Therapy with CTLA4-Ig and an antiviral monoclonal antibody controls chikungunya virus arthritis

In 2013, chikungunya virus (CHIKV) transmission was documented in the Western Hemisphere, and the virus has since spread throughout the Americas with more than 1.8 million people infected in more than 40 countries. CHIKV targets the joints, resulting in symmetric polyarthritis that clinically mimics...

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Bibliographic Details
Published in:Science translational medicine 2017-02, Vol.9 (375)
Main Authors: Miner, Jonathan J, Cook, Lindsey E, Hong, Jun P, Smith, Amber M, Richner, Justin M, Shimak, Raeann M, Young, Alissa R, Monte, Kristen, Poddar, Subhajit, Crowe, Jr, James E, Lenschow, Deborah J, Diamond, Michael S
Format: Article
Language:English
Subjects:
Abatacept - therapeutic use
Animals
Antibodies, Neutralizing - therapeutic use
Antibodies, Viral - therapeutic use
Antiviral Agents - therapeutic use
Arthritis, Infectious - drug therapy
Arthritis, Infectious - virology
Chemokines - immunology
Chikungunya Fever - drug therapy
Chikungunya virus
Cytokines - immunology
Leukocytes - immunology
Mice
Mice, Inbred C57BL
Viral Load
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Summary:In 2013, chikungunya virus (CHIKV) transmission was documented in the Western Hemisphere, and the virus has since spread throughout the Americas with more than 1.8 million people infected in more than 40 countries. CHIKV targets the joints, resulting in symmetric polyarthritis that clinically mimics rheumatoid arthritis and can endure for months to years. At present, no approved treatment is effective in preventing or controlling CHIKV infection or disease. We treated mice with eight different disease-modifying antirheumatic drugs and identified CLTA4-Ig (abatacept) and tofacitinib as candidate therapies based on their ability to decrease acute joint swelling. CTLA4-Ig reduced T cell accumulation in the joints of infected animals without affecting viral infection. Whereas monotherapy with CTLA4-Ig or a neutralizing anti-CHIKV human monoclonal antibody provided partial clinical improvement, therapy with both abolished swelling and markedly reduced levels of chemokines, proinflammatory cytokines, and infiltrating leukocytes. Thus, combination CTLA4-Ig and antiviral antibody therapy controls acute CHIKV infection and arthritis and may be a candidate for testing in humans.
ISSN:1946-6234
1946-6242
DOI:10.1126/scitranslmed.aah3438