by Bill Snyder
Vanderbilt University Medical Center (VUMC) has joined an international effort to streamline and accelerate development of vaccines and other treatments against a growing worldwide surge of deadly and debilitating viral infections.
The Viral Immunotherapeutic Consortium (VIC), led by La Jolla Institute for immunology professor Erica Ollmann Saphire, PhD, is supported by a five-year, $35-million grant through the Centers for Excellence in Translational Research (CETR) program of the National Institute for Allergy and Infectious Diseases.
“The recent resurgence of Lassa, the difficulties in containing Ebola outbreaks and the re-emergence of alphaviruses in multiple locations including the United States make the development of therapies against these threats an urgent local and global concern,” Saphire said in a news release.
The VUMC effort is led by James Crowe Jr., MD, director of the Vanderbilt Vaccine Center, Ann Scott Carell Professor in the Department of Pediatrics and professor of Pediatrics and Pathology, Microbiology and Immunology in the Vanderbilt University School of Medicine.
“We’re excited to be leading the alphavirus antibody discovery program in this consortium,” Crowe said. “This is a challenging set of viruses that infect the brain or the joints, and currently there is very little we can do as medical providers for these patients.”
Crowe and his colleagues participate in two other CETRs aimed at combating the hemorrhagic fever viruses Ebola and Marburg, as well as another virus family that includes the highly fatal Nipah and Hendra viruses.
The VIC draws on the success of the Viral Hemorrhagic Fever Immunotherapeutic Consortium, which Saphire initiated and directed, and which led to an antibody cocktail that is being tested as a potential treatment for Ebola.
The new consortium will focus on clinical development of therapeutic candidates for two classes of deadly viruses represented by Ebola and Lassa, as well as alphaviruses such as chikungunya and equine encephalitis viruses that sicken millions of people around the world.
For several years Saphire, who will lead the Ebola project, has worked with Crowe and his team to improve the ability of antibodies to identify and destroy Ebola and a related virus, Marburg, by recognizing specific glycoproteins on the surfaces of the viral particles.
Crowe and his lab have developed high-efficiency methods to quickly isolate and generate large quantities of human monoclonal antibodies from the blood of people who survived outbreaks of Ebola and other deadly viral infections.
In turn, Saphire and her colleagues determined the molecular structure of the Ebola surface protein, a scientific feat that should aid the design of effective vaccines and antibody treatments against Ebola, which has a 50 percent mortality rate.
Since 2014 more than 11,000 people in West Africa have died from Ebola infections. A current outbreak that began last August in the Democratic Republic of the Congo so far has claimed more than 1,100 lives, according to the World Health Organization.
Although less well-known than Ebola, Lassa infects thousands of people in Africa annually. Like Ebola, Lassa can cause massive internal bleeding that can lead to shock and death. Children and women in late pregnancy are particularly vulnerable to Lassa virus infections, for which there are no vaccines or approved treatments.
Robert F. Garry Jr., PhD, at Tulane University School of Medicine in New Orleans, will guide clinical development of first-in-class human immunotherapies against multiple Lassa virus lineages.
Alphaviruses such as chikungunya and equine encephalitis viruses are largely transmitted by mosquitos and affect millions of people around the world. They can cause crippling pain and paralyzing encephalitis. Despite their epidemic potential, there are no existing therapies or licensed vaccines against any alphavirus.
Michael S. Diamond, MD, PhD, at Washington University School of Medicine in St. Louis, will lead the alphavirus project.
A scientific core led by Galit Alter, PhD, of the Ragon Institute of MGH, MIT and Harvard in Boston, will explore how antibodies generated by the three projects can be tailored to lessen the severity of viral infections.
Another core, led by Doug Lauffenburger, PhD, head of the Department of Biological Engineering at MIT, will develop ways of predicting which antibody features are most likely to confer protective activity.
The VIC will engage industry partners to accelerate translation of newly-developed therapeutics to the clinic.