Infants of HIV-positive mothers can acquire HIV infection by various routes, but even in the absence of antiviral treatment, the majority of these infants do not become infected. There is evidence that maternal antibodies provide some protection from infection, but gestational maternal antibodies have not yet been characterized in detail. One of the most studied vertically infected infants is BG505, as the virus from this infant yielded an Envelope protein that was successfully developed as a stable trimer. Here, we isolated and characterized 39 HIV-specific neutralizing monoclonal antibodies (nAbs) from MG505, the mother of BG505, at a time point just prior to vertical transmission. These nAbs belonged to 21 clonal families and employed a variety of VH genes. Many were specific for the HIV-1 Env V3 loop, and this V3 specificity correlated with measurable antibody-dependent cellular cytotoxicity (ADCC) activity. The isolated nAbs did not recapitulate the full breadth of heterologous or autologous virus neutralization by contemporaneous plasma. Notably, we found that the V3-targeting nAb families neutralized one particular maternal Env variant, even though all tested variants had low V3 sequence diversity and were measurably bound by these nAbs. None of the nAbs neutralized BG505 transmitted virus. Furthermore, the MG505 nAb families were found at relatively low frequencies within the maternal B cell repertoire; all were less than 0.25% of total IgG sequences. Our findings illustrate an example of the diversity of HIV-1 nAbs within one mother, cumulatively resulting in a collection of antibody specificities that can contribute to the transmission bottleneck.IMPORTANCE Mother-to-child-transmission of HIV-1 offers a unique setting in which maternal antibodies both within the mother and passively transferred to the infant are present at the time of viral exposure. Untreated HIV-exposed human infants are infected at a rate of 30 to 40%, meaning that some infants do not get infected despite continued exposure to virus. Since the potential of HIV-specific immune responses to provide protection against HIV is a central goal of HIV vaccine design, understanding the nature of maternal antibodies may provide insights into immune mechanisms of protection. In this study, we isolated and characterized HIV-specific antibodies from the mother of an infant whose transmitted virus has been well studied.

中文翻译：

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垂直传播时母体 HIV-1 特异性抗体的多样性和功能。


艾滋病毒呈阳性的母亲的婴儿可以通过多种途径感染艾滋病毒，但即使在没有抗病毒治疗的情况下，这些婴儿中的大多数也不会被感染。有证据表明母体抗体可提供一定程度的感染保护，但妊娠期母体抗体尚未得到详细表征。研究最多的垂直感染婴儿之一是 BG505，因为该婴儿的病毒产生了一种包膜蛋白，该蛋白已成功开发为稳定的三聚体。在这里，我们在垂直传播之前的时间点从 BG505 的母亲 MG505 中分离并鉴定了 39 种 HIV 特异性中和单克隆抗体 (nAb)。这些 nAb 属于 21 个克隆家族，并采用多种 VH 基因。许多对 HIV-1 Env V3 环具有特异性，并且这种 V3 特异性与可测量的抗体依赖性细胞毒性 (ADCC) 活性相关。分离的 nAb 并不能概括同期血浆中和异源或自体病毒的全部范围。值得注意的是，我们发现 V3 靶向 nAb 家族中和了一种特定的母体 Env 变体，尽管所有测试的变体都具有较低的 V3 序列多样性并且可测量地与这些 nAb 结合。没有一种 nAb 能中和 BG505 传播的病毒。此外，在母体 B 细胞库中发现 MG505 nAb 家族的频率相对较低；全部都小于总 IgG 序列的 0.25%。我们的研究结果说明了一位母亲体内 HIV-1 nAb 的多样性，累积导致了一系列可能导致传播瓶颈的抗体特异性。重要性 HIV-1 的母婴传播提供了一种独特的环境，在病毒暴露时，母体抗体既存在于母亲体内，又被动转移给婴儿。未经治疗的暴露于艾滋病毒的人类婴儿的感染率为 30% 至 40%，这意味着有些婴儿尽管持续接触病毒却不会被感染。由于艾滋病毒特异性免疫反应提供针对艾滋病毒的保护的潜力是艾滋病毒疫苗设计的核心目标，因此了解母体抗体的性质可能有助于深入了解免疫保护机制。在这项研究中，我们从一名婴儿的母亲中分离和鉴定了艾滋病毒特异性抗体，该婴儿的传播病毒已得到充分研究。