Diversity and Function of Maternal HIV-1-Specific Antibodies at the Time of Vertical Transmission
Diversity and Function of Maternal HIV-1-Specific Antibodies at the Time of Vertical Transmission
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DOI：
10.1128/jvi.01594-19
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发表时间：
2020-05-01
影响因子：
5.4
通讯作者：
Overbaugh, Julie M.
中科院分区：
文献类型：
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作者：
Doepker, Laura E.;Simonich, Cassandra A.;Overbaugh, Julie M.
艾滋病毒阳性母亲的婴儿可通过各种途径感染艾滋病毒，但即使没有抗病毒治疗，这些婴儿中的大多数也不会受到感染。有证据表明，母体抗体提供了一些保护感染，但妊娠母体抗体尚未详细描述。研究最多的垂直感染婴儿之一是BG 505，因为来自该婴儿的病毒产生了一种包膜蛋白，该蛋白被成功开发为稳定的三聚体。在这里，我们从MG 505（BG 505的母亲）中分离并鉴定了39种HIV特异性中和单克隆抗体（nAb），这些抗体在垂直传播之前的时间点。这些nAb属于21个克隆家族，并采用了各种VH基因。许多对HIV-1 Env V3环具有特异性，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没有概括异源或自体病毒被同期血浆中和的全部广度。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，即使所有测试的变体具有低V3序列多样性并且可测量地被这些nAb结合。无nAb中和BG 505传播的病毒。此外，在母体B细胞库中发现MG 505 nAb家族的频率相对较低;全部低于总IgG序列的0.25%。我们的研究结果说明了一个母亲体内HIV-1 nAb多样性的一个例子，累积导致抗体特异性的集合，可以有助于传播bottlenective.IMPORTANCE母婴传播的HIV-1提供了一个独特的环境，其中母亲体内的母体抗体和被动转移到婴儿是目前在病毒暴露的时间。未经治疗的艾滋病毒暴露的人类婴儿感染率为30%至40%，这意味着一些婴儿即使继续暴露于病毒也不会感染。由于HIV特异性免疫应答提供针对HIV的保护的潜力是HIV疫苗设计的中心目标，因此了解母体抗体的性质可以提供对免疫保护机制的见解。在这项研究中，我们从一个婴儿的母亲，其传播的病毒已被很好地研究了艾滋病毒特异性抗体的分离和特点。
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.