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 Designer cells: artificial enzyme can activate a gene switch
22.05.2018 | Universität Basel

nachricht Flow of cerebrospinal fluid regulates neural stem cell division
22.05.2018 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

Im Focus: Dozens of binaries from Milky Way's globular clusters could be detectable by LISA

Next-generation gravitational wave detector in space will complement LIGO on Earth

The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...

Im Focus: Entangled atoms shine in unison

A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.

The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...

Im Focus: Computer-Designed Customized Regenerative Heart Valves

Cardiovascular tissue engineering aims to treat heart disease with prostheses that grow and regenerate. Now, researchers from the University of Zurich, the Technical University Eindhoven and the Charité Berlin have successfully implanted regenerative heart valves, designed with the aid of computer simulations, into sheep for the first time.

Producing living tissue or organs based on human cells is one of the main research fields in regenerative medicine. Tissue engineering, which involves growing...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

 
Latest News

Matabele ants: Travelling faster with detours

22.05.2018 | Life Sciences

Flow of cerebrospinal fluid regulates neural stem cell division

22.05.2018 | Life Sciences

Chemists at FAU successfully demonstrate imine hydrogenation with inexpensive main group metal

22.05.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>