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Research on Medical Tools to Combat Bioterrorism
The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), supports basic and clinical research on a variety of infectious and immunologic diseases. This research includes in-depth studies of infectious agents most likely to be intentionally released as a weapon of bioterrorism. Research focuses on development and evaluation of new and improved diagnostic tests, treatments, and preventive vaccines targeted to those agents.
As part of a larger effort coordinated by the Department of Health and Human Services, NIAID has made bioterrorism research a priority for several years. NIAID collaborates with the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration, the Department of Defense, and other government entities on multiple facets of bioterrorism research and policy activities.
Highlights of NIAID's current bioterrorism research projects are noted below. For more detailed information, see http://www.niaid.nih.gov/factsheets/btrsch.htm.
The Bioterrorism Threat. The threat of a bioterrorist attack against civilians differs from that against military personnel in several ways. Civilian groups generally are more vulnerable to such attacks because their age and health status range widely. Also, military personnel may have received mandatory vaccines to prevent infection with microbes that may be used as bioweapons. Moreover, bioterrorist attacks against civilian populations potentially can take more forms than those against the military.
Basic Research. Developing medical tools to counter bioterrorist threats requires thoroughly understanding these microbes and the human immune system's response to them. NIAID supports basic research to answer key questions, such as how these microbes multiply and become virulent; how antibiotic resistance develops; as well as what events are critical to initiating human infection or influencing the severity of disease.
Recently, NIAID has placed a major emphasis on generating information on the genetic make-up of potential bioterrorism agents. Coupled with knowledge in biochemistry, microbiology, and immunology, genomic information underpins many efforts to make rapid diagnostic tests, antimicrobial therapies, and new vaccines. NIAID has significantly invested in projects to sequence the full genomes of many pathogens, including the bacteria that cause anthrax, plague, Q fever, brucellosis, and glanders see (http://www.niaid.nih.gov/factsheets/seqmicrobes.htm). Other projects of note include the following:
- Smallpox. NIAID recently began supporting a collaborative project involving four academic centers, the CDC, the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), the Defense Advanced Research Projects Agency (DARPA), NIAID, and the American Type Culture Collection. Through this collaboration, databases have been created researchers can use to compare the sequences and functions of poxvirus genes. These searchable databases enable researchers to select targets for designing antiviral drugs and vaccines, and serve as repositories for information on well-documented poxvirus strains to aid in detection and diagnosis.
- Anthrax. With the Office of Naval Research (ONR), NIAID and the Department of Energy are funding a project to sequence the complete genome of the anthrax bacterium, Bacillus anthracis, and to determine the function of its genes. Information gained from this project will help reveal genes that control key biochemical processes or pathways that may be specific targets for treatment as well aid in the design of new diagnostic tests or vaccines. In addition, NIAID is funding basic research on genes that influence the virulence of and human immune response to the anthrax bacterium and its toxins, and on strategies to inactivate anthrax spores.
- Other agents. NIAID also supports basic research on the agents that cause plague, brucellosis, tularemia, and Ebola.
New Diagnostic Tools. An unusual upturn in cases of a disease, or a disease outbreak, likely will be the first sign of a bioterrorist attack. It is critically important to rapidly identify the microbe in the people who have become ill or in the environment where they work and live. NIAID supports research to develop ways to identify natural and bioengineered microbes, and to quickly establish a microbe's sensitivity to drug therapy.
- Smallpox. Through an agreement with NIAID, scientists at USAMRIID are currently developing new tests to rapidly diagnose infections caused by orthopoxviruses, particularly the smallpox virus, known as variola.
New Treatments. To provide medical care for the victims of a bioterrorist attack, NIAID supports the development and clinical testing of treatments for the diseases that result from such attacks. NIAID supports research to
Such studies often rely on knowledge about the microbe's genes, particularly those genes that enable it to multiply and cause disease.
- identify several drugs for each agent of bioterrorism
- develop medicines that are effective against multiple agents
- design new drugs for known drug-resistant microbes
- Smallpox. The need for smallpox treatments is particularly acute, as currently no specific treatments exist. NIAID recently funded four research projects aimed at developing novel drugs to treat infections with poxviruses, including variola, the smallpox virus, and vaccinia, the closely related laboratory virus that is the basis for the smallpox vaccine. Other NIAID-funded researchers are screening known antiviral compounds for activity against variola and vaccina as well as several other potential bioterrorism viruses. Several additional investigators are attempting to design and synthesize completely new antiviral compounds. NIAID has established agreements with USAMRIID to provide scale-up synthesis of promising experimental antiviral compounds for evaluation in animal models. NIAID and USAMRIID have funded screening of at least 500 compounds for potential antiviral activity against smallpox. Several promising leads will be further tested in laboratory or animal model tests, or in combination therapy studies.
Because the only available smallpox vaccine contains a weakened live vaccinia virus, it may occasionally cause complications. Such complications currently are treated with anti-vaccinia immune globulin - that is, pooled antibodies taken from individuals recently immunized with the smallpox vaccine. Because the United States discontinued routine smallpox vaccination programs in 1972, vaccinia immune globulin is in extremely short supply. NIAID-funded researchers are trying to develop replacements for vaccinia immune globulin based on laboratory-made antibodies.
As an additional safety measure, NIAID recently applied to the Food and Drug Administration for the use of the antiviral drug cidofovir as an experimental treatment for smallpox in the event of a bioterrorist-initiated re-emergence. Studies in monkeys and other animals, conducted through the agreement with USAMRIID, identified cidofovir as a promising drug active against various poxvirus infections.
- Other agents. NIAID also supports research on new and improved therapies directed toward anthrax and plague.
Preventive Vaccines. NIAID supports studies that use either traditional or novel technologies to develop new and improved vaccines to protect the public against. Efforts are under way to develop vaccines that are both safe and effective, as well as being easy to administer. These efforts require detailed knowledge of the human immune response to potential agents of bioterrorism so vaccines can be designed to protect people of varying ages and states of health.
- Smallpox. Historic data suggested the current smallpox vaccine could be diluted and still retain its ability to protect against infection. Last year, NIAID initiated a small clinical trial at Saint Louis University Health Sciences Center to establish the feasibility of "stretching" the currently available smallpox vaccine. Data from that small study suggested that a 1/10 or less dilution of the smallpox vaccine might work just as well as full-strength vaccine. A large follow-up, multicenter clinical trial, begun in the fall of 2001, has enrolled 680 people to determine if the smallpox vaccine might be diluted by 1/5 or 1/10 and still retain its potency. The results of this study will be known in early 2002. If results are favorable, the currently available stockpile of smallpox vaccine could supply 75 million doses or more.
NIAID plans to support clinical testing of new smallpox vaccines that may be safely used in immune-compromised individuals and other special populations. The Institute also is fostering research on alternative vaccine strategies, including DNA-based vaccines, with the goal of designing safer, more effective smallpox vaccines.
- Anthrax. NIAID has also initiated a collaborative effort with USAMRIID for anthrax vaccine development and testing. Studies are being conducted to help determine what immune responses protect against inhalation anthrax. In addition, studies under way are developing recombinant forms of a key piece of the anthrax bacterium, protective antigen, as experimental vaccines that can be tested in human clinical trials.
- Other agents. NIAID also supports research on vaccines against brucellosis, Q fever, and Ebola virus. A candidate Ebola vaccine made by researchers at NIAID's Vaccine Research Center has been shown to protect monkeys from Ebola virus infection.
NIAID is a component of the National Institutes of Health (NIH). NIAID supports basic and applied research to prevent, diagnose, and treat infectious and immune-mediated illnesses, including HIV/AIDS and other sexually transmitted diseases, illness from potential agents of bioterrorism, tuberculosis, malaria, autoimmune disorders, asthma and allergies.
Press releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov.
Office of Communications and Public Liaison
National Institute of Allergy and Infectious Diseases
National Institutes of Health
Bethesda, MD 20892
U.S. Department of Health and Human Services
December 7, 2001