Professor Yasuko Mori led a research group that succeeded in the humanization of mouse antibodies. These antibodies can neutralize infections caused by the human herpesvirus 6B (HHV-6B). Infections by HHV-6B in infants lead to complications like encephalitis. This refers to brain inflammation. An effective way to deal with the infection is yet to be found.
The research team created the humanized antibodies on the basis of the mouse antibodies for HHV-6B. The Journal of Virology published their findings on March 6th. They also introduced the findings in the HHV-6 Foundation Newsletter.
Almost all children between ages 6 and 18 months become infected with HHV-6B. The initial infection leads to rash and sudden-onset fever. This condition has a favorable prognosis although almost 150 cases result in encephalitis annually. Almost half of these patients end up with neurological complications. HHV-6B stays latent in our body after the initial infection. It can reactivate whenever our immune system weakens. This is bad for patients who have had to receive stem cell transplants. They may experience frequent life-threatening encephalitis after the transplant.
How they did it?
The team had identified the protein complex gH/gL/gQ1/gQ2 to be an important factor for the HHV-6B infection. They also identified the human cellular receptor CD134 (OX40) which expresses on stimulated T-cells, normally targets of the infection. Previous studies showed that interactions between the receptor and the protein complex were the key to infection.
They created monoclonal antibodies from mice. This showed that the antibodies blocking activities of the gH/gL/gQ1/gQ2 complex could be used to regulate HHV-6B infection. The team plans to develop a clinically applicable treatment that can deal with the HHV-6B gH/gL/gQ1/gQ2 complex.
However, the mice’s antibodies are targeted by the human immune system. They are destroyed once they enter our body. This means that further alterations are necessary so as to suppress the immune reaction in our body before their use in a clinical setting. The team tested humanization of the mouse antibodies with the use of gene-altering technology.
In the study, the team changed two kinds of mouse IgG antibodies in order to target gH and gQ1 in HHV-6B gH/gL/gQ1/gQ2 complex. They started by analyzing the mouse’s antibodies DNA sequence making chimeric human-mouse genes. To purify the chimeric antibodies produced. They introduced the gene to cell cultures. They confirmed that the antibodies maintained effectiveness against HHV-6B gH/gL/gQ1/gQ2 complex. They carried out more quantitative analysis and verified that chimera antibodies could block HHV-6B infection just as the mouse antibodies.
The research was successful in creating artificial antibodies, proving their effectiveness against HHV-6B and triggered a lower response from the immune system. The antibodies still contain parts originating from mice. The next step should be to replace the mice parts with human antibodies. This is so to create antibodies suitable for clinical use.
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Science Daily. (2019, 04 26). Retrieved 05 04, 2019, from www.sciencedaily.com: https://www.sciencedaily.com/releases/2019/04/190426100337.htm