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Antibody-dependent cellular cytotoxicity responses and susceptibility influence HIV-1 mother-to-child transmission
Allison S. Thomas, … , Athena P. Kourtis, Manish Sagar
Allison S. Thomas, … , Athena P. Kourtis, Manish Sagar
Published March 24, 2022
Citation Information: JCI Insight. 2022;7(9):e159435. https://doi.org/10.1172/jci.insight.159435.
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Research Article AIDS/HIV Infectious disease

Antibody-dependent cellular cytotoxicity responses and susceptibility influence HIV-1 mother-to-child transmission

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Abstract

HIV-1 vaccine efforts are primarily directed toward eliciting neutralizing antibodies (nAbs). However, vaccine trials and mother-to-child natural history cohort investigations indicate that antibody-dependent cellular cytotoxicity (ADCC), not nAbs, correlate with prevention. The ADCC characteristics associated with lack of HIV-1 acquisition remain unclear. Here, we examine ADCC and nAb properties in pretransmission plasma from HIV-1–exposed infants and from the corresponding transmitting and nontransmitting mothers’ breast milk and plasma. Breadth and potency (BP) were assessed against a panel of heterologous, nonmaternal variants. ADCC and neutralization sensitivity were estimated for the strains in the infected mothers. Infants who eventually acquired HIV-1 and those who remained uninfected had similar pretransmission ADCCBP. Viruses circulating in the transmitting and nontransmitting mothers had similar ADCC susceptibility. Infants with higher pretransmission ADCCBP and exposure to more ADCC-susceptible strains were less likely to acquire HIV-1. In contrast, higher preexisting infant neutralization BP and greater maternal virus neutralization sensitivity did not associate with transmission. Infants had higher ADCCBP closer to birth and in the presence of high plasma IgG relative to IgA levels. Mothers with potent humoral responses against their autologous viruses harbored more ADCC-sensitive strains. ADCC sensitivity of the exposure variants and preexisting ADCCBP influenced mother-to-child HIV-1 transmission during breastfeeding. Vaccination strategies that enhance ADCC are likely insufficient to prevent HIV-1 transmission because some strains may have low ADCC susceptibility.

Authors

Allison S. Thomas, Carolyn Coote, Yvetane Moreau, John E. Isaac, Alexander C. Ewing, Athena P. Kourtis, Manish Sagar

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Figure 3

Infant ADCC responses and ADCC sensitivity of the exposure strains associate with transmission.

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Infant ADCC responses and ADCC sensitivity of the exposure strains assoc...
ADCC sensitivity of TM and NTM viruses to (A) pool of maternal plasma and (B) bnAbs. (C) ADCC susceptibility correlation to maternal pool and bnAbs. Combined statistic of infant ADCCBP and sensitivity of TM and NTM strains to (D) maternal pool — ADCCAUC (maternal pool) — or (E) bnAbs — ADCCAUC (bnAb pool) — among HEI and HEU infants. (F) Neutralization susceptibility of TM and NTM Envs to maternal plasma pool and (G) combined statistic of infant NeutBP and neutralization susceptibility of the exposure strains. Colors signify matched pairs. Bars show mean and standard error. Group comparisons were done using Wilcoxon’s rank-sum test for A and B, Welch’s t test for D–G, and/or multivariable logistic regression for D, E, and G. Correlations were assessed using Spearman’s statistic. *P ≤ 0.05 with 1 of these statistical tests. All values are means from a minimum of 2 replicates.

Copyright © 2023 American Society for Clinical Investigation
ISSN 2379-3708

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