Scientists at the Scripps Research Institute (TSRI) have identified weak spots on the surface of Ebola virus that are targeted by the antibodies in ZMapp, the experimental drug cocktail administered to several patients during the recent Ebola outbreak. The study, led by TSRI structural biologists Andrew Ward and Erica Ollmann Saphire and published online ahead of print this week by the journal Proceedings of the National Academy of Sciences, provides a revealing 3-D picture of how the ZMapp antibodies bind to Ebola virus.
“The structural images of Ebola virus are like enemy reconnaissance,” says Saphire. “They tell us exactly where to target antibodies or drugs.”
Ward says, “Now that we know how ZMapp targets Ebola, we can compare all newly discovered anti-Ebola antibodies as we try to formulate an even better immunotherapeutic cocktail.”
ZMapp, developed by San Diego-based Mapp Biopharmaceutical, was used in August to treat several patients in the ongoing Ebola virus outbreak. Although five of the seven patients who received ZMapp survived, researchers cannot yet say for sure whether ZMapp made a difference in their recoveries.
The new study explains why ZMapp could have been effective. Using an imaging technique called electron microscopy, researchers found that two of the ZMapp antibodies bind near the base of virus, appearing to prevent the virus from entering cells. A third antibody binds near the top of the virus, possibly acting as a beacon to call the body’s immune system to the site of infection.
The new picture of ZMapp reveals the two antibodies that bind near the base of the virus seem to be competing for the same site. While this appears to be a particularly vulnerable spot on Ebola virus’s surface as identified in previous studies, one question now is whether future cocktails should continue to use two antibodies to target this site or try to attack the virus from a third angle.
“This information helps guide decisions about how to formulate these life-saving therapies,” says C. Daniel Murin, a graduate student in the labs of Ward and Saphire and first author of the new study. “Instead of including two different antibodies that do the same thing, why not use twice as much of the more effective one instead? Or include a third antibody against a different site to stop the virus a third way?”
Luckily, while the Ebola virus has undergone more than 300 genetic changes in the current outbreak (according to research published in the journal Science in August), the new study indicates the sites where the ZMapp antibodies bind have been unaffected so far.
The new research is part of the National Institutes of Health-funded Viral Hemorrhagic Fever Immunotherapeutic Consortium, which is testing antibodies from 25 laboratories around the world with the goal of developing the best cocktail for neutralizing Ebola virus and other closely related hemorrhagic fever viruses.
The next step for the consortium is to study the new antibodies from human survivors of the current outbreak. Saphire, who leads the consortium, hopes the group can also develop a back-up cocktail in case the virus mutates and becomes resistant to treatment.
ZMapp is expected to go into clinical trials in early 2015. The antibodies in the cocktail were originally isolated by the Public Health Agency of Canada and the U.S. Army Medical Research Institute of Infectious Disease.
In addition to Ward, Saphire and Murin, the authors of the paper “Structures of protective antibodies reveal sites of vulnerability on Ebola virus” were Marnie L. Fusco and Zachary A. Bornholdt of TSRI; Xiangguo Qiu of the Public Health Agency of Canada; Gene G. Olinger of the National Institutes of Health; Larry Zeitlin of Mapp Biopharmaceutical; and Gary P. Kobinger of the Public Health Agency of Canada and the University of Manitoba.
Funding for the research was provided by the National Institutes of Health (R01AI067927 and U19AI109762), the National Institute of General Medical Sciences (GM103310), the National Science Foundation, the Ray Thomas Edwards Foundation and the Burroughs Welcome Fund.
Source: Scripps Research Institute
Dear Helpdesk: Working in a Toxic Health Care Environment
March 28th 2024Dear Helpdesk is your steadfast companion, offering life coaching and workplace advice from 2 seasoned IPs for some of your most challenging real-life situations. Let us help you navigate the intersection between work and life, guiding you to navigate the dynamic world of infection prevention with confidence and grace. This article is on handling a toxic health care environment.
Product Locator: Spring and Early Mother's Day Gift Guide for Infection Prevention Personnel
March 27th 2024Whether it's a spring holiday, birthdays, or no reason at all, infection prevention personnel love to give and receive gifts that help at the end of a stressful day. Infection Control Today® offers some gift ideas for infection prevention personnel and their families.
Catching Up With Vangie Dennis, AORN 2022-2023 President at AORN 2024
March 26th 2024Infection Control Today (ICT) had the privilege of catching up with Vangie Dennis, MSN, RN, CNOR, CMLSO, at the Association of periOperative Registered Nurses' (AORN’s) International Surgical Conference & Expo 2024. As the former president of AORN and an esteemed figure in perioperative services, Vangie Dennis shared insights into her recent endeavors and the exciting new chapter she's embarked upon.
How To Optimize Your Time Management Strategies for the Busy Infection Preventionist
March 25th 2024Is your calendar resembling a chaotic masterpiece of overlapping tasks? Join the club of infection preventionists striving to balance responsibilities. Dive into proven strategies from a fellow infection preventionist to reclaim control of your time, streamline tasks, and boost productivity effectively. This is an IP Lifeline article.