|Scientists Find Antibody that Can Potently Neutralize
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.
This study was a collaboration with investigators Katharine N.
Bossart, Ph.D., and Lin-Fa Wang, Ph.D., from Geelong, Victoria,
Australia, where there is a high-level safety and security facility
for testing the antibody.
For more information on Dimitrov's laboratory at CCR Frederick,
please go to http://ccr.cancer.gov/staff/staff.asp?profileid=5749.
For more information about cancer, please visit the NCI Web site
or call NCI's Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).
NIAID is a component of the National Institutes of Health. 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 basic immunology,
transplantation and immune-related
The National Institutes of Health (NIH) — The Nation's
Medical Research Agency — includes 27 Institutes and
Centers and is a component of the U.S. Department of Health and
Human Services. It is the primary federal agency for conducting
and supporting basic, clinical and translational medical research,
and it investigates the causes, treatments, and cures for both
common and rare diseases. For more information about NIH and
its programs, visit www.nih.gov.
Zhu Z, Bossart K, Bishop KA, Grameri G, Dimitrov AS, McEachern JA, Feng Y, Middleton D, Wang L, Broder CC, Dimitrov DS. Exceptionally Potent Cross-Reactive Neutralization of Nipah and Hendra Viruses by a Human Monoclonal Antibody. The Journal of Infectious Diseases, February 15, 2008.