NIH Research Matters
July 9, 2007
Human Antibodies Block Human and Animal SARS Viruses
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 discovery could lead to new diagnostic tests and treatments for SARS.
SARS outbreaks in 2002-2003 and 2003-2004 are thought to have started when the virus jumped from an animal host to humans. Any future vaccine or therapeutic, therefore, needs to be effective against a variety of SARS strains that could jump between species at any time.
When the first SARS outbreak occurred in 2002, Dr. Dimiter S. Dimitrov of NIH's National Cancer Institute (NCI) responded to the public health crisis by applying his laboratory's expertise, gained in the study of HIV, to understand how this new virus enters and exploits human cells. His team's research into the spike glycoprotein, the part of the virus that binds to and allows it to enter human cells, provided the knowledge needed to move to the next step and start investigating methods of neutralizing the SARS virus. In this new study, Dimitrov led a team of scientists from NCI, NIH's National Institute of Allergy and Infectious Diseases (NIAID), the U.S. Army and academic institutions in the U.S., Switzerland and Australia.
As they explain this week in the early online edition of the Proceedings of the National Academy of Sciences, the researchers identified two human antibodies that bind to a region on the SARS virus' spike glycoprotein 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 found in a library of human antibodies developed from the blood of 10 healthy volunteers.
Both antibodies, the researchers found, prevented samples of the viruses from the SARS outbreaks from infecting human cells in the laboratory. The antibodies were also able to neutralize SARS virus samples taken from wild civets—cat-like mammals in which strains of the virus were found during the outbreaks.
The investigators next tested the antibodies in mice. Mice were injected with antibodies and exposed 24 hours later either to samples from one of the SARS outbreaks or to the civet virus. Mice that received m396 or S230.15 were fully protected from infection by SARS from humans. The antibodies also protected against infection by SARS from civets, though higher levels of antibody were needed.
The researchers showed that m396 binds to the region on the RBD that allows the virus to attach to host cells. Further analysis of the structure of m396 and its interactions with the SARS virus suggest that the antibody could successfully neutralize all forms of the virus with known sequences. Dimitrov said, "There are no other reports for such antibodies available."
This research may one day lead to the development of antibody-based therapeutics against SARS. It also paves the way for better diagnostic tools, vaccines and drugs to inhibit the virus.
- Severe Acute Respiratory Syndrome (SARS):
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