Despite the wide availability of antiretroviral drugs, more than 250,000 infants are vertically infected with HIV-1 annually, emphasizing the need for additional interventions to eliminate pediatric HIV-1 infections. Here, we aimed to define humoral immune correlates of risk of mother-to-child transmission (MTCT) of HIV-1, including responses associated with protection in the RV144 vaccine trial. Eighty-three untreated, HIV-1-transmitting mothers and 165 propensity score-matched nontransmitting mothers were selected from the Women and Infants Transmission Study (WITS) of US nonbreastfeeding, HIV-1-infected mothers. In a multivariable logistic regression model, the magnitude of the maternal IgG responses specific for the third variable loop (V3) of the HIV-1 envelope was predictive of a reduced risk of MTCT. Neutralizing Ab responses against easy-to-neutralize (tier 1) HIV-1 strains also predicted a reduced risk of peripartum transmission in secondary analyses. Moreover, recombinant maternal V3-specific IgG mAbs mediated neutralization of autologous HIV-1 isolates. Thus, common V3-specific Ab responses in maternal plasma predicted a reduced risk of MTCT and mediated autologous virus neutralization, suggesting that boosting these maternal Ab responses may further reduce HIV-1 MTCT.
Maternal HIV-1 envelope-specific antibody responses and reduced risk of perinatal transmission
Permar, S. R., Fong, Y., Vandergrift, N., Fouda, G. G., Gilbert, P., Parks, R., Jaeger, F. H., Pollara, J., Martelli, A., Liebl, B. E., Lloyd, K., Yates, N. L., Overman, R. G., Shen, X., Whitaker, K., Chen, H., Pritchett, J., Solomon, E., Friberg, E., ... Haynes, B. F. (2015). Maternal HIV-1 envelope-specific antibody responses and reduced risk of perinatal transmission. Journal of Clinical Investigation, 125(7), 2702-2706. https://doi.org/10.1172/JCI81593