PDF(Pubmed)
Abstract：
A limited subset of HIV-1 infected adult individuals typically after at least 2-3 years of chronic infection, develop broadly neutralizing antibodies (bnAbs), suggesting that highly conserved neutralizing epitopes on the HIV-1 envelope glycoprotein are difficult for B cell receptors to effectively target, during natural infection. Recent studies have shown the evolution of bnAbs in HIV-1 infected infants.
We used bulk BCR sequencing (BCR-seq) to profile the B cell receptors from longitudinal samples (3 time points) collected from a rare pair of antiretroviralnaïve, HIV-1 infected pediatric monozygotic twins (AIIMS_329 and AIIMS_330) who displayed elite plasma neutralizing activity against HIV-1.
BCR-seq of both twins revealed convergent antibody characteristics including V-gene use, CDRH3 lengths and somatic hypermutation (SHM). Further, antibody clonotypes with genetic features similar to highly potent bnAbs isolated from adults showed ongoing development in donor AIIMS_330 but not in AIIMS_329, corroborating our earlier findings based on plasma bnAbs responses. An increase in SHM was observed in sequences of the IgA isotype from AIIMS_330.
This study suggests that children living with chronic HIV-1 can develop clonotypes of HIV-1 bnAbs against multiple envelope epitopes similar to those isolated from adults, highlighting that such B cells could be steered to elicit bnAbs responses through vaccines aimed to induce bnAbs against HIV-1 in a broad range of people including children.
We used bulk BCR sequencing (BCR-seq) to profile the B cell receptors from longitudinal samples (3 time points) collected from a rare pair of antiretroviralnaïve, HIV-1 infected pediatric monozygotic twins (AIIMS_329 and AIIMS_330) who displayed elite plasma neutralizing activity against HIV-1.
BCR-seq of both twins revealed convergent antibody characteristics including V-gene use, CDRH3 lengths and somatic hypermutation (SHM). Further, antibody clonotypes with genetic features similar to highly potent bnAbs isolated from adults showed ongoing development in donor AIIMS_330 but not in AIIMS_329, corroborating our earlier findings based on plasma bnAbs responses. An increase in SHM was observed in sequences of the IgA isotype from AIIMS_330.
This study suggests that children living with chronic HIV-1 can develop clonotypes of HIV-1 bnAbs against multiple envelope epitopes similar to those isolated from adults, highlighting that such B cells could be steered to elicit bnAbs responses through vaccines aimed to induce bnAbs against HIV-1 in a broad range of people including children.
摘要：
■通常在慢性感染至少2-3年后，开发广泛中和抗体（bnAbs），提示HIV-1包膜糖蛋白上高度保守的中和表位难以有效靶向B细胞受体,在自然感染期间。最近的研究表明bnAb在HIV-1感染的婴儿中的进化。
■我们使用批量BCR测序（BCR-seq）从一对罕见的抗逆转录病毒原初收集的纵向样品（3个时间点）中描绘B细胞受体，HIV-1感染的小儿单卵双胞胎（AIIMS_329和AIIMS_330）显示出针对HIV-1的血浆中和活性。
■两个双胞胎的BCR-seq显示了会聚的抗体特征，包括V基因的使用，CDRH3长度和体细胞超突变(SHM)。Further,具有与从成人分离的高效bnAb相似的遗传特征的抗体克隆型在供体AIIMS_330中显示出持续发展,但在AIIMS_329中没有,这证实了我们基于血浆bnAb反应的早期发现.在来自AIIMS_330的IgA同种型的序列中观察到SHM的增加。
这项研究表明，患有慢性HIV-1的儿童可以针对多种包膜表位发展出HIV-1bnAb的克隆型，类似于从成人中分离出的抗原表位，强调这种B细胞可以通过旨在在包括儿童在内的广泛人群中诱导针对HIV-1的bnAbs的疫苗来引发bnAbs反应。
■我们使用批量BCR测序（BCR-seq）从一对罕见的抗逆转录病毒原初收集的纵向样品（3个时间点）中描绘B细胞受体，HIV-1感染的小儿单卵双胞胎（AIIMS_329和AIIMS_330）显示出针对HIV-1的血浆中和活性。
■两个双胞胎的BCR-seq显示了会聚的抗体特征，包括V基因的使用，CDRH3长度和体细胞超突变(SHM)。Further,具有与从成人分离的高效bnAb相似的遗传特征的抗体克隆型在供体AIIMS_330中显示出持续发展,但在AIIMS_329中没有,这证实了我们基于血浆bnAb反应的早期发现.在来自AIIMS_330的IgA同种型的序列中观察到SHM的增加。
这项研究表明，患有慢性HIV-1的儿童可以针对多种包膜表位发展出HIV-1bnAb的克隆型，类似于从成人中分离出的抗原表位，强调这种B细胞可以通过旨在在包括儿童在内的广泛人群中诱导针对HIV-1的bnAbs的疫苗来引发bnAbs反应。
