VHFIC scientists identify novel antibodies against Marburgviruses

A new study led by scientists at The Scripps Research Institute (TSRI) identifies new antibodies that protect against deadly Marburg virus, which along with Ebola virus are two of the multiple filoviruses that cause deadly disease in humans. The research, published in the journal PloS Pathogens, provides components needed to develop treatments for future outbreaks. <http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1005016>

“These antibodies attack a new site on Marburg virus we had not seen before,” said Erica Ollmann Saphire, senior author of the new study, professor at TSRI and director of the Viral Hemorrhagic Fever Immunotherapeutic Consortium. The antibodies were developed though the academic-industrial partnership formed to discover and develop treatment for viruses like Marburg and Ebola.

In treatments like ZmappTM, used against Ebola virus, mixtures or “cocktails” of antibodies block the virus from infecting new cells and alert the immune system to the presence of the infection. Marburg virus is 70% different from Ebola virus, and requires a unique set of antibodies for medical defense. Antibodies against one site were revealed by Vanderbilt University and TSRI in February, but the complementary antibodies needed against other sites remained to be discovered. In this work, Integrated Biotherapeutics, Mapp Bio and Emergent Biosciences worked with TSRI to draw out antibodies against different sites.

Some of the new antibodies target a new site on Marburg virus not seen before, a “wing”-like feature attached to the base of the molecule. Antibodies against this newly discovered site protect 90-100% of infected animals from lethal infection. Other antibodies discovered in the study are able to cross-react not only among strains of Marburg virus, but also the five different ebolaviruses.

There have been multiple outbreaks of Marburg virus in Africa this decade, some of which killed up to 90% of the people infected. Adventure travelers have also returned to the US and Europe with the disease. “We expect Marburg virus to emerge again, and to acquire new mutations” said TSRI Research Assistant Marnie Fusco, first author of the study. “The cross-reactive antibodies could be used as diagnostics for newly emerging strains.”

“The high cost of creating independent vaccines or treatments for each of the different viruses in this family necessitates intelligent design of immunogens,” added scientist Jody Berry who initiated the study with Saphire six years ago.  “The molecular images used to design the molecules and evaluate the antibodies point the way forward.”

In addition to Saphire, Berry, and Fusco, authors of the study include Dr. Javad Aman, Kelly Warfield, Fredrick Holtsberg, Sergey Shulenin, and Hong Vu of Integrated Biotherapeutics in Gaithersburg, Maryland, Dr. Gene Olinger and Julia Biggins of USAMRIID and NIAID in Frederick, Maryland, Dr. Cory Nykiforuk and Robyn Cassan of Emergent Biosciences in Winnipeg, Manitoba; Dr. Sheng Li of The University of California, Dr. Andrew Ward, Dr. Takao Hashiguchi, and Daniel Murin of the The Scripps Research Institute and Drs. Larry Zeitlin and Kevin Whaley of Mapp Biotherapeutics in San Diego.