Mab cures West Nile-infected mice
infected with the West Nile virus, which if confirmed, could become
one of the first monoclonal antibodies used as a treatment for an
infectious disease.
The latest development comes after 2004 in which the West Nile virus caused 2,470 infections and 88 deaths in the United States. The mosquito-borne virus, first isolated in Africa in 1937, spread to the Middle East, Europe, and Asia before arriving in the United States in 1999. Most infections with the virus are mild or symptom-free, but infections in people with weakened immune systems and those over 50 sometimes lead to serious complications or death.
Researchers from the Washington University School of Medicine discovered that in a certain strain of mice, which normally only has about a 10 per cent survival rate after West Nile infection, single doses of the antibodies given soon after infection could boost survival rates to 90 per cent or higher.
Scientists initially produced a panel of many West Nile virus antibodies from mouse cells. The human immune system would clear out these foreign antibodies quickly, so when they had identified a potent antibody, scientists at Macrogenics clipped out the genetic material that controls the antibody's targeting and cloned it into a human antibody. The "humanised" antibody should be less likely to induce an adverse human immune system response.
Antibodies typically work by attaching to a piece of a foreign cell or substance, which causes immune system cells known as macrophages to pick up the substance and clear it from the body.
"To our knowledge, these experiments are the first successful demonstration of the use of a humanised antibody as a post-exposure therapy against a viral disease," says senior investigator Michael Diamond, assistant professor of molecular microbiology, pathology and immunology and of medicine.
"They also suggest antibody-based therapeutics may have a broader utility against other infectious diseases," he added.
Diamond was quick to point out that Macrogenics the company that licensed the antibody from Washington University must complete preliminary studies before the antibody can be tested in humans.
"We could give a single dose of this antibody to mice as long as five days after infection, when West Nile virus had entered the brain, and it could still cure them," said Diamond.
"It also completely protected against death from the disease."
Other monoclonal antibodies are currently in development or use as anti-cancer and anti-inflammatory treatments. An antibody against respiratory syncytial virus (RSV) is approved for use as a prophylactic treatment in children at risk of the disease in hospitals. Unlike the West Nile virus antibody, though, the RSV antibody has to be given prior to infection.
West Nile virus belongs to a family of viruses known as flaviviruses, several of which are spread by mosquito bites. Other flaviviruses include the virus that causes dengue fever, a potentially life-threatening infection prevalent in tropical cities. Centres for Disease Control and Prevention epidemiologists estimate there are 100 million cases of dengue worldwide every year.
"A lot of what we're learning from the West Nile virus antibody will be of consequence for the development of a pediatric dengue vaccine," says co-author Daved Fremont, associate professor of biochemistry and molecular biophysics and of pathology and immunology.
"Currently there are no safe vaccines for dengue infections."
