Volunteer for NIAID-funded clinical studies related to smallpox on ClinicalTrials.gov.
NIAID supports basic, preclinical, and clinical research needed to advance product development for biodefense and emerging infectious diseases. Product development goals in this arena have shifted from a “one bug-one drug” approach to a more flexible strategy that is applicable to a broad spectrum of infectious diseases. Specifically, this broad-spectrum approach is being used to develop products effective against a variety of pathogens and toxins; find technologies that can be widely applied to improve multiple classes of products; and establish platforms that can reduce the time and cost of creating new products. This is evident in both the treatment and vaccine research NIAID has supported for smallpox, outlined below.
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.
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 is the modified vaccinia Ankara (MVA) vaccine. NIAID has supported the development of MVA from preclinical evaluation through Phase II clinical trials. More than 2,000 healthy volunteers, more than 250 HIV-positive volunteers and more than 250 volunteers positive for atopic dermatitis or with a history of atopic dermatitis have been vaccinated with the MVA vaccine. These trials have evaluated factors such as safety, immunogenicity, duration of protection, and route of vaccination. MVA has been transitioned to the Biomedical Advanced Research and Development Authority (BARDA) for delivery to the Strategic National Stockpile (SNS). MVA currently is also in development as a platform for both cancer vaccines (prostate and breast) and other infectious agents (HIV and respiratory syncytial virus).
Although smallpox vaccines have been developed and procured for the SNS, they cannot completely prevent disease or attenuate the illness if given too late following exposure. Smallpox antivirals are needed for treatment or post-exposure prophylaxis. Early results from laboratory studies suggest that the drug cidofovir may fight against the smallpox virus. (In 1996, the Food and Drug Administration [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 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.
Since 2001, NIAID has successfully transitioned two smallpox therapeutics to BARDA. NIAID has supported the antiviral ST-246 through Phase II clinical development. For more information on ST-246, please see Steps Towards a Smallpox Treatment.
NIAID has also supported CMX001 beginning with discovery and extending through preclinical research and completion of three Phase I studies. CMX-001 is a potential broad-spectrum antiviral agent with promising activity against all classes of double-stranded DNA (dsDNA) viruses that can infect humans, including herpes, adeno and polyoma viruses.
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Last Updated November 29, 2011