Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Mice studies illustrate potential of chimp/human antibodies to protect against smallpox

25.01.2006


Results from a new study indicate that hybrid laboratory antibodies derived from chimpanzees and humans may provide a potentially safe and effective way to treat the serious complications that can occur following smallpox vaccination--and possibly may even protect against the deadly disease itself. The study, led by researchers with the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), appears online this week in the Proceedings of the National Academy of Sciences (PNAS).



A worldwide immunization program officially eradicated naturally occurring smallpox disease in 1980. However, concerns of a bioterror attack involving the highly contagious and fatal virus have prompted researchers to search for new smallpox vaccines and treatments.

The currently licensed smallpox vaccine consists of a live but weakened strain of vaccinia virus, a relative of the variola virus that causes smallpox. Vaccinia immunization has been proven effective in generating immunity against smallpox virus and other orthopoxviruses, including monkeypox and cowpox.


Although most reactions to the vaccinia virus are mild, the vaccine can cause serious and even life-threatening complications in individuals with weakened immune systems or skin conditions such as eczema, in infants younger than 12 months and in pregnant women. Health care providers currently treat smallpox vaccine complications with anti-vaccinia immune globulin (VIG)--pooled antibodies taken from the blood of individuals immunized with the smallpox vaccine. However, VIG is in short supply since the United States discontinued its public smallpox vaccination program in 1972.

NIAID-funded researchers have been working to develop alternatives to VIG based on antibodies they created in the laboratory. The study appearing online this week in PNAS details how senior authors Robert H. Purcell, M.D., co-chief of NIAID’s Laboratory of Infectious Diseases, and Bernard Moss, M.D., chief of NIAID’s Laboratory of Viral Diseases, and their collaborators developed hybrid antibodies from chimpanzees and humans that effectively inhibited the spread of both vaccinia and variola viruses in test tube experiments. Moreover, the hybrid antibodies proved more effective than VIG when tested in mice infected with vaccinia virus, even when given two days after virus exposure.

"This is an important finding in the race to develop effective measures against a potential bioterror attack involving the deadly smallpox virus," says NIH Director Elias A. Zerhouni, M.D.

"It is imperative that we have effective treatments available that everyone could use in the event of a bioterror attack," says NIAID Director Anthony S. Fauci, M.D. "This study shows that there are potential alternatives to existing treatments and perhaps to existing vaccines that we can use to enhance our arsenal of medical countermeasures."

Using a library of antibodies derived from the bone marrow of two vaccinia-immunized chimpanzees, the study researchers identified a pair of potent antibodies that target and neutralize the B5 protein, one of five key proteins responsible for cell-to-cell spread of infectious vaccinia virus. The researchers then combined the two chimp-derived antibodies with a human antibody to create two hybrid test antibodies, 8AH7AL and 8AH8AL. In test tube experiments, both antibody types prevented the spread of vaccinia virus. Further, the 8AH8AL antibody neutralized one strain of the smallpox-causing variola virus. The test involving the smallpox virus was performed at the Centers for Disease Control and Prevention in Atlanta.

The researchers then tested the effectiveness of the hybrid antibodies in mice. The control group--mice that were given the vaccinia virus but did not receive the antibodies--experienced continuous weight loss for five days after virus injection, which the researchers correlated with viral replication in the lungs. In contrast, mice injected with either of the two types of hybrid antibodies did not lose weight.

Since there was no difference in the protective abilities between the two hybrid antibodies, the researchers used 8AH8AL to determine the minimum effective dose. Groups of mice were given decreasing doses--90, 45 and 22.5 micrograms per mouse--of 8AH8AL or a single 5-mg dose of human VIG (two and a half times the recommended human dose on a weight basis) as a point of comparison. All five mice in the control group died or were sacrificed when their weight fell to 70 percent of their starting weight. All of the mice that were injected with 8AH8AL (even at the lowest dose) or with VIG were protected from death.

Further, mice that received a single 90-microgram dose of 8AH8AL two days after virus exposure experienced only slight weight loss followed by rapid recovery. Conversely, all five of the mice that received 5 mg of VIG 48 hours after virus exposure experienced much greater weight loss than those that received the hybrid antibody.

"This study demonstrated that the hybrid antibodies provide instant protection against the vaccinia virus and likely smallpox and are potentially more potent and more specific than the treatment we currently have available," says Dr. Purcell. The hybrid antibodies also offer a potentially significant advantage over VIG as a treatment for smallpox vaccination complications not only because VIG is in limited supply but because VIG lots may have different potencies and carry the potential to transmit other infectious agents, he adds.

According to Dr. Purcell, the hybrid antibodies should be tested in another animal model for effectiveness against the monkeypox virus, which closely mirrors smallpox but is less virulent in humans.

Currently, the smallpox virus exists in only two laboratories found in Atlanta, Georgia, and in Russia.

Kathy Stover | EurekAlert!
Further information:
http://www.niaid.nih.gov

More articles from Life Sciences:

nachricht Barium ruthenate: A high-yield, easy-to-handle perovskite catalyst for the oxidation of sulfides
16.07.2018 | Tokyo Institute of Technology

nachricht The secret sulfate code that lets the bad Tau in
16.07.2018 | American Society for Biochemistry and Molecular Biology

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

Im Focus: Chemical reactions in the light of ultrashort X-ray pulses from free-electron lasers

Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.

Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

Subaru Telescope helps pinpoint origin of ultra-high energy neutrino

16.07.2018 | Physics and Astronomy

Barium ruthenate: A high-yield, easy-to-handle perovskite catalyst for the oxidation of sulfides

16.07.2018 | Life Sciences

New research calculates capacity of North American forests to sequester carbon

16.07.2018 | Earth Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>