A Role for Fc-Mediated Humoral Immunity in Reducing HIV Transmission Rates between HIV Serodiscordant Heterosexual Couples☆

HIV serodiscordant couples are an extremely useful tool for examining immune responses that may contribute to reduced transmission or protection from HIV infection. A homozygous 32-base pair deletion in the gene encoding the Chemokine receptor 5 protein (CCR5) is strongly associated with protection from HIV infection (Huang et al., 1996). In contrast, the contribution of humoral, cellular and innate immunity in individuals who have been repeatedly exposed to HIV-1 but remain seronegative (ESN) protection has been more controversial, with several studies suggesting roles for T cells, neutralizing antibodies and innate immunity, including monocytes and NK cells (Lederman et al., 2010). Analysis of themoderately protective RV144 ‘Thai’ Phase III HIV vaccine trial suggests a role for Fc-mediated humoral immunity in protection and control of HIV infection (Chung et al., 2015; Haynes et al., 2012). However, few studies have examined ESN or serodiscordant couples for Fc-mediated effector responses. In this issue of EBioMedicine, Ruiz et al. (Ruiz et al., 2017) examined nine heterosexual serodiscordant couples to determine differences in cellular or humoral immune responses. ESN individuals did not induce any significant HIV-specific humoral immune responses, very weak HIV-specific cellular responses were observed in only two ESN, and modestly elevated levels of macrophage-derived chemokine levels were detected in plasma, although this difference lost statistical significance after correction for multiple comparisons. However, the authors report that the magnitude of antibody-dependent cellular cytotoxicity (ADCC) responses and gp120-specific IgG/IgA ratios were elevated within chronically infected HIV individuals who did not transmit HIV to their heterosexual ESN partners. This preliminary work suggests that ADCC magnitudemay contribute to reduced viral transmission. Interestingly both ADCC responses and IgG/IgA ratios correlated with increased CD4+ T cell counts, but not viral loads, in HIV individuals that did not transmit to their respective partners, while these associations were absent within chronically infected HIV transmitters. Whether