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Wednesday, October 19, 2011
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Ken Pekoc
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Antibody treatment protects monkeys from Hendra virus disease

NIH-supported group exploring whether protection extends to Nipah virus disease

A human antibody given to monkeys infected with the deadly Hendra virus completely protected them from disease, according to a study published by National Institutes of Health (NIH) scientists and their collaborators. Hendra and the closely related Nipah virus, both rare viruses that are part of the NIH biodefense research program, target the lungs and brain and have human case fatality rates of 60 percent and more than 75 percent, respectively. These diseases in monkeys mirror what happens in humans, and the study results are cause for hope that the antibody, named m102.4, ultimately may be developed into a possible treatment for people who become infected with these viruses.

In May 2010, shortly after the NIH study in monkeys successfully concluded, Australian health officials requested m102.4 for emergency use in a woman and her 12-year-old daughter. They had been exposed to Hendra virus from an ill horse that ultimately was euthanized. Both the woman and child survived and showed no side effects from the treatment.

"This is an important research advance that illustrates how scientific discoveries emerge through a steady stepwise process, and how our investment in research on countermeasures for biodefense and emerging infectious diseases can help global preparedness efforts," said Anthony S. Fauci, M.D., director of the NIHís National Institute of Allergy and Infectious Diseases (NIAID).

Hendra virus emerged in 1994 in Australia and primarily affects horses, which can spread the disease to humans. No person-to-person transmission of Hendra has been reported. Nipah virus emerged in 1998 in Malaysia, and also has been found in Bangladesh and India. Nipah appears to infect humans more easily than Hendra and can be transmitted from person to person.

The NIAID-supported study, which appears online in Science Translational Medicine, involved infecting 14 African green monkeys with a lethal dose of Hendra virus. Twelve of the monkeys then received two treatments with m102.4, one either at 10, 24, or 72 hours after being infected, and another 48 hours later. All 12 monkeys treated with the antibody survived. The two untreated control monkeys died eight days after being infected.

The findings are the result of a series of studies carried out by different research laboratories. A group from NIHís National Cancer Institute and the Uniformed Services University of the Health Sciences (USUHS) discovered m102.4 in 2006 and developed the antibody for use in laboratory research. USUHS and Australian collaborators then developed an animal study model of m102.4 in ferrets infected with Nipah virus; the University of Texas Medical Branch and USUHS developed a monkey study model of Hendra and Nipah infection; and together with investigators from Boston University and NIAIDís Rocky Mountain Laboratories (RML) designed and carried out the antibody trial in biosafety level-4 (BSL-4) laboratory space at RML. Because the Hendra and Nipah viruses are so deadly and there is no licensed vaccine or treatment for either of them, both viruses must be studied in maximum-containment BSL-4 laboratories.

The World Health Organization reports 475 human cases of Nipah through 2008, with 251 deaths. Through the same period, there have been seven human Hendra cases with four fatalities. There also have been many horse fatalities. In their study, the scientists cite a handful of other outbreaks of Hendra virus in horses since 2008. Since June 2011, there have been 18 outbreaks in Australia, primarily in Queensland and New South Wales, with the latest reported Oct. 10.

Both viruses are spread by fruit bats, commonly known as flying foxes, which are reservoirs for these viruses. The fruit bats, which are resistant to the diseases, are found primarily in Australia but have been found as far west as Africa, north to India and Pakistan, and east to the Philippines. Additional studies on m102.4 as a possible treatment and as a preventive vaccine for Nipah and Hendra virus infections are being planned.

NIAID conducts and supports research — at NIH, throughout the United States, and worldwide — to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov.

About the National Institutes of Health (NIH): 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. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

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Reference: K Bossart et al. A neutralizing human monoclonal antibody protects African Green monkeys from Hendra virus challenge. Science Translational Medicine. DOI: 10.1126/scitranslmed.3002901 (2011).

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