A collaborative research team from the Uniformed Services University of the Health Sciences (USU), Australian Animal Health Laboratory and National Cancer Institute, a component of the National Institutes of Health, reports a major step forward in the development of an effective therapy against two deadly viruses, Nipah virus and the related Hendra virus. The results of this finding appear Oct. 30, 2009, in the open access journal PLoS Pathogens at http://dx.plos.org/10.1371/journal.ppat.1000642.
Nipah and Hendra viruses are found in Pteropid fruit bats (flying foxes) and are characterized by their recent emergence as agents capable of causing illness and death in domestic animals and humans.
In experiments carried out in ferrets at the Australian Animal Health Laboratory in Geelong, Victoria, Australia, where there is a high-level safety and security facility for working with live Nipah and Hendra viruses, the team of researchers demonstrated that giving an anti-virus human monoclonal antibody therapy after exposure to Nipah virus protected the animals from disease.
"These findings are extremely encouraging and clearly suggest the potential that a treatment for Hendra virus infection in a similar manner should be possible, given the very strong cross-reactive activity this antibody has against Hendra virus," said Deborah Middleton, D.V.M., Ph.D., who directed the animal experiments at the Australian Animal Health Laboratory.
Recent earlier work at the National Cancer Institute and USU resulted in the discovery and development of a human monoclonal antibody, m102.4, which could attack a critical component of both the Nipah and Hendra viruses. Antibodies-proteins found in blood or other bodily fluids of vertebrates-are used by the immune system to identify and neutralize viruses and bacteria.
The study's corresponding authors are Christopher C. Broder, Ph.D., professor of microbiology at USU, and Katharine Bossart, Ph.D., a USU alumna, now an assistant professor in the Department of Microbiology, Boston University School of Medicine and an investigator at the National Emerging Infectious Diseases Laboratories Institute in Boston. The pair led a team of researchers to test the effectiveness of the new antibody therapy in animals. The experiments were supported in part by the National Institute of Allergy and Infectious Diseases, NIH. The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. provides research support and management capabilities to the research team.
"We now have good evidence that this antibody could save human lives and the insights offered about how it works also could potentially provide a starting point to developing tools for targeting other diseases," said study co-author Dimiter S. Dimitrov, Ph.D., senior biomedical research scientist at the National Cancer Institute.
Nipah and Hendra viruses, members of the henipavirus family, are highly infectious agents that emerged from flying foxes in the 1990s to cause serious disease outbreaks in humans and livestock in Australia, Bangladesh, India, Malaysia and Singapore. Recent outbreaks have resulted in acute respiratory distress syndrome and encephalitis, person-to-person transmission, and up to 75 percent case fatality rates among humans. Additionally, these properties could allow the viruses to be used as bioterror weapons.
Initial experiments by the researchers using ferrets found that m102.4 was well tolerated, exhibited no adverse effects and retained high neutralizing activity. The findings suggested that m102.4 could potentially be used as a preventive or post-exposure agent, a diagnostic probe or a research reagent.
Hendra virus re-emerged again in August 2009, resulting in the death of several horses and one human. During the outbreak, in a compassionate attempt to save a human life, an available low dose of m102.4 was administered to an individual with advanced encephalitic disease. Although there were no adverse side effects, the patient did not improve as the irreversible damage by the virus had already been done. Like other antimicrobials, the clinical success of this antibody will depend on dose and time of administration. As Hendra and Nipah viruses cause severe disease in humans, a successful application of this antibody as a post-exposure therapy will likely require early intervention.
"In order to make clinical use of this therapeutic antibody against Hendra or Nipah virus, larger amounts will need to be prepared under proper manufacturing guidelines, carefully evaluated again in animal models and safety tested for human use" said Dr. Broder.
Dr. Bossart noted, "We hope this demonstration of anti-viral activity will foster some immediate activities to facilitate further development for future use in humans."
"There are currently no licensed and approved vaccines or therapeutics for prevention and treatment of disease caused by these viruses for humans or livestock," said Dr. Broder. "This fully-human monoclonal antibody is the first antiviral agent against the Nipah and Hendra viruses that has a genuine potential for human therapeutic use."
"The generation of these antibodies as therapeutics could help control outbreaks in geographical regions susceptible to henipaviruses, and could turn information from a deadly pathogen into a benefit for mankind," said Dr. Dimitrov.