Pre-Existing Infant Antibody-Dependent Cellular Cytotoxicity Associates with Reduced HIV-1 Acquisition and Lower Morbidity

SummaryIn humans, pre-existing anti-HIV-1 neutralizing antibodies (nAbs) have not been associated with decreased HIV-1 acquisition. We evaluated antibody-dependent cellular cytotoxicity (ADCC) present in pre-transmission infant and maternal plasma and breast milk (BM) against the contemporaneous maternal HIV-1 variants. HIV-1 exposed uninfected as compared to HIV-1 exposed infected infants had higher ADCC and a combination of ADCC and nAb responses against their corresponding mother’s strains. ADCC did not correlate with nAbs suggesting they are independent activities. The infected infants with high as compared to low ADCC, but not those with higher ADCC plus nAbs, had lower morbidity and mortality up to 1 year after birth. ADCC was lower in BM supernatants as compared to BM isolated IgG, but was not significantly different in the transmitting versus non-transmitting mothers’ BM or plasma. A high IgA to IgG ratio, as in BM supernatants, was also more prevalent in the infected infants, and it was also associated with lower infant ADCC. Overall, ADCC, more so than nAbs, against the exposure strains associates with lower mother-to-child-transmission (MTCT) and decreased post-infection infant morbidity. Future strategies should aim to elicit robust ADCC activity to prevent MTCT and to improve infant outcomes.