthrax vaccine will only protect a person from developing anthrax following
exposure to the bacterium. It will not protect a person from smallpox or the
Vaccines do not provide immediate and complete protection. Even if a vaccine
can give complete protection with one injection it can take the body several
weeks to develop a good immune response. Many vaccines require multiple
injections over a couple months to give complete protection. Not all vaccines
give long-lasting protection and may require annual boosters. For a vaccine to
be maximally effective the last injection of the vaccine should be given well in
advance of exposure to the pathogen. Some vaccines have rare but severe
complications. The smallpox vaccine for instance is believed to cause 14 to 52
potentially life-threatening complications and 1-2 deaths per million
vaccinations (47). If the entire U.S. population were vaccinated to protect
against a smallpox attack some will probably die from the vaccine. Someone dying
following vaccination to protect them from a rare and possibly nonexistent BW
event is controversial.
Vaccines do not work the same in all people. Infants and the elderly tend not
to mount as good an immune response to vaccines. Live vaccines cannot be given
to everyone. If a live vaccine is given to someone with a compromised immune
system the organism in the vaccine could cause significant damage to the
patient. Pregnant women should not get live vaccines because the organism could
damage the fetus. So even if a great live vaccine with 100 percent efficacy is
developed it could not be given to every person in a country.
A lot of work does need to be done if the U.S. wants to develop safe and
effective vaccines for BW. The NIH believes that it can in the not too distant
future develop better replacement vaccines for anthrax and smallpox and provide
new vaccines for botulinum toxin, Ebola virus, Rift Valley fever virus and
tularemia (bacterial disease; Francisella tularensis) (30).
Therapeutic agents include drugs that are antimicrobial agents, immune modulators and antisera. There are a large number of good antimicrobial agents that work well against bacterial BW however there are very few antiviral agents that can be used to treat viral BW. Currently, there are no FDA approved treatments for viral BW. There is only one antiviral drug to treat smallpox (cidofovir) and its effectiveness is not proven. There are several antiviral drugs for treating Hepatitis B and C, herpes virus and HIV so there is hope that new antiviral drugs can be developed.
Immune modulators as the name implies modify the actions of the immune system. Some modulators stimulate the immune response while others suppress the immune response. Stimulation of the immune response has been found to be useful in helping a patient suppress certain viral infections. So far there is only one immune stimulator that is approved for treating viral infections (Herpes, viral warts, viral hepatitis) called Interferon. Interferon prevents viral replication and induces uninfected cells to produce antiviral proteins that prevent the virus from infecting it. There is another immune stimulant called interleukin-2 that helps the body respond to viral infections but it is currently only used to treat patients with renal cell carcinoma and melanoma. Some feel it might be useful in treating viral infections.
Antisera have also been used to treat botulinum toxin inhalation/ingestion. Antisera are antibodies to the toxin that prevent the toxin from poisoning the nervous system of the patient. There are polyclonal antisera that contain several different antibodies that react with different areas on the toxin and monoclonal antisera that contain only one type of antibody and it only reacts with one area on the toxin. Some researchers are also looking at monoclonal antibodies for their potential as immune modulators.
The NIHís strategic plan for therapeutics calls for developing antivirals effective against smallpox and the viral hemorrhagic fevers, antitoxins for use against anthrax and botulinum toxin, new types of antibiotics targeted against certain BW agents, and monoclonal antibodies to boost the immune systemís response to certain BW threat agents (30).
© 2005 Neal Chamberlain. All rights reserved.
Site Last Revised 5/6/05
Neal Chamberlain, PhD. A. T. Still University of Health Sciences/Kirksville College of Osteopathic Medicine.
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