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 A Map of the Cell’s Power Station
18.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

nachricht On the way to developing a new active ingredient against chronic infections
21.08.2017 | Deutsches Zentrum für Infektionsforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

Nagoya physicists resolve long-standing mystery of structure-less transition

21.08.2017 | Materials Sciences

Chronic stress induces fatal organ dysfunctions via a new neural circuit

21.08.2017 | Health and Medicine

Scientists from the MSU studied new liquid-crystalline photochrom

21.08.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>