Maternal HIV-1 envelope-specific antibody responses and reduced risk of perinatal transmission.
(Clinical Trial;Journal Article)
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.
Alam, S. Munir
Denny, Thomas Norton
Haynes, Barton Ford
Montefiori, David Charles
Moody, Michael Anthony
Pollara, Justin Joseph
Tomaras, Georgia Doris
Permar, SR; Fong, Y; Vandergrift, N; Fouda, GG; Gilbert, P; Parks, R; Jaeger, FH; Pollara, J; Martelli, A; Liebl, BE; Lloyd, K; Yates, NL; Overman, RG; Shen, X; Whitaker, K; Chen, H; Pritchett, J; Solomon, E; Friberg, E; Marshall, DJ; Whitesides, JF; Gurley, TC; Von Holle, T; Martinez, DR; Cai, F; Kumar, A; Xia, S-M; Lu, X; Louzao, R; Wilkes, S; Datta, S; Sarzotti-Kelsoe, M; Liao, H-X; Ferrari, G; Alam, SM; Montefiori, DC; Denny, TN; Moody, MA; Tomaras, GD; Gao, F; Haynes, BF
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