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UrduNipah virus and the closely related Hendra virus are naturally found in Pteropid fruit bats (flying foxes) are capable of causing severe illness and death in a variety of domestic animals and humans. The strain of Nipah virus known as Nipah virus-Bangladesh, which is known to circulate in the Indian flying fox (Pteropus medius) populations in India and Bangladesh is particularly lethal, and this strain of Nipah virus was used in the study.
A major route of Nipah virus infection in humans is associated with the consumption of raw date palm sap contaminated by Pteropus bats or by direct exposure to infected animals, but person-to-person transmission can also occur. Currently there are no licensed vaccines or treatments for Nipah virus, although a human monoclonal antibody (mAb) targeting the Nipah virus and Hendra virus G glycoprotein spike, m102.4, has been employed in people on a compassionate use basis on some 18 occasions because of virus exposure and significant risk of infection. Here, Larry Zeitlin, Ph.D., cofounder and president, Mapp Biopharmaceutical Inc., San Diego, and study first and co-corresponding author aimed to improve mAb therapy for Nipah virus infection by testing m102.4 head-to-head with a mAb that targets the Nipah virus F glycoprotein spike, hu1F5.
The collaborative research team members are from Mapp Biopharmaceutical, the University of Texas Medical Branch (UTMB) and Galveston National Laboratory (GNL), the Uniformed Services University (USU), along with the University of Washington and Vanderbilt University Medical Center. Major support for this research was from a collaborative Center of Excellence for Translational Research (CETR) grant supported by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH) to Dr. Broder, Uniformed Services University.
In previous published work also supported by the CETR, the authors detailed the molecular interaction and structural details between this new mAb and the F glycoprotein and defined its virus-killing mechanism and its remarkable potency. In addition, extensive laboratory studies have indicated that neither Nipah virus nor Hendra virus appears capable of mutating and escaping from susceptibly to this mAb.
In experiments carried out in nonhuman primates at the GNL in Galveston, Texas, where there is a high-containment facility for working with live Nipah virus, the team of researchers, under the direction of Thomas W. Geisbert, Ph.D., professor, in the Department of Microbiology, UTMB and study co-corresponding author, demonstrated that hu1F5 conferred superior protection to m102.4 when administered to nonhuman primates as late as 5 days after virus infection, with all hu1F5-treated animals surviving Nipah virus challenge. Similar findings were also observed in hamsters. These data now strongly support the clinical development of mAb hu1F5 as a post-exposure prophylactic or therapeutic for Nipah virus infection, and likely also Hendra virus infection although studies with Hendra virus have yet to be conducted.
“Over the past nearly 15 years, my team in collaboration with the USU lab along with some of our other colleagues have conducted and published a host of studies on the therapeutic capacity of m102.4, but here we have shown for the very first time, that this new mAb could protect against fatal Nipah virus-Bangladesh infection, but remarkably can do so even when given the therapy much later after infection. What this means is that as far as people are concerned these latest findings strongly suggest that a potential treatment for Nipah virus infection is at hand,” said Dr. Geisbert.
“The remarkable success of this new hu1F5 mAb therapy against Nipah virus-Bangladesh infection and disease in a nonhuman primate is a key step towards its further clinical development as an effective therapeutic for use in people,” according to Christopher C. Broder, Ph.D., professor of Microbiology at USU and also study co-corresponding author, who’s laboratory generated the original antibody. Dr. Broder’s views are not representative of USU or the Department of Defense.
“Right now, there are no other effective therapeutic options for Nipah virus or Hendra virus infection,” according to Dr. Zeitlin. “Indeed, in light of these new data on hu1F5, and from our extensive experience in developing mAb-based therapies to highly pathogenic viruses, we are presently working towards taking hu1F5 to the clinic as a new therapeutic option for human Nipah virus infection. We anticipate starting Phase 1 safety testing in human volunteers this year.”
Nipah virus and Hendra virus, members of the paramyxovirus family, are highly infectious agents that emerged from flying foxes in the mid and late 1990s respectively, that have since caused serious disease outbreaks in humans and livestock in Australia, Malaysia, Singapore, Bangladesh and India. Nipah virus-Bangladesh is of particular concern because of its highly pathogenic nature and nearly yearly outbreaks in Bangladesh and India. “There are currently no licensed and approved vaccines or therapeutics for the prevention or treatment of infection and disease caused by these viruses for use in people,” said Dr. Broder. “This human mAb is a highly effective antiviral against Nipah virus, and likely Hendra virus as well, that has a real potential as an effective human therapeutic option.”
Other authors of this study include Robert W. Cross, Courtney Woolsey, Brandyn R. West, Viktoriya Borisevich, Krystle N. Agans, Abhishek N. Prasad, Daniel J. Deer, Lauren Stuart, Maria McCavitt-Malvido, Do H. Kim, James Pettitt, James E. Crowe Jr, Kevin J. Whaley, David Veesler, Antony Dimitrov, and Dafna M. Abelson.
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About the Uniformed Services University: The Uniformed Services University of the Health Sciences, founded by an act of Congress in 1972, is the nation’s federal health sciences university and the academic heart of the Military Health System. USU students are primarily active-duty uniformed officers in the Army, Navy, Air Force and Public Health Service who receive specialized education in tropical and infectious diseases, TBI and PTSD, disaster response and humanitarian assistance, global health, and acute trauma care. USU also has graduate programs in oral biology, biomedical sciences and public health committed to excellence in research. The University’s research program covers a wide range of areas important to both the military and public health. For more information about USU and its programs, visit www.usuhs.edu.
About the University of Texas Medical Branch: Texas’ first academic health center opened its doors in 1891 and today has four campuses, five health sciences schools, six institutes for advanced study, a research enterprise that includes one of only two national laboratories dedicated to the safe study of infectious threats to human health, a Level 1 Trauma Center and a health system offering a full range of primary and specialized medical services throughout the Texas Gulf Coast region. UTMB is an institution in the University of Texas System and a member of the Texas Medical Center.
About Mapp Biopharmaceutical: Mapp was founded in 2003 with a mission to develop monoclonal antibody drugs for neglected infectious diseases. For more information about Mapp and its pipeline, visit www.mappbio.com.
