Development of antibodies to eliminate tick-borne encephalitis virus by Nagasaki University and others

A research group led by Nagasaki University has successfully developed antibodies against the virus that causes "tick-borne encephalitis," which is primarily transmitted by ticks and has been reported in Hokkaido and other areas. The challenge had been that the brain has a filter-like mechanism called the blood-brain barrier (BBB) that prevents the entry of harmful substances, and drugs cannot pass through it. The antibodies developed through this research are fused with peptides and so can penetrate the BBB and eliminate the virus in the brain. These antibodies are expected to be applied to therapeutic drugs for tick-borne encephalitis.

Professor Kentaro Yoshii, who studies virology at the National Research Center for the Control and Prevention of Infectious Diseases at Nagasaki University, and his colleagues began their research at Hokkaido University, with which they were previously affiliated, to establish treatment methods for tick-borne encephalitis, for which there is no effective treatment. When the tick-borne encephalitis virus enters the human body, it reaches the brain and causes encephalitis. Treatment is only symptomatic, and because the brain does not regenerate, even if a person's life is saved, serious aftereffects such as paralysis remain.

The BBB in the brain exists between the brain and blood, and allows substances necessary for the brain such as glucose and insulin, as well as some viruses such as the Japanese encephalitis virus, to pass through. On the other hand, it has the property of not allowing therapeutic drugs to pass through, and it was difficult to find a method to successfully deliver them to the brain.

Yoshii's group was inspired by the existence of molecules that have the property of passing through the BBB and decided to use antibodies and their receptors. While normal antibodies alone cannot pass through cells, they thought that applying peptides consisting of linked amino acids that have the property of passing through the BBB might work, so they created an antibody that fused IgG antibodies with peptides. They used IgG antibodies because these antibodies have the property of gradually increasing after infection, so they thought this could serve as a drug that could be applied in the acute phase of infection.

When they investigated the movement of antibodies in mice using the "BBB-penetrating antibodies" developed through five years of research, they were able to confirm that the antibodies properly reached the brain. Furthermore, when they observed the viral load in mice with tick-borne encephalitis, they found that the group that received antibody injections had a significant reduction in viral load compared with the group that received no treatment, indicating that the antibodies were effective.

Yoshii discussed future prospects, saying, "I want to try attaching more types of antibodies," and added, "It is groundbreaking that we were able to prove that we can reduce the virus. However, to prevent tick-borne encephalitis, I want people to take preventive measures such as protecting their skin with clothing to avoid being bitten by ticks (during outdoor activities)."

The research was conducted with funding from the Grants-in-Aid for Scientific Research program of the Japan Society for the Promotion of Science and funding from the Japan Agency for Medical Research and Development (AMED). The results were published in the electronic version of the American Society for Microbiology journal mSphere on July 7.