Primary Human Neutrophils Exhibit a Unique HIV-Directed Antibody-Dependent Phagocytosis Profile—Powell 2019

RV144, the only HIV vaccine study to show efficacy, linked protection to antibodies (Abs) mediating function via the "constant" immunoglobulin region, the crystallizable fragment (Fc). These findings indicate immunizations that induce Abs by activating Fc receptors (FcRs) on appropriate leukocytes to fight viruses. >50% of leukocytes are neutrophils, which have distinct FcRs. We compared human neutrophil ADCP activity to THP-1 cells. HIV-specific Abs induced ADCP of HIV envelope-coated beads. Neutrophil donors have distinct ADCP profiles than THP-1 cells. mAb ELISA titers linked with THP-1 cell ADCP but not neutrophils. Primary monocytes tested mAbs. Donor-to-donor variance was high and impeded dataset processing, but it was an important finding. This study shows that FcR-mediated Ab activity with a commonly used cell line like THP-1 does not necessarily reflect relevant Ab functionality in vivo, and that HIV antibodies best suited to eliciting antiviral activities by primary cells should be studied in detail.

Powell, R. L. R., Fox, A., Itri, V., & Zolla-Pazner, S. (2019). Primary Human Neutrophils Exhibit a Unique HIV-Directed Antibody-Dependent Phagocytosis Profile. Journal of innate immunity, 11(2), 181–190. https://doi.org/10.1159/000494371