Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers discover new Ebola-fighting antibodies in blood of outbreak survivor

22.02.2016

A research team that included scientists from The Scripps Research Institute (TSRI) has identified a new group of powerful antibodies to fight Ebola virus.

The antibodies, isolated from the blood of a survivor of the 2014 Ebola outbreak and the largest panel reported to date, could guide the development of a vaccine or therapeutic against Ebola. The new study also revealed a previously unknown site of vulnerability in the structure of the deadly virus.


This image shows a key Ebola virus protein and vulnerable sites where antibodies (in color) can bind and neutralize it.

Image by Hannah Turner and Daniel Murin, courtesy of The Scripps Research Institute

"Our Science paper describes the first in-depth view into the human antibody response to Ebola virus," said team leader Laura Walker, senior scientist at Adimab, LLC, and an alumna of TSRI's PhD program. "Within weeks of receiving a blood sample from a survivor of the 2014 Ebola outbreak, we were able to isolate and characterize over 300 monoclonal antibodies that reacted with the Ebola virus surface glycoprotein."

Co-authors of the paper included TSRI lab heads Professor Erica Ollmann Saphire (also co-director of the Global Virus Network Center of Excellence at TSRI); Associate Professor Andrew Ward; and Professor Dennis Burton (also scientific director of the International AIDS Vaccine Initiative's (IAVI) Neutralizing Antibody Center and the National Institutes of Health (NIH)-sponsored Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID), both at TSRI).

The study was published February 18, 2016, in the journal Science.

Searching for Powerful Antibodies

Studies at TSRI and other institutions have shown that Ebola virus has several weak points in its structure where antibodies can target and neutralize the virus. However, the immune system typically needs a long period of trial and error to produce the right antibodies against these sites, so researchers have been working with only a small library of anti-Ebola options.

Despite this limited library, researchers have had some success in designing antibody "cocktails" that target several weak points at once. One treatment in development, Mapp Biopharmaceutical Inc.'s ZMapp™, is a cocktail of three mouse antibodies modified to resemble human antibodies. This treatment was successful in primate trials and used as an experimental human treatment in the 2014 outbreak.

With ZMapp showing promise, researchers are searching for additional antibodies to fight Ebola.

"These types of antibodies could be developed into different types of antibody cocktails or therapeutics, in addition to advancing vaccine design," said Ward.

Bringing New Technologies Together

The new study took advantage of a recently launched single B cell isolation platform from Adimab, which researchers used to quickly find more than 300 antibodies that reacted with the Ebola virus surface glycoprotein--the viral structure that fuses with host cells.

Researchers at TSRI and the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) then performed an in-depth analysis of the therapeutic potential of these antibodies. Crucial to this effort was the TSRI development of antigens--molecules that can "fish" for antibodies in blood serum.

"That's where our expertise came into play," said the study's first author Zachary Bornholdt, an assistant professor in the Ollmann Saphire lab at the time of the study and current associate director of antibody discovery at Mapp Biopharmaceutical.

Remarkably, 77 percent of the antibodies in the new study showed the potential to neutralize Ebola virus, and several antibodies demonstrated significant protection against the virus in mouse models. "We identified three highly protective antibodies that each targeted a different site--or epitope--on the Ebola virus glycoprotein," Bornholdt said.

Because these are human antibodies, not modified mouse antibodies, researchers potentially could quickly use them to design a treatment. Furthermore, with these new antibodies available, researchers might be able to design secondary treatments in case the Ebola virus mutates to escape other treatments.

Next, the researchers used an imaging technique, called electron microscopy, to investigate exactly where the antibodies were binding with Ebola virus. The imaging, led by the Ward lab at TSRI, revealed a previously unknown Achilles heel on the virus: a spot at the base of the Ebola virus surface glycoprotein.

While Ebola virus mutates rapidly, this site is part of the virus's larger machinery and tends to stay the same. This means targeting this spot could neutralize many strains of Ebola.

To encourage further studies, the researchers have made the genetic sequences of these antibodies available to the research community.

Stopping Emerging Diseases

The researchers believe the techniques in this study could be used to find treatments for other emerging diseases, such as Zika virus.

Bornholdt thinks of the new study as a test case. In just over a year, the combination of Adimab and TSRI methods led to the discovery of promising antibodies--and future experiments should move even more quickly now that researchers have experience with these tools.

"With other outbreaks, we could take blood samples from the first wave of survivors and potentially produce a therapeutic rapidly," said Bornholdt. "That's the long-term goal."

###

In addition to Walker, Ollmann Saphire, Ward, Burton and Bornholdt, authors of the study, "Isolation of potent neutralizing antibodies from a survivor of the 2014 Ebola virus outbreak," were Hannah L. Turner, Charles D. Murin, Devin Sok, Marnie L. Fusco and Kathleen B.J. Pommert of TSRI; Wen Li, Eric Krauland, Tillman U. Gerngross and Dane K. Wittrup of Adimab; Colby A. Souders, Lisa A. Cavacini, Heidi L. Smith, Mark Klempner and Keith A. Reimann of MassBiologics; Ashley E. Piper, Arthur Goff, Joshua D. Shamblin, Suzanne E. Wollen, Thomas R. Sprague and Pamela J. Glass of USAMRIID. To view the abstract, see http://science.sciencemag.org/content/early/2016/02/17/science.aad5788.abstract

This research was supported by the NIH (grants R01 AI067927, U19 AI109762), the NIH National Institute of Allergy and Infectious Diseases Center for Excellence in Translational Research (grant U19AI109762), a predoctoral fellowship from the National Science Foundation, the Defense Advanced Research Projects Agency (DARPA-BAA-13-03) and CHAVI-ID (grant UM1AI100663).

Media Contact

Madeline McCurry-Schmidt
madms@scripps.edu
858-784-9254

 @scrippsresearch

http://www.scripps.edu 

Madeline McCurry-Schmidt | EurekAlert!

Further reports about: Ebola virus Infectious Diseases Saphire TSRI human antibodies outbreak structure

More articles from Life Sciences:

nachricht Show me your leaves - Health check for urban trees
12.12.2017 | Gesellschaft für Ökologie e.V.

nachricht Liver Cancer: Lipid Synthesis Promotes Tumor Formation
12.12.2017 | Universität Basel

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Long-lived storage of a photonic qubit for worldwide teleportation

MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.

Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...

Im Focus: Electromagnetic water cloak eliminates drag and wake

Detailed calculations show water cloaks are feasible with today's technology

Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...

Im Focus: Scientists channel graphene to understand filtration and ion transport into cells

Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.

To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...

Im Focus: Towards data storage at the single molecule level

The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.

Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...

Im Focus: Successful Mechanical Testing of Nanowires

With innovative experiments, researchers at the Helmholtz-Zentrums Geesthacht and the Technical University Hamburg unravel why tiny metallic structures are extremely strong

Light-weight and simultaneously strong – porous metallic nanomaterials promise interesting applications as, for instance, for future aeroplanes with enhanced...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

AKL’18: The opportunities and challenges of digitalization in the laser industry

07.12.2017 | Event News

 
Latest News

Long-lived storage of a photonic qubit for worldwide teleportation

12.12.2017 | Physics and Astronomy

Multi-year submarine-canyon study challenges textbook theories about turbidity currents

12.12.2017 | Earth Sciences

Electromagnetic water cloak eliminates drag and wake

12.12.2017 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>