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Research

Variola virus (the virus that causes smallpox) causes disease only in people. Other pox-like viruses, such as monkeypox, can infect both animals and people. This unique characteristic of variola virus makes it an important virus to study and help us learn more about infectious diseases. Research using variola virus continues to expand our understanding of how viruses infect cells and how the immune system responds to infection.

The goal of smallpox research is to address three areas that are essential for public health:

  • Finding better antiviral drugs to treat smallpox disease.
  • Making safer vaccines.
  • Improving tests to detect variola virus.

All research using variola virus is overseen by the World Health Organization (WHO). The WHO Advisory Committee on Variola Virus Research reviews the research that is proposed each year. There are two WHO-designated sites where stocks of variola virus are stored and used for research: Centers for Disease Control and Prevention, Atlanta, Georgia, United States, and the Russian State Centre for Research on Virology and Biotechnology, Koltsovo, Novosibirsk Region, Russian Federation.

Research to Find New Treatment

Smallpox disease is caused by a virus. Drugs that fight diseases caused by viruses are called antiviral drugs. Some antivirals that may help to treat smallpox or prevent it from getting worse include tecovirimat, cidofovir, and brincidofovir. However, these drugs have not been tested in people sick with smallpox, so it is not known if a person with smallpox will benefit from treatment with any one of them.

There is only one antiviral drug, tecovirimat (TPOXX), approved by the U.S. Food and Drug Administration (FDA) in July 2018 for treatment of smallpox. Tecovirimat was approved under the FDA’s Animal Rule, which allows efficacy findings from adequate and well-controlled animal studies to support an FDA approval when it is not feasible or ethical to conduct efficacy trials in humans.

CDC is working with collaborators to find new and existing drugs that can reduce the harmful effects of variola virus. Scientists first look at each drug’s ability to stop infection in a laboratory. Then, they find out how the drug stops infection from happening. What they learn will help us understand how to stop variola viruses from spreading and to design better drugs to treat these viruses.

Research to Make Safer Vaccines

CDC also is collaborating with vaccine manufacturers to make new, safer vaccines and determine how well they work. Since these safer vaccines have never been used in an area with widespread smallpox disease, scientists cannot directly study their ability to prevent smallpox. Instead, scientists measure the effectiveness of new smallpox vaccines using indirect methods. They conduct clinical trials in which volunteers agree to be vaccinated with the new vaccines and provide blood samples. Scientists then take the blood samples, remove serum (the clear part of blood that contains substances called antibodies that fight disease), and test the serum’s ability to inactivate variola virus in laboratory.

Scientist also plan to study the new vaccines and drugs in mice and other animals. What they learn can give us a better idea of how well these vaccines might work in people.

Research to Make Better Tests

CDC also is conducting research to develop better lab tests to detect pox-like viruses more accurately because this would help diagnose smallpox in patients. If a smallpox emergency occurred, public health officials would need these tests to rapidly confirm a diagnosis of smallpox.

Want to learn more about smallpox disease?

Resources:

Damon IK, Damaso CR, McFadden G. Are We There Yet? The Smallpox Research Agenda Using Variola Virus. PLoS Pathog. 2014;10(5): e1004108. doi:10.1371/journal.ppat.1004108.

Kondas AV, Olson VA, Li Y, et al. Variola virus-specific diagnostic assays: characterization, sensitivity, and specificity. J Clin Microbiol. 2015;53:1406–1410.

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