Monday, May 22, 2017

Cell: Researchers Identify Broadly Protective Antibodies In Ebola Survivor


Although the two most common strains of Ebola known to cause outbreaks are Ebola Zaire (EBOV) and Ebola Sudan (SUDV), three other strains have previously been identified; Bundibugyo ebolavirus (BDBV), the rarely seen Taï Forest ebolavirus (TAFV), and a strain found in the Philippines - not known to cause illness in humans - called Ebola Reston (RESTV) (see I'm Not Dying, I'm Just Reston).

This diversity complicates the creation of effective vaccines and/or therapeutics, since we can never be sure what version of Ebola will spark the next major outbreak. 
Last week researchers from Albert Einstein College of Medicine announced the discovery (as part of a multi-institutional research study) of 2 human antibodies (ADI-15878 & ADI-15742)  - out of a field of 349 distinct mAbs harvested from a survivor of the 2013-16 Ebola epidemic - that potently neutralized all five known Ebola viruses in tissue culture.

While there's still a great deal of work ahead, this discovery is hoped could eventually lead to a viable pan-Ebola treatment.  First the abstract, then a link to and some excerpts from the Albert Einstein College press release.

Antibodies from a Human Survivor Define Sites of Vulnerability for Broad Protection against Ebolaviruses
Anna Z. Wec10, Andrew S. Herbert10, Charles D. Murin, Elisabeth K. Nyakatura, Dafna M. Abelson, J. Maximilian Fels, Shihua He, Rebekah M. James, Marc-Antoine de La Vega, Wenjun Zhu, Russell R. Bakken, Eileen Goodwin, Hannah L. Turner, Rohit K. Jangra, Larry Zeitlin, Xiangguo Qiu, Jonathan R. Lai, Laura M. Walker, Andrew B. Ward, John M. Dye11,'Correspondence information about the author John M. DyeEmail the author John M. Dye, Kartik Chandran11,12,'Correspondence information about the author Kartik Chandran Email the author Kartik Chandran , Zachary A. Bornholdt11,13,'Correspondence information about the author Zachary A. Bornholdt

    •The human humoral response to Ebola virus contains broadly neutralizing antibodies
    •Potent pan-ebolavirus neutralizing antibodies recognize the viral fusion loop
    •The antibodies target viral entry intermediate generated in endosomes
    •The antibodies protect against three ebolaviruses that cause outbreaks in humans


Experimental monoclonal antibody (mAb) therapies have shown promise for treatment of lethal Ebola virus (EBOV) infections, but their species-specific recognition of the viral glycoprotein (GP) has limited their use against other divergent ebolaviruses associated with human disease.
Here, we mined the human immune response to natural EBOV infection and identified mAbs with exceptionally potent pan-ebolavirus neutralizing activity and protective efficacy against three virulent ebolaviruses. These mAbs recognize an inter-protomer epitope in the GP fusion loop, a critical and conserved element of the viral membrane fusion machinery, and neutralize viral entry by targeting a proteolytically primed, fusion-competent GP intermediate (GPCL) generated in host cell endosomes.
Only a few somatic hypermutations are required for broad antiviral activity, and germline-approximating variants display enhanced GPCL recognition, suggesting that such antibodies could be elicited more efficiently with suitably optimized GP immunogens. Our findings inform the development of both broadly effective immunotherapeutics and vaccines against filoviruses.

Researchers Discover First Human Antibodies That Work Against All Ebolaviruses

May 18, 2017—(BRONX, NY)—After analyzing the blood of a survivor of the 2013-16 Ebola outbreak, a team of scientists from academia, industry and the government has discovered the first natural human antibodies that can neutralize and protect animals against all three major disease-causing ebolaviruses. The findings, published online today in the journal Cell, could lead to the first broadly effective ebolavirus therapies and vaccines.


Broadly Active Therapeutics and Vaccines Needed

Monoclonal antibodies, which bind to and neutralize specific pathogens and toxins, have emerged as one of the most promising treatments for Ebola patients. A critical problem, however, is that most antibody therapies target just one specific ebolavirus. For example, the most advanced therapy—ZMappTM, a cocktail of three monoclonal antibodies—is specific for Ebola virus (formerly known as “Ebola Zaire”), but doesn’t work against two related ebolaviruses (Sudan virus and Bundibugyo virus) that have also caused major outbreaks.

“Since it’s impossible to predict which of these agents will cause the next epidemic, it would be ideal to develop a single therapy that could treat or prevent infection caused by any known ebolavirus,” says study co-leader Zachary A. Bornholdt, Ph.D., director of antibody discovery at Mapp Biopharmaceutical, Inc. “Our discovery and characterization of broadly neutralizing human antibodies is an important step toward that goal,” adds study co-leader, Kartik Chandran, Ph.D., professor of microbiology & immunology at Albert Einstein College of Medicine.

The study was also co-led by John M. Dye, Ph.D., chief of viral immunology at the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID).

(Continue . . . )

No comments: