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.

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 T-cell 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.

• Authors: Asami Nishimori, Satoru Konnai, Tomohiro Okagawa, Naoya Maekawa, Ryoyo Ikebuchi, Shinya Goto, Yamato Sajiki, Yasuhiko Suzuki, Junko Kohara, Satoshi Ogasawara, Yukinari Kato, Shiro Murata, Kazuhiko Ohashi
• Journal: PloS one (PLoS One) Vol. 12 Issue 4 Pg. e0174916 ( 2017) ISSN: 1932-6203 [Electronic] United States
• PMID: 28445479 (Publication Type: Journal Article)

Chemical References

• Antibodies, Monoclonal
• Antiviral Agents
• B7-H1 Antigen
• Recombinant Fusion Proteins
• Viral Proteins
• Interferon-gamma

Topics

• Animals
• Antibodies, Monoclonal (genetics, immunology, pharmacology, therapeutic use)
• Antigen-Antibody Reactions
• Antiviral Agents (therapeutic use)
• B-Lymphocytes (immunology, metabolism)
• B7-H1 Antigen (immunology)
• CD4-Positive T-Lymphocytes (cytology, immunology, metabolism)
• Cattle
• Cells, Cultured
• Enzootic Bovine Leukosis (drug therapy, prevention & control, virology)
• Interferon-gamma
• Leukemia Virus, Bovine (metabolism, physiology)
• Leukocytes, Mononuclear (cytology, drug effects, metabolism)
• Lymphocyte Activation (drug effects)
• Rats
• Recombinant Fusion Proteins (biosynthesis, isolation & purification, pharmacology)
• Viral Load
• Viral Proteins (immunology)