Two studies recently published in the journal Science Translational Medicine, revealed a possible new vaccine treatment for JC virus with important implications for multiple sclerosis (MS) treatment. The studies are entitled “JC polyomavirus mutants escape antibody-mediated neutralization” and “Broadly neutralizing human monoclonal JC polyomavirus VP1–specific antibodies as candidate therapeutics for progressive multifocal leukoencephalopathy.” The research was led by an international team of scientists at the National Cancer Institute in the United States, San Raffaele Scientific Institute in Italy, and University Hospital Zurich, University of Zurich, and Neurimmune Holding AG in Switzerland.
The JC virus is usually not harmful, unless the infected person has a weakened immune system, as is the case of MS patients under immunosuppressive medications. In these cases, the JC virus can opportunistically infect the brain and induce a rare, often fatal brain disease called progressive multifocal leukoencephalopathy (PML), which is characterized by inflammation and progressive damage of the white matter of the brain.
“In healthy people, the disease never breaks out as the immune system keeps it well under control. Once the immune system is compromised, however, such as in patients with tumors, leukemia, AIDS, autoimmune diseases and certain immunosuppressive treatments, the JC virus is able to alter its genetic information and infect the brain,” explained the co-author of both studies Dr. Roland Martin from the University of Zurich in a news release.
One well-known case is the use of the humanized monoclonal antibody Tysabri (natalizumab) as a therapy for MS, which has been associated with the development of PML. It is thought that while the antibody prevents immune cells from reaching the brain, it also blocks its immunosurveillance system. It is estimated that more than 560 MS patients in the world have developed PML, and of these, 20% died from the disease, as there is no treatment available for JC virus infection.
Now, researchers report that there is a possible vaccination approach to preventing PML, or, if a person’s brain is already infected, a treatment with virus-specific human antibodies.
In one of the studies, researchers found that antibodies in PML patients are often unable to recognize the JC virus strain that has infected the individual due to viral genetic mutations that make the virus “invisible” to the host’s immune system. In the second study, authors offer a solution, as they show that the use of broadly neutralizing antibodies obtained from a particular PML patient who recovered from the disease can be an effective therapeutic strategy for PML and JC virus infection.
The discovery of these specific antibodies allowed the development of a vaccine based on the coating protein of the JC virus. Using mouse models and 3 PML patients, researchers showed that vaccination triggers a very strong antibody immune response — a response so effective that patients were able to eliminate the JC virus from their brains.
“We made a major breakthrough,” concluded Dr. Martin. “We managed to isolate antibody-producing cells from a patient who survived PML and use them to produce neutralizing antibodies against the JC virus. These human antibodies have a major advantage: they recognize the most important mutants of the JC virus that can cause PML. They now make promising candidates for the development of a treatment for PML.”
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