Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts, USA.
Department of Medicine, Boston Medical Center, Boston, Massachusetts, USA.
JCI Insight. 2022 May 9;7(9):e159435. doi: 10.1172/jci.insight.159435.
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.
HIV-1 疫苗的研发主要集中在诱导中和抗体（nAbs）上。然而，疫苗试验和母婴自然史队列研究表明，抗体依赖的细胞毒性（ADCC）而非 nAbs 与预防相关。与缺乏 HIV-1 获得相关的 ADCC 特征尚不清楚。在这里，我们研究了 HIV-1 暴露婴儿的转导前血浆以及相应的转导和非转导母亲的母乳和血浆中的 ADCC 和 nAb 特性。针对一组异源、非母体变体评估了广度和效力（BP）。对感染母亲中的菌株估计了 ADCC 和中和敏感性。最终感染 HIV-1 的婴儿和未感染的婴儿在转导前具有相似的 ADCCBP。在转导和非转导母亲中循环的病毒具有相似的 ADCC 易感性。具有较高转导前 ADCCBP 和接触更多 ADCC 敏感菌株的婴儿不太可能感染 HIV-1。相比之下，较高的婴儿预先存在的中和 BP 和更大的母体病毒中和敏感性与传播无关。与 IgA 相比，婴儿在出生时和血浆 IgG 水平较高时具有更高的 ADCCBP。针对自身病毒产生有效体液反应的母亲携带更多 ADCC 敏感的菌株。暴露变体的 ADCC 敏感性和预先存在的 ADCCBP 影响了母乳喂养期间母婴 HIV-1 的传播。增强 ADCC 的疫苗接种策略可能不足以预防 HIV-1 传播，因为某些菌株可能具有低 ADCC 易感性。
