Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Human antibodies that block human and animal SARS viruses identified

04.07.2007
An international team of investigators has identified the first human antibodies that can neutralize different strains of the virus responsible for outbreaks of severe acute respiratory syndrome (SARS).

The researchers used a mouse model and in vitro assays (lab tests) to test the neutralizing activity of the antibodies. The research team was led by scientists from the National Cancer Institute (NCI) and the National Institute of Allergy and Infectious Diseases (NIAID), both parts of the National Institutes of Health, and included collaborators from the U.S. Army (USAMRIID), academic institutions in the United States, Switzerland, and Australia. The research findings appear after the July 2, 2007, early online edition of the Proceedings of the National Academy of Sciences.

SARS outbreaks occurred in humans in 2002-2003 and again in 2003-2004, and each outbreak was thought to have occurred when the virus jumped from an animal host to humans. Therefore, it appears that animal strains of the virus may be capable of triggering a future human outbreak.

“This study is important because the viral strain that caused the outbreak in people in 2002 probably no longer exists in nature,” explains Kanta Subbarao, M.D., NIAID, whose laboratory verified the efficacy of the anti-SARS antibodies in animal models. “What we need to prove for any vaccine, therapeutic, antibody, or drug is that it is effective not only against the strain of SARS virus isolated from people, but also against a variety of animal strains, because animals will be a likely source for re-emergence of the SARS virus.”

... more about:
»Antibodies »RBD »SARS »m396 »neutralize »strain »therapeutic

The research team was led by Dimiter S. Dimitrov, Ph.D., head of the Protein Interaction Group at NCI’s Frederick, Md., campus. When the first SARS outbreak occurred in 2002, Dimitrov responded to the public health crisis by applying his laboratory’s expertise in how viruses enter cells, which was gained in the study of HIV, to understand how this new virus enters and exploits human cells. Their research into the spike glycoprotein, the part of the virus that binds and allows entry into human cells, provided the knowledge needed to identify several human antibodies against the SARS virus.

“Our researchers at NCI Frederick have an extraordinary breadth of expertise, ranging far beyond cancer to areas such as AIDS research, advanced biotechnology, and vaccine manufacturing,” said NCI Director John E. Niederhuber, M.D. “We are realizing, as never before, that cancer is a model for many diseases, and NCI's research is a rich resource to our NIH colleagues and the biomedical research community at large.”

Dimitrov and his colleagues identified two human antibodies that bind to a region on the SARS virus’ spike glycoprotein that is called the receptor binding domain (RBD). One of the antibodies, called S230.15, was found in the blood of a patient who had been infected with SARS and later recovered. The second antibody, m396, was taken from a library of human antibodies the researchers developed from the blood of 10 healthy volunteers. Because humans already have immune cells that express antibodies that are very close to those that can effectively neutralize the SARS virus, m396 could be fished out from healthy volunteers. Dimitrov’s team next determined the structure of m396 and its complex with the SARS RBD and showed that the antibody binds to the region on the RBD that allows the virus to attach to host cells.

If the antibodies were successful in binding to the SARS RBD, they would prevent the virus from attaching to the SARS coronavirus receptor, ACE2, on the outside of human cells, effectively neutralizing it. When tested in cells in the laboratory, both antibodies potently neutralized samples of the virus from both outbreaks. The antibodies also neutralized samples of the virus taken from wild civets (a cat-like mammal in which strains of the virus were found during the outbreaks), though with somewhat lower potency.

The investigators next tested the antibodies in a mouse model of SARS virus infection. Mice were given an injection of one of the two antibodies, and then were exposed 24 hours later either to samples of the SARS virus from one of the two outbreaks or to virus isolated from civets. Mice that received m396 or S230.15 were fully protected from infection by SARS from humans, the researchers found. Similar to the experiments in cells in the laboratory, mice that received either antibody were also protected against infection by SARS from civets, though not completely.

Further analysis of the structure of m396 and its interactions with experimental mutations in the SARS virus receptor binding area suggested that the antibody can successfully neutralize all known forms of the virus. “This antibody neutralizes all strains of SARS we tested and is likely to neutralize all strains of the virus with known sequences,” said Dimitrov. “There are no other reports for such antibodies available.”

“This elegant research leaves us better prepared for the possible re-emergence in people of viruses similar to those that caused more than 8,000 documented SARS cases and nearly 800 deaths in 2002-2003,” noted NIAID Director Anthony S. Fauci, M.D. “This work, which could help inform the development of therapeutics, vaccines, and diagnostics, is a pre-emptive strike against a pathogen with the potential to re-emerge.”

The discovery of two effective antibodies has the advantage that a newly emergent variation of the SARS coronavirus might be insensitive to neutralization with one, but still susceptible to the other. “Our results demonstrate novel potential antibody-based therapeutics against SARS that could be used alone or in combination...these human antibodies could be also used for diagnosis and as research reagents in the development of vaccines and inhibitors,” summarized the authors.

NCI Press Officers | EurekAlert!
Further information:
http://www.nih.gov
http://www3.niaid.nih.gov
http://www.cancer.gov

Further reports about: Antibodies RBD SARS m396 neutralize strain therapeutic

More articles from Life Sciences:

nachricht The balancing act: An enzyme that links endocytosis to membrane recycling
07.12.2016 | National Centre for Biological Sciences

nachricht Transforming plant cells from generalists to specialists
07.12.2016 | Duke University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

NTU scientists build new ultrasound device using 3-D printing technology

07.12.2016 | Health and Medicine

The balancing act: An enzyme that links endocytosis to membrane recycling

07.12.2016 | Life Sciences

How to turn white fat brown

07.12.2016 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>