News and Research
Immune System
Mouse Antibodies Thwart SARS Virus

Genetic
material from the SARS virus, stained red, is shown in cells
lining the airways of mice. Image courtesy of Sherif R.
Zaki M.D., PhD., Centers for Disease Control and Prevention
3-15-2004
The mouse immune system develops antibodies capable of single-handedly
neutralizing the SARS virus, researchers at the National
Institute of Allergy and Infectious Diseases (NIAID) report
in the April 1 issue of the Journal of Virology, available
online March 12. NIAID is part of the National Institutes
of Health (NIH).
This
discovery affirms that researchers developing vaccines that
trigger antibodies to the SARS virus are heading in the
right direction. Vaccines can stimulate the immune system
to produce antibodies or specialized cells or both to stop
invading viruses.
"Since
SARS emerged in people in late 2002, global public health
experts have been anxiously awaiting a vaccine for this
potentially fatal respiratory ailment. Knowing which arm
of the immune system to trigger brings us one step closer
to that goal," says NIAID Director Anthony S. Fauci,
M.D.
"This
is good news for people developing vaccines that would prime
the immune system to produce antibodies against the SARS
virus," says Kanta Subbarao, M.D., an investigator
in NIAID's Laboratory of Infectious Diseases and lead author
on the study. "Our results also indicate that drug
researchers can use laboratory mice as a model to evaluate
whether a drug blocks SARS." Both findings could help
lessen the time it takes to develop an effective vaccine
or antiviral drugs for SARS.
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In collaboration with colleagues at the Centers for
Disease Control and Prevention and the NIH Clinical Center, Dr. Subbarao's
team examined whether mice could be infected with the SARS virus and
if so, how the mouse immune system responded. Initial experiments
revealed that while the SARS virus did not make the mice sick, it
was able to infect cells lining mouse airways and lungs to reproduce
itself.
Next, the NIAID team gave a subset of the mice a second
dose of the SARS virus 28 days later. This time they found that the
mice produced antibodies against the SARS virus and that the virus
did not replicate in the mice lungs and airways. The researchers concluded
that the first infection protected them from reinfection.
In their final experiment, the researchers tested
whether the antibodies the mice produced could be transferred to other
mice and protect them from infection. To do so, they transferred antibody-containing
serum from mice that had a previous SARS infection to uninfected mice.
When these uninfected mice were exposed to the SARS virus, the virus
was unable to replicate. This "passive immunity" demonstrated
that antibodies alone prevented the mice from becoming infected.
NIAID researchers are continuing their work to develop
a mouse model that more closely mimics SARS in people. The ideal laboratory
mouse for SARS studies would exhibit the same disease symptoms as
people so researchers could also use it to study how the illness progresses.
The present mouse model, however, will be very useful for evaluating
vaccines and antiviral drugs, Dr. Subbarao says.
The SARS virus infected 8,098 people and killed 774
worldwide between Nov. 1, 2002, and July 31, 2003, according to the
World Health Organization. For more information on SARS research,
see NIAID's updated fact sheet online at www.niaid.nih.gov/factsheets/sars.htm.
NIAID is a component of the National Institutes of
Health, an agency of the U.S. Department of Health and Human Services.
NIAID supports basic and applied research to prevent, diagnose and
treat infectious diseases such as HIV/AIDS and other sexually transmitted
infections, influenza, tuberculosis, malaria and illness from potential
agents of bioterrorism. NIAID also supports research on transplantation
and immune-related illnesses, including autoimmune disorders, asthma
and allergies.
Reference: K Subbarao et al. Prior infection and passive
transfer of neutralizing antibody prevent replication of severe acute
respiratory syndrome coronavirus in the respiratory tract of mice.
Journal of Virology DOI: 10.1128/JVI.78.7.000-000.2004. Available
online on 12 March.
Press releases, fact sheets and other NIAID-related
materials are available on the NIAID Web site at www.niaid.nih.gov.
This article has been adapted from a news release
issued by NIH/National Institute Of Allergy And Infectious Diseases,
www.niaid.nih.gov.
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