RRC ID 72829
Author Wang B, Nishimura M, Maekawa Y, Kotari T, Okuno T, Mori Y.
Title Humanization of Murine Neutralizing Antibodies against Human Herpesvirus 6B.
Journal J Virol
Abstract Exanthem subitum is a common childhood illness caused by primary infection with human herpesvirus 6B (HHV-6B). It is occasionally complicated by febrile seizures and even encephalitis. 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 HHV-6B envelope glycoprotein complex gH/gL/gQ1/gQ2 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. In this study, we constructed chimeric forms of two neutralizing MAbs against HHV-6B to make humanized antibodies. Both showed neutralizing activities equivalent to those of their original forms. 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 cause of considerable mortality in patients, without any established treatments to date. The humanization of the murine neutralizing antibodies described in this research provided a feasible way to reduce the inherent immunogenicity of the antibodies without changing their neutralizing activities. These newly designed chimeric antibodies against HHV-6B have the potential to be candidates for antivirals for future use.
Volume 93(10)
Published 2019-5-15
DOI 10.1128/JVI.02270-18
PII JVI.02270-18
PMID 30842329
PMC PMC6498045
MeSH Animals Antibodies, Monoclonal Antibodies, Monoclonal, Humanized / metabolism Antibodies, Monoclonal, Humanized / pharmacology Antibodies, Neutralizing / immunology* Antiviral Agents Cell Line Genetic Engineering / methods HEK293 Cells Herpesvirus 6, Human / genetics Herpesvirus 6, Human / immunology* Humans Mice Viral Envelope Proteins / immunology
IF 4.501
Cord blood stem cells for research