| Title: | In vitro and in vivo antivirus activity of an anti-programmed death-ligand 1 (PD-L1) rat-bovine chimeric antibody against bovine leukemia virus infection |
| Authors: | Nishimori, Asami Browse this author |
| Konnai, Satoru Browse this author →KAKEN DB |
| Okagawa, Tomohiro Browse this author |
| Maekawa, Naoya Browse this author |
| Ikebuchi, Ryoyo Browse this author |
| Goto, Shinya Browse this author |
| Sajiki, Yamato Browse this author |
| Suzuki, Yasuhiko Browse this author →KAKEN DB |
| Kohara, Junko Browse this author |
| Ogasawara, Satoshi Browse this author →KAKEN DB |
| Kato, Yukinari Browse this author |
| Murata, Shiro Browse this author →KAKEN DB |
| Ohashi, Kazuhiko Browse this author →KAKEN DB |
| Issue Date: | 26-Apr-2017 |
| Publisher: | PLOS |
| Journal Title: | PLoS One |
| Volume: | 12 |
| Issue: | 4 |
| Start Page: | e0174916 |
| Publisher DOI: | 10.1371/journal.pone.0174916 |
| Abstract: | Programmed death-1 (PD-1), an immunoinhibitory receptor on T cells, is known to be involved in immune evasion through its binding to PD-ligand 1 (PD-L1) in many chronic diseases. We previously found that PD-L1 expression was upregulated in cattle infected with bovine leukemia virus (BLV) and that an antibody that blocked the PD-1/PD-L1 interaction reactivated Tcell function in vitro. Therefore, this study assessed its antivirus activities in vivo. First, we inoculated the anti-bovine PD-L1 rat monoclonal antibody 4G12 into a BLV-infected cow. However, this did not induce T-cell proliferation or reduction of BLV provirus loads during the test period, and only bound to circulating IgM+ B cells until one week post-inoculation. We hypothesized that this lack of in vivo effects was due to its lower stability in cattle and so established an anti-PD-L1 rat-bovine chimeric antibody (Boch4G12). Boch4G12 was able to bind specifically with bovine PD-L1, interrupt the PD-1/PD-L1 interaction, and activate the immune response in both healthy and BLV-infected cattle in vitro. Therefore, we experimentally infected a healthy calf with BLV and inoculated it intravenously with 1 mg/kg of Boch4G12 once it reached the aleukemic (AL) stage. Cultivation of peripheral blood mononuclear cells (PBMCs) isolated from the tested calf indicated that the proliferation of CD4+ T cells was increased by Boch4G12 inoculation, while BLV provirus loads were significantly reduced, clearly demonstrating that this treatment induced antivirus activities. Therefore, further studies using a large number of animals are required to support its efficacy for clinical application. |
| Rights: | http://creativecommons.org/licenses/by/4.0/ |
| Type: | article |
| URI: | http://hdl.handle.net/2115/68485 |
| Appears in Collections: | 国際連携研究教育局 : GI-CoRE (Global Institution for Collaborative Research and Education : GI-CoRE) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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