Improved HIV-positive infant survival is correlated with high levels of HIV-specific ADCC activity in multiple cohorts

Defining immune responses that protect humans against diverse HIV strains has been elusive. Studying correlates of protection from mother-to-child transmission provides a benchmark for HIV vaccine protection because passively transferred HIV antibodies are present during infant exposure to HIV through breast milk. A previous study by our group illustrated that passively acquired antibody-dependent cellular cytotoxicity (ADCC) activity is associated with improved infant survival whereas neutralization is not. Here, we show, in another cohort and with two effector measures, that passively acquired ADCC antibodies correlate with infant survival. In combined analyses of data from both cohorts, there are highly statistically significant associations between higher infant survival and passively acquired ADCC levels (p = 0.029) as well as dimeric FcγRIIa (p = 0.002) or dimeric FcγRIIIa binding (p < 0.001). These results suggest that natural killer (NK) cell- and monocyte antibody-mediated effector functions may contribute to the observed survival benefit and support a role of pre-existing ADCC-mediating antibodies in clinical outcome. [Display omitted] ADCC activity is associated with improved survival of HIV-infected infantsBinding to dimeric forms of Fcγ receptors is also associated with survivalThese data support a role of ADCC in improved clinical outcome in infected infants Mother-to-child transmission is a unique setting to define correlates of protection from HIV pathogenesis. Yaffe et al. show that passively acquired ADCC, measured by two assays, correlates with improved survival of HIV-infected infants in two breastfeeding cohorts. These results suggest that pre-existing, ADCC-mediating antibodies contribute to improved HIV-positive infant clinical outcome.