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.