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Antibodies Isolated for Chikungunya Virus

James Crowe in the lab

James Crowe (Susan Urmy, Vanderbilt University)

9 July 2015. Researchers at Vanderbilt University in Nashville isolated 13 antibodies from a person infected with the chikungunya virus shown to possibly prevent and treat infections in lab mice. The team led by James Crowe, director of Vanderbilt’s Vaccine Center, published its findings yesterday in the journal Cell Host & Microbe.

Chikungunya is a disease caused by viruses carried by mosquitoes that results in symptoms similar to arthritis, such joint pain and swelling, but also fever, headache, muscle pain, and rash that can persist for months or years. Before 2013, chikungunya occurred in Africa, Asia, Europe and islands in the Pacific and Indian oceans. Beginning in 2013, however, cases of the disease were reported in the Caribbean, and has since spread to countries in South and North America, including the U.S.

Centers for Disease Control and Prevention says in 2014 some 2,800 cases of chikungunya were reported in the U.S., and about 4,700 cases in U.S. territories. There are no treatments or vaccines to prevent getting chikungunya.

Crowe and colleagues isolated the highly specific antibodies, called monoclonal antibodies, from an individual who got the virus in Sri Lanka in 2006. Their process uses 1 to 2 ounces of blood, separating the red and white blood cells. Among the white blood cells are B cells that the immune system uses to produce antibodies. Although the individual contracted the disease more than 5 years earlier, chikungunya antibodies were still in the person’s blood.

The researchers used a technique to produce 30 hybridomas, hybrid cells containing human antibodies that react to antigens injected and produced in mice. The team sequenced the gene regions of the hybridomas containing the antibodies to discover the genomic make-up of the genes that send virus-fighting signals to the infection. Those antibody genes were then cloned and reproduced in the lab to produce engineered monoclonal antibodies.

The team tested the monoclonal antibodies in lab cultures for their ability to bind to a protein known as E2 expressed on the surface of the viruses and neutralize them. The tests show 13 of antibodies had what the authors called ultrapotency when tested with live chikungunya viruses.

The researchers tested the monoclonal antibodies, both the ultrapotent and others, in lab mice infected with chikungunya for their ability to prevent and treat the disease. In the first round, one group of mice received the antibodies before a lethal injection of chikungunya virus. Mice receiving the ultrapotent antibodies were protected against the virus, while those receiving the weaker antibodies had lower and varying survival rates. A control group that did not receive any antibodies died within 4 days.

The team also tested the monoclonal antibodies in mice as a therapy for chikungunya after exposure to the disease. They found the antibodies provide a varying degree of protection 48 hours after infection from the virus, while 2 of the antibodies protected more than half of the lab mice for as long as 60 hours after infection.

Crowe and colleagues hope to test their antibodies in humans in about a year, after which they can be turned over to industry for clinical development and commercialization. “I wish we had the drug ready to test in humans now,” says Crowe in a university statement, “but you need to be careful and prepare these materials correctly. It takes a long time to manufacture and test and prove that materials are safe for humans.”

Crowe tells more about the research in the following video.

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