Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Research team develops nonhuman primate model of smallpox infection

05.10.2004


Scientists have made significant progress in developing an animal model of smallpox that closely resembles human disease, which will be necessary for testing of future vaccines and potential treatments.



The study, published in this week’s online early edition of Proceedings of the National Academy of Sciences, is the first to demonstrate that variola virus, the causative agent of smallpox, can produce lethal disease in monkeys.

Smallpox, a devastating disease, was eradicated in 1979 through the efforts of the World Health Organization (WHO). Currently, infectious variola is known to exist only in two WHO-sanctioned repositories, one in Russia and the other at the Centers for Disease Control and Prevention (CDC) in Atlanta. However, there is concern that undisclosed reference stocks of the virus may exist, and the U.S. population is no longer routinely immunized against the disease. Due to its potential as an agent of bioterrorism, antiviral drugs and an improved smallpox vaccine are urgently needed.


Because the disease no longer occurs naturally, vaccine and drug candidates cannot be tested for their ability to prevent or treat smallpox in humans. Thus, licensing of future medical countermeasures for smallpox will depend upon animal studies. The U.S. Food and Drug Administration (FDA) has established an animal efficacy rule to facilitate the approval of vaccines and drugs for biological agents in cases where efficacy data in humans cannot be obtained.

In 1999, a study group convened by the U.S. Institute of Medicine recommended that variola research be conducted, and a research plan was approved by the WHO to develop an animal model of the disease. Peter B. Jahrling of the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) led the research team.

Jahrling and his colleagues exposed 36 cynomolgous monkeys to one of two variola strains, Harper and India 7124. Eight animals were challenged by a combination of aerosol plus intravenous inoculation--four with Harper strain and four with India strain. The remaining 24 animals were exposed only by the intravenous route to varying doses of the virus.

Both variola strains produced severe disease, with almost uniform lethality and end-stage lesions resembling the human disease, in monkeys exposed by the combined route of infection. According to the authors, death usually occurred within six days of inoculation. Similar results were seen in monkeys that received the same dose of either virus by the intravenous route alone.

Having demonstrated that it was possible to achieve lethal infection of primates using variola virus, the team next tried to determine whether lower doses of virus would produce a less accelerated disease course. In order to more closely mimic human smallpox, the animal model would include near uniform mortality, but a longer mean time to death. Using a ten-fold lower dose, however, also resulted in lower mortality overall, so further refinement of the model is indicated.

"Despite its limitations," the authors wrote, "the intravenous variola primate model…has already provided valuable insight into the pathogenesis of this exquisitely adapted human pathogen." In a related article in the same journal, Rubins and her colleagues examined the host gene expression patterns of hemorrhagic smallpox in these animals. Specifically, they documented fluctuations in cellular proliferation, interferon, and viral modulation of the immune response. A better understanding of the disease process that occurs with smallpox infection will aid in the development of diagnostic and therapeutic approaches.

"Aside from the technical accomplishments, what’s notable about these studies is the collaboration between multiple agencies--including the Department of Defense and the academic sector--to address the issues raised in the 1999 Institute of Medicine report on the need to retain live variola virus," said co-author James W. LeDuc of the CDC, where the variola research was conducted. "This report has been the basis for the national smallpox research agenda, and these papers are the first significant publications to come from those efforts."

In addition to Jahrling and LeDuc, the research team included Lisa E. Hensley, John W. Huggins, and Mark J. Martinez of USAMRIID, and Kathleen H. Rubins and David A. Relman of Stanford University.

Caree Vander Linden | EurekAlert!
Further information:
http://www.usamriid.army.mil

More articles from Life Sciences:

nachricht Mass spectrometry sheds new light on thallium poisoning cold case
14.12.2018 | University of Maryland

nachricht Protein involved in nematode stress response identified
14.12.2018 | University of Illinois College of Agricultural, Consumer and Environmental Sciences

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Data use draining your battery? Tiny device to speed up memory while also saving power

The more objects we make "smart," from watches to entire buildings, the greater the need for these devices to store and retrieve massive amounts of data quickly without consuming too much power.

Millions of new memory cells could be part of a computer chip and provide that speed and energy savings, thanks to the discovery of a previously unobserved...

Im Focus: An energy-efficient way to stay warm: Sew high-tech heating patches to your clothes

Personal patches could reduce energy waste in buildings, Rutgers-led study says

What if, instead of turning up the thermostat, you could warm up with high-tech, flexible patches sewn into your clothes - while significantly reducing your...

Im Focus: Lethal combination: Drug cocktail turns off the juice to cancer cells

A widely used diabetes medication combined with an antihypertensive drug specifically inhibits tumor growth – this was discovered by researchers from the University of Basel’s Biozentrum two years ago. In a follow-up study, recently published in “Cell Reports”, the scientists report that this drug cocktail induces cancer cell death by switching off their energy supply.

The widely used anti-diabetes drug metformin not only reduces blood sugar but also has an anti-cancer effect. However, the metformin dose commonly used in the...

Im Focus: New Foldable Drone Flies through Narrow Holes in Rescue Missions

A research team from the University of Zurich has developed a new drone that can retract its propeller arms in flight and make itself small to fit through narrow gaps and holes. This is particularly useful when searching for victims of natural disasters.

Inspecting a damaged building after an earthquake or during a fire is exactly the kind of job that human rescuers would like drones to do for them. A flying...

Im Focus: Topological material switched off and on for the first time

Key advance for future topological transistors

Over the last decade, there has been much excitement about the discovery, recognised by the Nobel Prize in Physics only two years ago, that there are two types...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

ICTM Conference 2019: Digitization emerges as an engineering trend for turbomachinery construction

12.12.2018 | Event News

New Plastics Economy Investor Forum - Meeting Point for Innovations

10.12.2018 | Event News

EGU 2019 meeting: Media registration now open

06.12.2018 | Event News

 
Latest News

Data use draining your battery? Tiny device to speed up memory while also saving power

14.12.2018 | Power and Electrical Engineering

Tangled magnetic fields power cosmic particle accelerators

14.12.2018 | Physics and Astronomy

In search of missing worlds, Hubble finds a fast evaporating exoplanet

14.12.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>