TY - JOUR
T1 - In vitro and in vivo antivirus activity of an antiprogrammed death-ligand 1 (PD-L1) ratbovine chimeric antibody against bovine leukemia virus infection
AU - Nishimori, Asami
AU - Konnai, Satoru
AU - Okagawa, Tomohiro
AU - Maekawa, Naoya
AU - Ikebuchi, Ryoyo
AU - Goto, Shinya
AU - Sajiki, Yamato
AU - Suzuki, Yasuhiko
AU - Kohara, Junko
AU - Ogasawara, Satoshi
AU - Kato, Yukinari
AU - Murata, Shiro
AU - Ohashi, Kazuhiko
N1 - Funding Information:
This research was supported by JSPS KAKENHI, grants from the Science and Technology Research Promotion Program for Agriculture, Forestry, Fisheries and Food Industry, Japan (grant 26058B to S.K.) and the NARO, Bio-oriented Technology Research Advancement Institution (the special scheme project on regional developing strategy: grant 16817557 to S.K.). This work was also supported in part by the Platform for Drug Discovery, Informatics, and Structural Life Science (PDIS) from Japan Agency for Medical Research and development, AMED (to Y.K.). The authors, Nishimori, Konnai, Okagawa, Maekawa, Suzuki, Murata and Ohashi, have a pending patent derived from this work (Tokugan 2016-159089). This does not alter our adherence to all PLOS ONE policies on sharing data and materials.
Publisher Copyright:
© 2017 Nishimori et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2017/4
Y1 - 2017/4
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pone.0174916
DO - 10.1371/journal.pone.0174916
M3 - Article
C2 - 28445479
AN - SCOPUS:85018351182
VL - 12
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 4
M1 - e0174916
ER -