Research ArticleANTIBODIES

Optimal therapeutic activity of monoclonal antibodies against chikungunya virus requires Fc-FcγR interaction on monocytes

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Science Immunology  22 Feb 2019:
Vol. 4, Issue 32, eaav5062
DOI: 10.1126/sciimmunol.aav5062

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Engaging monocytes to battle chikungunya

Antibody-binding receptors, including Fc receptors and complement receptors, play a central role in mediating antibody-dependent immune activation. Here, Fox et al. have examined the role of Fcγ receptors and complement component 1q (C1q) in meditating the therapeutic effects of monoclonal IgG antibodies targeting chikungunya virus. Using antibody engineering in conjunction with mouse strains lacking C1q or Fcγ receptors, they report that the therapeutic effects of these antibodies are dependent on expression of Fcγ receptors. Furthermore, by depleting distinct immune cell types, they found that engagement of Fc receptors on monocytes is central in driving antibody-dependent clearance of chikungunya virus.

Abstract

Chikungunya virus (CHIKV) is an emerging mosquito-borne virus that has caused explosive outbreaks worldwide. Although neutralizing monoclonal antibodies (mAbs) against CHIKV inhibit infection in animals, the contribution of Fc effector functions to protection remains unknown. Here, we evaluated the activity of therapeutic mAbs that had or lacked the ability to engage complement and Fcγ receptors (FcγR). When administered as post-exposure therapy in mice, the Fc effector functions of mAbs promoted virus clearance from infected cells and reduced joint swelling—results that were corroborated in antibody-treated transgenic animals lacking activating FcγR. The control of CHIKV infection by antibody-FcγR engagement was associated with an accelerated influx of monocytes. A series of immune cell depletions revealed that therapeutic mAbs required monocytes for efficient clearance of CHIKV infection. Overall, our study suggests that in mice, FcγR expression on monocytes is required for optimal therapeutic activity of antibodies against CHIKV and likely other related viruses.

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