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National Institute of Allergy and Infectious Diseases
http://www.niaid.nih.gov/

FOR IMMEDIATE RELEASE
Sunday, July 11, 2004

CONTACT:
Jennifer Wenger
301-402-1663
jwenger@...


NEW METHOD ENABLES RESEARCHERS TO MAKE HUMAN SARS
ANTIBODIES QUICKLY

Human antibodies that thwart the SARS virus in mice can be
mass-produced quickly using a new laboratory technique
developed by an international research team collaborating
with the National Institute of Allergy and Infectious
Diseases (NIAID), one of the National Institutes of Health.
The new technique could become an important tool for
developing a cocktail of SARS-specific antibodies that
might help protect people recently exposed to the SARS
virus or at high risk of exposure. The technique could also
make possible the development of a similar approach to
prevent or treat other illnesses, such as HIV/AIDS and
hepatitis C.

The report describing these findings appears in the July
11, 2004, online issue of "Nature Medicine".

"While much has been accomplished in our quest for a
vaccine against SARS, a vaccine may provide little benefit
to someone already infected," says Anthony S. Fauci, M.D.,
director of NIAID. "Human SARS antibodies could offer a
double benefit: they could be used as a potent frontline
defense for health care workers and others at high risk of
exposure and as an effective treatment for those
individuals newly exposed to the virus." Currently, there
is no specific effective treatment for SARS.

SARS is caused by a coronavirus, a family of viruses named
for their spiky, crown-like appearance. Highly contagious,
SARS typically begins with flu-like symptoms, such as
fever, headache and muscle aches, and generally progresses
to pneumonia. In the 2003 global outbreak, more than 8,000
people were infected with SARS, 9 percent of whom died. In
April 2004, a small outbreak in China is suspected to have
begun as a result of negligent laboratory practices.

In the current study, Elisabetta Traggiai, Ph.D., and
Antonio Lanzavecchia, M.D., from the Institute for Research
in Biomedicine, Bellinzona, Switzerland, together with an
international research team, generated human antibodies
against SARS far more quickly and efficiently than with
current methods. Moreover, collaborators Kanta Subbarao,
M.D., and Brian Murphy, M.D., both in NIAID's Laboratory of
Infectious Diseases, demonstrated for the first time that
these human SARS antibodies, when injected into mice,
effectively prevent the virus from multiplying in the
respiratory system.

"The antibodies from people who have recovered from SARS
may target different parts of the virus than antibodies
generated by other animals, such as mice," says Dr.
Subbarao. "For this reason, human antibodies -- antibodies
from recovered patients that may have a proven
effectiveness in fighting the disease -- are considered most
desirable for a possible serotherapy against SARS."

Antibodies are made by special immune system cells called B
cells that, to do their job, must first be switched on. In
nature, this occurs when the body encounters a new or
repeat foreign "invader." In the laboratory, researchers
conventionally accomplish this by exposing the B cells to
Epstein Barr virus (EBV), a herpes virus that infects B
cells, which in turn activates them. Unfortunately, this
process is very inefficient, and only one or two B cells
out of one hundred are activated this way.

Dr. Lanzavecchia and his research team added a new
ingredient to the mix that significantly boosts efficiency.
Beginning with B cells from a recovered SARS patient, the
researchers added a short stretch of synthetic DNA that
mimics DNA found in bacteria and viruses. From 30 to 100
percent of the B cells -- in this case called "memory" B
cells because they had been exposed to the SARS virus
before -- were switched back on, enabling them to churn out
SARS antibodies at a fast pace. In only a few weeks, the
researchers screened hundreds of antibodies and obtained 35
that could neutralize the SARS virus in the laboratory. All
the neutralizing antibodies targeted a key SARS protein,
the spike protein, found on the virus surface.

Furthermore, when Drs. Subbarao and Murphy injected one of
the neutralizing antibodies into mice, they found that
these antibodies effectively thwarted the SARS virus from
multiplying in the lower respiratory tract, which includes
the lungs, and, to a lesser extent, in the upper
respiratory tract, which includes the nasal cavity.
According to Dr. Subbarao, these results are very promising
because replication of SARS in the lungs of humans can
result in pneumonia.

A primary benefit of the new activation technique is that
it generates a large pool of prospective antibodies from
which to choose, so only the most effective SARS fighters
can be chosen for use in a possible immune serum. Because
viruses can mutate, however, more than one antibody will
most likely be needed to achieve the optimal protection or
treatment, the researchers contend.

The researchers' next goal is to find additional antibodies
against the SARS virus, focusing on those that attach most
readily to the virus, are most potent against the virus,
and can attach to more than one site on the spike protein.
Before the antibodies might be made available for clinical
use, researchers need to test them for their effectiveness
in other laboratory animals, such as non-human primates, as
well as in human clinical trials.

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. Press releases,
fact sheets and other NIAID-related materials are available
on the NIAID Web site at <http://www.niaid.nih.gov>.

REFERENCE: E Traggiai et al. An efficient method to make
human monoclonal antibodies from memory B cells: potent
neutralization of SARS coronavirus. "Nature Medicine".
Published online July 2004. DOI: 10.1038/nm1080.

##

This NIH News Release is available online at:
http://www.nih.gov/news/pr/jul2004/niaid-11.htm

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