Kelsoe Garnett, Haynes Barton F
Departments of Immunology and Medicine, Duke University School of Medicine, Duke Human Vaccine Institute, Durham, NC, 27710, USA.
Immunol Rev. 2017 Jan;275(1):79-88. doi: 10.1111/imr.12508.
Induction of broadly neutralizing antibodies (bNAbs) is a major goal of HIV vaccine development. BNAbs are made during HIV infection by a subset of individuals but currently cannot be induced in the setting of vaccination. Considerable progress has been made recently in understanding host immunologic controls of bNAb induction and maturation in the setting of HIV infection, and point to key roles for both central and peripheral immunologic tolerance mechanisms in limiting bnAb development. Immune tolerance checkpoint inhibition has been transformative in promotion of anti-tumor CD8 T-cell responses in the treatment of certain malignancies. Here, we review the evidence for host controls of bNAb responses, and discuss strategies for the transient modulation of immune responses with vaccines toward the goal of enhancing germinal center B-cell responses to favor bNAb B-cell lineages and to foster their maturation to full neutralization potency.
诱导广泛中和抗体（bNAb）是HIV疫苗研发的主要目标。bNAb由一部分个体在HIV感染期间产生，但目前在疫苗接种情况下无法诱导产生。最近在理解HIV感染背景下宿主对bNAb诱导和成熟的免疫控制方面取得了相当大的进展，这表明中枢和外周免疫耐受机制在限制bnAb产生中起关键作用。免疫耐受检查点抑制在某些恶性肿瘤治疗中促进抗肿瘤CD8 T细胞反应方面具有变革性。在此，我们综述宿主对bNAb反应控制的证据，并讨论通过疫苗对免疫反应进行短暂调节的策略，以增强生发中心B细胞反应，有利于bNAb B细胞谱系，并促进其成熟至完全中和效力。
