Fc-mediated effector function contributes to the in vivo antiviral effect of an HIV neutralizing antibody.

Proceedings of the National Academy of Sciences of the United States of America
Mangaiarkarasi AsokanRichard A Koup

Abstract

Treatment of HIV infection with either antiretroviral (ARV) therapy or neutralizing monoclonal antibodies (NAbs) leads to a reduction in HIV plasma virus. Both ARVs and NAbs prevent new rounds of viral infection, but NAbs may have the additional capacity to accelerate the loss of virus-infected cells through Fc gamma receptor (FcγR)-mediated effector functions, which should affect the kinetics of plasma-virus decline. Here, we formally test the role of effector function in vivo by comparing the rate and timing of plasma-virus clearance in response to a single-dose treatment with either unmodified NAb or those with either reduced or augmented Fc function. When infused into viremic simian HIV (SHIV)-infected rhesus macaques, there was a 21% difference in slope of plasma-virus decline between NAb and NAb with reduced Fc function. NAb engineered to increase FcγRIII binding and improve antibody-dependent cellular cytotoxicity (ADCC) in vitro resulted in arming of effector cells in vivo, yet led to viral-decay kinetics similar to NAbs with reduced Fc function. These studies show that the predominant mechanism of antiviral activity of HIV NAbs is through inhibition of viral entry, but that Fc function can contribute to the overall ant...Continue Reading

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Citations

Jul 18, 2020·Current Opinion in HIV and AIDS·Margaret C Carpenter, Margaret E Ackerman
Jan 12, 2021·Molecular Therapy. Methods & Clinical Development·James M TerminiRonald C Desrosiers
Mar 24, 2021·Expert Opinion on Therapeutic Targets·Simone I Richardson, Penny L Moore
Jun 30, 2021·Expert Review of Vaccines·Christopher P Karch, Gary R Matyas
Jun 15, 2021·Frontiers in Public Health·David A SpencerAnn J Hessell
Aug 7, 2021·Frontiers in Immunology·Stephen R Walsh, Michael S Seaman
Aug 28, 2021·International Journal of Molecular Sciences·Patricia GogeschMartina Anzaghe

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