Development of a feline TNF-α monoclonal antibody with therapeutic potential against feline infectious peritonitis
| Project/Area Number |
22780285
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Clinical veterinary science
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| Research Institution | Kitasato University |
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Principal Investigator |
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| Project Period (FY) |
2010 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2011: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | TNF-a / コロナウイルス / 抗体療法 / 猫伝染性腹膜炎 / 治療 / TNF-α |
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| Research Abstract |
Feline infectious peritonitis virus (FIP virus: FIPV), a feline coronavirus (FCoV) of the family Coronaviridae, causes a fatal disease called FIP in wild and domestic cat species. We previously showed that virus replication in macrophages induced TNF-α production, and that the TNF-a produced was involved in aggravating the pathology of FIP: TNF-a produced by FIPV-infected macrophages was involved in lymphopenia and an increase in the level of the cellular receptor of type II FIPV, aminopeptidase N (APN). TNF-a reportedly inhibits neutrophil apoptosis, which suggestsits involvement in neutrophilia in cats with FIP. These findings suggest that FIP symptoms may also be alleviated by administering a feline TNF-a-neutralizing antibody to cats with FIP. However, no feline TNF-a-neutralizing antibody has been developed. We attempted to prepare feline TNF-a-recognizing monoclonal antibodies (anti-feline TNF-a MAbs) and investigated whether these MAbs inhibited feline TNF-a activities. Furthermore, we investigated the application of an anti-feline TNF-a MAb as a therapeutic drug for FIP in vitro. Anti-feline TNF-a MAb 2-4 (MAb 2-4) exhibited high neutralizing activity against natural TNF-a derived from FIPV-infected macrophages, and was confirmed to inhibit the following feline TNF-a-induced conditions in vitro. It was suggested that Mab 2-4 inhibited FIP pathology by neutralizing the physiological activities of TNF-a.
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Report
(4 results)
Research Products
(15 results)
