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.
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.
Journal reference: 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.
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