| RRC ID |
72829
|
| 著者 |
Wang B, Nishimura M, Maekawa Y, Kotari T, Okuno T, Mori Y.
|
| タイトル |
Humanization of Murine Neutralizing Antibodies against Human Herpesvirus 6B.
|
| ジャーナル |
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.
|
| 巻・号 |
93(10)
|
| 公開日 |
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
|
| リソース情報 |
| 研究用ヒト臍帯血幹細胞 |
|
