A team led by Professor Yasuko Mori (Department of Clinical Virology, Faculty of Infectious Diseases, Kobe University) successfully humanized mouse monoclonal antibody that neutralize infections caused by human herpesvirus 6B (HHV-6B) . Infection with HHV-6B in infants can lead to complications such as encephalitis (encephalitis), but no effective method for controlling infection has been found.
Professor Mori's team created "humanized" antibodies based on mouse (mouse) antibodies to HHV-6B. The study was published online March 6 in the journal Virology and is also available in the HHV-6 Foundation newsletter.
Almost every child from 6 to 18 months is infected with HHV-6B. The initial infection caused a sudden fever and rash. The condition has a good prognosis, but about 150 cases each year cause encephalitis, and about half of them have neurological complications. HHV-6B still lurks in our body after the initial infection and can be reactivated when our immune system has low defenses. This can be particularly bad for patients undergoing stem cell transplantation, who can experience frequent and life-threatening encephalitis after transplantation.
Professor Mori's research team has determined that the protein complex gH / gL / gQ1 / gQ2 is an essential factor for HHV-6B infection, and the human cell receptor CD134 (OX40) expresses a target of T cells stimulated by infection. In their previous studies, they showed that the interaction between this protein complex and the receptor is the key to infection. By producing monoclonal antibodies are produced by mice, they showed that antibodies that block the activity of the gH / gL / gQ1 / gQ2 complex can be used to modulate HHV-6B infection. The team's next goal is to develop clinically applicable treatments that can address the HHV-6B gH / gL / gQ1 / gQ2 complex.
However, antibodies from mice are targeted by the human immune system and are destroyed as they enter our body, so further changes are needed to suppress our immune response before they can be used in a clinical setting. Using genetic modification techniques, the team tested the humanization of mouse antibodies by creating a chimeric antibody by replacing the mouse antibody with a human antibody production in a constant domain, leaving only the variable domain directly acting on the HHV- Part of 6B.
In this study, the team changed two types of mouse IgG antibodies to target gH and gQ1 in the HHV-6B gH / gL / gQ1 / gQ2 complex. First, they analyzed the DNA sequence of mouse antibodies and made chimeric human-mouse genes. They purified the chimeric antibodies produced by introducing the gene into cell cultures and confirmed that the antibodies retained their effectiveness against the HHV-6B gH / gL / gQ1 / gQ2 complex. By performing further quantitative analysis, they confirmed that the chimeric antibody was able to block the infection of HHV-6B with the same potency as the mouse antibody.
This study successfully created artificial antibodies that are effective against HHV-6B and trigger a lower response to the human immune system. These antibodies still contain portions from the mouse, so the next step is to replace these portions with human antibodies to produce antibodies suitable for clinical use. HHV-6B only infects humans, which means there is no animal model of infection, and it is difficult to assess the effectiveness of these antibodies in vivo. In the future, if animal models can be used for testing, we hope these results will help create antibody-based therapies for HHV-6B infection.
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