A new treatment for the deadly Hendra virus has proven successful in primate tests -- a major step forward in combating the virus, which kills about 60 percent of those it infects and has been implicated in sporadic outbreaks in Australia ever since it was first identified in 1994.
Researchers from the University of Texas Medical Branch at Galveston, Rocky Mountain Laboratories, the National Institute of Allergy and Infectious Diseases, the National Institutes of Health, the Uniformed Services University of the Health Sciences, the National Cancer Institute, and the Boston University School of Medicine teamed up to develop and test the new therapy, in a project primarily supported by a grant awarded to UTMB professor Thomas Geisbert by the NIAID.
Experiments were conducted at RML in a biosafety level 4 "spacesuit" lab, because no licensed vaccine or therapy currently exists for Hendra. Researchers infected 14 African green monkeys -- chosen because their response to Hendra is very similar to that of humans -- with the virus. At varying time intervals after infection, 12 of the monkeys were then given doses of a human antibody designated m102.4, which had been specially selected for its affinity for Hendra.
Earlier test tube and small-animal experiments by USUHS professor Christopher Broder and colleagues in Australia had strongly suggested that m102.4 antibodies would bind to proteins on the surface of Hendra virus particles and block the process by which the virus invades cells. This turned out to be the case with the monkeys as well, and all 12 of the treated animals survived -- including a group not given their first dose of antibodies until three days after infection with Hendra.
"I think this is a very promising therapy, especially when you consider that it was still strong three days later," said Geisbert, one of the lead authors of a paper on the work published online Oct. 19 in Science Translational Medicine. "What's also interesting is that this antibody has strong activity against Nipah virus as well, which is extremely similar to Hendra."
Both Hendra and Nipah primarily reside in fruit bats, and both are extraordinarily dangerous to humans. (If the virus names sound familiar to moviegoers, it's not an accident: director Stephen Soderbergh used an imaginary combination between Hendra and Nipah to create the virus in the recent film Contagion.) But while Hendra primarily affects horses, which can spread the disease to humans, Nipah has evolved to be transmissible directly from human to human. First identified in Malaysia in 1998, Nipah is blamed for 251 deaths in outbreaks in Malaysia, India and Bangladesh.
"Here at UTMB's Galveston National Laboratory we're currently looking at the efficacy of this antibody against Nipah," Geisbert said. "That would make it even more valuable."
Last year m102.4 was requested for emergency use in Australia to protect a woman and her daughter from an exposure to Hendra. Both survived and showed no side effects from the treatment.
Much more extensive testing would be required, though, to obtain approval for m102.4 as a therapy. According to GNL director James LeDuc, the facility is well prepared to move forward with such efforts.
"Collaboration between federal and university scientists has been instrumental in producing this novel breakthrough," LeDuc said. "We're ready to help in the next steps in translating this discovery into a usable treatment."
- K. N. Bossart, T. W. Geisbert, H. Feldmann, Z. Zhu, F. Feldmann, J. B. Geisbert, L. Yan, Y.-R. Feng, D. Brining, D. Scott, Y. Wang, A. S. Dimitrov, J. Callison, Y.-P. Chan, A. C. Hickey, D. S. Dimitrov, C. C. Broder, B. Rockx. A Neutralizing Human Monoclonal Antibody Protects African Green Monkeys from Hendra Virus Challenge. Science Translational Medicine, 2011; 3 (105): 105ra103 DOI: 10.1126/scitranslmed.3002901
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