The National Institutes of Health (NIH) has awarded a five-year, $28 million grant to establish a new center for excellence to find an antibody "cocktail" to fight two types of viruses that cause severe hemorrhagic fever, including the deadly Ebola virus. The project involves researchers from 15 institutions, including Kartik Chandran, Ph.D., and Jonathan Lai, Ph.D., at Albert Einstein College of Medicine of Yeshiva University. Einstein will receive approximately $4 million of the total grant.
The project will be led by Erica Ollmann Saphire, Ph.D., professor at The Scripps Research Institute (TSRI). "It's a global collaboration," said Dr. Saphire. "Everyone in the field got on the same page to collaborate on a set of definitive experiments."
Ebola causes an extremely virulent disease that leads to death in 25 to 90 percent of cases. Outbreaks of the fast-moving virus, which spreads via the blood or other bodily fluids of an infected person, have occurred in Uganda and the Democratic Republic of Congo in recent years. Ebola, and its close relative, Marburg virus, are both filoviruses. The project will seek to advance treatments for these, as well as the Lassa, Jun-n and Machupo arenaviruses. No FDA-approved treatments exist for any of these pathogens.
Advancing Therapies Against Ebola
Monoclonal antibodies, a type of protein that can bind to and disable specific substances in the body, are currently thought to be the most effective form of antiviral treatment for Ebola and related viruses. In the last year, researchers have identified specific antibodies and cocktails of antibodies that effectively protect against Ebola virus and Lassa virus in animal models and have pioneered approaches to develop new antiviral antibodies and to assess their effectiveness.
"Our consortium represents an unprecedented soup-to-nuts effort to develop antibody therapeutics against hemorrhagic fever viruses," said Dr. Chandran, associate professor of microbiology & immunology and the Harold and Muriel Block Faculty Scholar in Virology at Einstein. "These products, when translated into clinical practice, will provide a much needed pre- or post-exposure therapy against some of the world's most lethal viruses."
Dr. Chandran will receive $2 million of the total grant and serve as co-director of the mechanistic virology core for this project, along with Yoshihiro Kawaoka, Ph.D., D.V.M., at the University of Wisconsin-Madison. "Our core will support all individual research projects within the consortium by assessing how well each antibody works and the mechanism by which it blocks infection. This will help us design antibody cocktails with the best chance of working in animals," said Dr. Chandran. His lab at Einstein carries out both basic and translational research on Ebola virus and identified an essential receptor that Ebola uses to enter cells and cause infection.
Developing Antibodies
Dr. Lai, an expert in antibody technologies at Einstein, will focus on discovering new immunotherapeutic candidates against the Sudan Ebola virus and Marburg virus. "We aim to fill critical gaps in the antibody pipeline against these specific filoviruses," said Dr. Lai, associate professor of biochemistry, who will receive approximately $2 million of the grant. "More ambitiously, we will seek to develop antibodies that can target more than one filovirus species, or 'broadly neutralizing antibodies.' In other viruses, such as HIV-1 and influenza, such antibodies are critical for fighting or weakening infection. However, no broadly neutralizing antibodies exist against Ebola or Marburg."
"It is very exciting to be working with a large group of talented scientists, including those here at Einstein," continued Dr. Lai. "Together, we have a chance to make a real impact on prevention of these diseases."
In addition to those named above, the other institutions and scientists on the NIH National Institute of Allergy and Infectious Diseases (NIAID) Centers of Excellence for Translational Research (CETR) program grant, number U19AI109762, include: Gary Kobinger, Ph.D., at Public Health Agency of Canada, John Dye, Ph.D., at U.S. Army Medical Research Institute of Infectious Diseases, Leslie Lobel, M.D., Ph.D., at Ben Gurion University, Julius Lutwama, Ph.D., at Uganda Virus Research Institute, Robert Garry, Ph.D., and James Robinson, M.D., at Tulane University, Thomas Geisbert, Ph.D., at University of Texas Medical Branch, and Gene Olinger at NIAID. Biopharmaceutical companies on the grant include Mapp Biopharmaceutical (Larry Zeitlin), Zalgen Labs (Luis Branco) and Cangene (Cory Nykiforuk).
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