Creative Minds: Preparing for Future Pandemics
Posted on by Dr. Francis Collins
Growing up in Queens, NY, Jonathan Abraham developed a love for books and an interest in infectious diseases. One day Abraham got his hands on a copy of Laurie Garrett’s The Coming Plague, a 1990s bestseller warning of future global pandemics, and he sensed his life’s calling. He would help people around the world survive deadly viral outbreaks, particularly from Ebola, Marburg, and other really bad bugs that cause deadly hemorrhagic fevers.
Abraham, now a physician-scientist at Brigham and Women’s Hospital, Boston, continues to chase that dream. With support from an NIH Director’s 2016 Early Independence Award, Abraham has set out to help design the next generation of treatments to enable more people to survive future outbreaks of viral hemorrhagic fever. His research strategy: find antibodies in the blood of known survivors that helped them overcome their infections. With further study, he hopes to develop purified forms of the antibodies as potentially life-saving treatments for people whose own immune systems may not make them in time. This therapeutic strategy is called passive immunity.
Already, Abraham has begun collecting blood samples from survivors of Ebola, Marburg, and other hemorrhagic fevers. The next step—and it can be a long and tedious one—is to isolate the B immune cells that produce the antibodies responsible for fighting each of the viruses. When he finds one, Abraham will then identify and sequence the specific immunoglobulin genes encoding those antibodies in the appropriate B cell.
Having those DNA sequences in hand, Abraham can make large quantities of the antibodies, allowing him to study their ability to neutralize the viruses in lab dishes and infected animals. Using X-ray crystallography and cryo-electron (Cryo-EM) microscopy, he’ll also explore the structure of those antibodies in unprecedented detail.
Abraham recently reported some success in detailing the structure of the Junín virus bound to a neutralizing antibody . Junín virus is endemic to north-central Argentina, where annual outbreaks occur and lead to a deadly hemorrhagic fever. It is also a virus for which transfusion of a survivor’s immune plasma—including its neutralizing antibodies—is already an established treatment. In fact, when people receive these infusions, their chances of dying from the infection drop to less than 1 percent.
Abraham hopes that structural comparisons of the protective antibodies will help to explain the inherent differences and similarities in triggering passive immunity in each of the infections under study. Knowing the similarities will point the way to promising new antibody-based treatments with potential to protect against multiple viruses. Abraham also wants to find ways to alleviate a mysterious and serious side effect of passive immunity treatment for Junín virus infection: 10 percent of treated survivors go on to develop a potentially fatal neurological syndrome, characterized by transient fevers and abnormal eye movement.
In the coming years, we can be certain that viral pandemics will continue to occur. Preparation remains vital, and Abraham and other scientists here in the United States and around the globe continue to work tirelessly to have the needed resources ready to fight the next viral pandemic.
 Molecular Basis for Antibody-Mediated Neutralization of New World Hemorrhagic Fever Mammarenaviruses. Mahmutovic S, Clark L, Levis SC, Briggiler AM, Enria DA, Harrison SC, Abraham J. Cell Host Microbe. 2015 Dec 9;18(6):705-713.
Hemorrhagic Fevers (MedlinePlus/National Library of Medicine/NIH)
Jonathan Abraham (Harvard Medical School, Boston, MA)
Abraham NIH Project Information (NIH RePORTER)
NIH Support: Common Fund
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Tags: antibodies, cryo-electron microscopy, cryo-EM, Ebola, hemorrhagic fever, infectious diseases, junin virus, Marburg virus, neutralizing antibodies, New World hemorrhagic fever, NIH Director’s 2016 Early Independence Award, pandemic, passive immunity, viral hemorrhagic fever, viral pandemics, virology, virus, x-ray crystallography