論文 - 詳細
| 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 |
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オルトメトリクス指標項目
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| 最多言及媒体 | News |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 研究用ヒト臍帯血幹細胞 | |