WASHINGTON, July 2 (Xinhua) -- 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 research findings appear in the July 3 issue of
the Proceedings of the National Academy of Sciences. The team was led by Dimiter
Dimitrov of the National Cancer Institute.
When the first SARS outbreak occurred in 2002,
Dimitrov responded to the public health crisis by applying his laboratory's
expertise on 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 glycoprotein, the part of the virus that binds and allows entry into human
cells, provided the knowledge needed to identify two human antibodies against
the SARS virus.
The two antibodies can 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 taken
from a library of human antibodies the researchers developed from the blood of
10 healthy volunteers.
When tested in cells in the laboratory, both
antibodies potently neutralized samples of the virus from both outbreaks in
2002-2003 and 2003-2004. 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 mice.
Mice were given an injection of one of the two antibodies, and 24 hours later
were exposed either to samples of the SARS virus from one of the two outbreaks
or to a virus isolated from civets.
Mice that received m396 or S230.15 were fully
protected from infection by SARS from humans, the researchers found. As with 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.
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 also be used for diagnosis and
research in the development of vaccines and inhibitors," summarized the
authors.