Humanization of the murine neutralizing antibodies against human herpesvirus 6B.

Exanthem subitum is a common childhood illness caused by Human herpesvirus 6B (HHV-6B) primary infection. It is occasionally complicated by febrile seizure and even encephalitis. The HHV-6B reactivation also causes encephalitis especially after allogeneic hematopoietic stem cell transplantation. However, no adequate antiviral treatment for HHV-6B has yet been established. Mouse-derived monoclonal antibodies (Mabs) against the envelope glycoprotein complex gH/gL/gQ1/gQ2 of HHV-6B have been shown to neutralize the viral infection. These antibodies have the potential to become antiviral agents against HHV-6B despite their inherent immunogenicity to the human immune system. Humanization of Mabs derived from other species is one of the proven solutions to such a dilemma. Here, we constructed chimeric forms of two neutralizing Mabs against HHV-6B to make humanized antibodies. Both showed neutralizing activities equivalent to those in their original ones. This is the first report of humanized antibodies against HHV-6B and provides a basis for the further development of HHV-6B-specific antivirals. Importance Human herpesvirus 6B (HHV-6B) establishes lifelong latent infection in most individuals after the primary infection. Encephalitis is the most severe complication caused by both the primary infection and the reactivation of HHV-6B, and is the considerable cause of mortality in patients without any established treatments now. Humanization of the murine neutralizing antibodies described in this research provided a feasible way to reduce the inherent immunogenicity without changing the neutralizing activities. These newly designed chimeric antibodies against HHV-6B have the potential to be candidates of antiviral for future use.