Research
The National Institute of Allergy and Infectious Diseases (NIAID) supports research on the diagnosis, prevention, and treatment of infections caused by microbes, including those that have the potential for use as biological weapons. The NIAID Biodefense Research Program includes both short- and long-term studies to design, develop, evaluate, and approve specific tools (diagnostics, treatments, and vaccines) needed to defend against possible bioterrorist-caused disease outbreaks.
In 2004, NIAID launched the Atopic Dermatitis and Vaccinia Network (ADVN), a nationwide research group that seeks to reduce the risk of EV, a severe and potentially deadly complication of smallpox immunization. EV occurs almost exclusively in people with a history of atopic dermatitis (AD)-a chronic, itchy skin condition commonly referred to as eczema. While uncommon, EV can develop when AD patients are given the smallpox vaccine or come into close personal contact with people who recently received the vaccine. If untreated, EV can kill between 1 and 6 percent of those affected. In children younger than 2 years of age, health experts estimate that EV can kill up to 30 percent.
Vaccine supply and strength
Expanding the U.S. smallpox vaccine supply is a high priority of the bioterrorism preparedness plan. In September 2001, the United States had only 15.4 million doses of smallpox vaccine available. Today there are more than 300 million doses. The increased supply is due in part to an NIAID-supported clinical trial that found that the smallpox vaccine Dryvax could successfully be diluted up to five times and retain its potency, effectively expanding the number of individuals it could protect from the contagious disease.
In addition, the government also funded a program, that is now completed, to produce more of a Dryvax-like vaccine using modern methods of production that meet current Food and Drug Administration (FDA) standards.
Because the currently available smallpox vaccine can have severe side-effects, however, NIAID also is pursuing the development of new, safer vaccines against smallpox. One of the most promising approaches is the modified vaccinia Ankara (MVA) vaccine. Unlike Dryvax, MVA cannot grow in human cells and therefore cannot form a lesion at the site of vaccination. Early clinical studies have shown that the vaccine was safe and effective in healthy volunteers. Phase II clinical studies are now underway to test the vaccine in both healthy individuals and those with compromised immune systems, such as those who are HIV positive.
Microbe biology
Variola and vaccinia belong to the Orthopoxvirus genus of poxviruses. Scientists who have sequenced the genes of several strains of variola and vaccinia have
- Found that genes for structural, membrane, and replication proteins appear to vary little among orthopoxviruses
- Identified some of the genes responsible for virus growth in human cells
NIAID will actively pursue further research in these areas.
Treatment
Research to evaluate new antiviral agents is ongoing. Early results from laboratory studies suggest that the drug cidofovir may fight against the smallpox virus. (In 1996, FDA approved the use of cidofovir to treat cytomegalovirus infections.) Scientists are doing studies with animals to better understand the drug's ability to treat smallpox.
Based on encouraging study results, NIAID has applied to FDA to use cidofovir as an experimental treatment for smallpox in the event of a bioterrorist-initiated re-emergence. In addition, NIAID has supported the development of a derivative of cidofovir that can be given orally instead of by intravenous injection and that may have fewer side-effects.
In addition to supporting cidofovir studies, NIAID has collaborated with the U.S. Department of Defense (DoD) to screen more than 1,100 compounds against smallpox and related viruses. NIAID-supported researchers are also evaluating experimental antiviral compounds in a number of mouse models of vaccinia and cowpox (another member of the orthopoxvirus family).
NIAID also supports mousepox virus and rabbitpox virus models. Compounds that are effective in these small-animal models are given priority for evaluation by DoD researchers in the monkeypox primate model.
In addition to collaborating with DoD scientists, NIAID is working with scientists at other federal agencies, such as CDC and the Department of Energy, to develop and test antiviral drugs against smallpox and determine whether existing antiviral compounds and those being developed are effective against variola virus.
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