Featured Research

from universities, journals, and other organizations

Research Team Develops Nonhuman Primate Model Of Smallpox Infection

Date:
October 6, 2004
Source:
U.S. Army Medical Research Institute Of Infectious Diseases
Summary:
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.

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.

###

USAMRIID, located at Fort Detrick, Maryland, is the lead medical research laboratory for the U.S. Biological Defense Research Program, and plays a key role in national defense and in infectious disease research. The Institute's mission is to conduct basic and applied research on biological threats resulting in medical solutions (such as vaccines, drugs and diagnostics) to protect the warfighter. USAMRIID is a subordinate laboratory of the U.S. Army Medical Research and Materiel Command.

References:

Jahrling, P.B., Hensley, L.E., Martinez, M.J., LeDuc, J.W., Rubins, K.H., Relman, D.A., Huggins, J.W. 2004. Exploring the potential of variola virus infection of cynomolgus macaques as a model for human smallpox. Proceedings of the National Academy of Sciences (online edition).

Rubins, K. H., Hensley, L.E., Jahrling, P.B., Whitney, A. R., Geisbert, T.W., Huggins, J.W., Owen, A., LeDuc, J.W., Brown, P.O., Relman, D.A. 2004. The host response to smallpox: Analysis of the gene expression program in peripheral blood cells in a nonhuman primate model. Proceedings of the National Academy of Sciences (online edition).


Story Source:

The above story is based on materials provided by U.S. Army Medical Research Institute Of Infectious Diseases. Note: Materials may be edited for content and length.


Cite This Page:

U.S. Army Medical Research Institute Of Infectious Diseases. "Research Team Develops Nonhuman Primate Model Of Smallpox Infection." ScienceDaily. ScienceDaily, 6 October 2004. <www.sciencedaily.com/releases/2004/10/041006085227.htm>.
U.S. Army Medical Research Institute Of Infectious Diseases. (2004, October 6). Research Team Develops Nonhuman Primate Model Of Smallpox Infection. ScienceDaily. Retrieved September 19, 2014 from www.sciencedaily.com/releases/2004/10/041006085227.htm
U.S. Army Medical Research Institute Of Infectious Diseases. "Research Team Develops Nonhuman Primate Model Of Smallpox Infection." ScienceDaily. www.sciencedaily.com/releases/2004/10/041006085227.htm (accessed September 19, 2014).

Share This



More Plants & Animals News

Friday, September 19, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Raw: Elephant Undergoes Surgery in Tbilisi Zoo

Raw: Elephant Undergoes Surgery in Tbilisi Zoo

AP (Sep. 18, 2014) Grand the elephant has successfully undergone surgery to remove a portion of infected tusk at Tbilisi Zoo in Georgia. British veterinary surgeons used an electric drill to extract the infected piece. (Sept. 18) Video provided by AP
Powered by NewsLook.com
Chimp Violence Study Renews Debate On Why They Kill

Chimp Violence Study Renews Debate On Why They Kill

Newsy (Sep. 17, 2014) The study weighs in on a debate over whether chimps are naturally violent or become that way due to human interference in the environment. Video provided by Newsy
Powered by NewsLook.com
Some Tobacco Farmers Thrive Amid Challenges

Some Tobacco Farmers Thrive Amid Challenges

AP (Sep. 16, 2014) The South's tobacco country is surviving, and even thriving in some cases, as demand overseas keeps growers in the fields of one of America's oldest cash crops. (Sept. 16) Video provided by AP
Powered by NewsLook.com
Scientists Given Rare Glimpse of 350-Kilo Colossal Squid

Scientists Given Rare Glimpse of 350-Kilo Colossal Squid

AFP (Sep. 16, 2014) Scientists say a female colossal squid weighing an estimated 350 kilograms (770 lbs) and thought to be only the second intact specimen ever found was carrying eggs when discovered in the Antarctic. Duration: 00:47 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins