Antibody that Can Potently Neutralize Viruses

Mar 7, 2008
In laboratory experiments, scientists at the National
Cancer Institute (NCI), part of the National Institutes of
Health (NIH), and their colleagues supported by the NIH
National Institute of Allergy and Infectious Disease
(NIAID), have discovered an antibody that neutralizes two
viruses classified as henipaviruses.

Nipah virus (NiV) and Hendra virus (HeV) are highly
infectious agents that transitioned from infecting flying
foxes in the mid-1990s to causing fatal disease in humans
and livestock in Australia, Bangladesh, India, Malaysia,
and Singapore. Recent outbreaks have resulted in
encephalitis and acute respiratory distress,
person-to-person transmission, and up to 70 percent
fatality rates. The finding appears in the Feb. 15, 2008,
issue of The Journal of Infectious Diseases.

Antibodies are proteins that are found in blood or other
bodily fluids of vertebrates and are used by the immune
system to identify and neutralize foreign molecules,
including bacteria and viruses. According to study author
Dimiter S. Dimitrov, Ph.D., of NCI's Center for Cancer
Research in Frederick, Md., "We hope that with further
research this antibody can save human lives. The insights
offered about how it works also could potentially provide a
starting point for the development of tools for targeting
other diseases."

The first step in countering infections caused by these
viruses is to find antibodies that can neutralize them.
Viral neutralization is the process by which an antibody
alone or an antibody plus another molecule, called
complement, block the infectivity of a virus.

Zhongui Zhu, Ph.D., of Dimitrov's group and their
NIAID-supported collaborator Christopher Broder, Ph.D., of
the Uniformed Services University of the Health Sciences,
Bethesda, Md., had previously identified antibodies to NiV
and HeV by panning a large antibody library against a
soluble form of the protein that makes up the HeV shell.
One of these antibodies, m102, exhibited a strong ability
to neutralize both NiV and HeV.

In their current experiment, the researchers created an
improved version of m102, called m102.4, by using a complex
procedure called in vitro maturation. The m102.4 version is
even more potent than its parent antibody, m102, and can
neutralize both HeV and NiV without a loss of
cross-reactivity, which is the ability of an antibody that
is specific for one target, or antigen, to bind to a second
antigen. The researchers believe that the m102.4 clone is
the first fully human antibody that is capable of potently
neutralizing both HeV and NiV.

Their results suggest that m102.4 may prove useful as a
therapeutic for treatment of diseases caused by
henipaviruses. Their initial experiments in small mammals
called ferrets found that m102.4 was well tolerated,
exhibited no adverse effects, and retained high
neutralizing activity, which may point to this antibody's
potential for clinical use as a preventive agent, a
diagnostic probe, or an antiviral therapeutic.

"The generation of a potent antibody against both HeV and
NiV could help control outbreaks in geographical regions
susceptible to henipaviruses, and result in a benefit for
mankind," said Dimitrov. He also noted that the laboratory
technology they used for the maturation of antibodies is
being used for the development of antibodies against
cancer.

Source: NIH