Development of glycan-binding broadly neutralizing antibody responses in HIV-1 infection

HIV-1包膜（Env）是中和抗体的唯一靶标，因此是疫苗开发的主要候选物。HIV-1响应于宿主免疫系统而快速突变，导致Env序列的高度多样性，这代表了疫苗开发的主要挑战。然而，10-30%的HIV-1感染患者在感染2-3年后将产生能够中和多种HIV-1毒株的广泛中和抗体（bnAb），这为可能实现具有广泛保护的HIV-1疫苗提供了一些希望。从慢性感染患者中分离bnAb，可以鉴定和表征HIV-1 Env上的中和表位。然而，开发能够引发bnAb的HIV-1疫苗的尝试迄今为止尚未成功。因此，更详细地了解HIV-1 bnAbs在感染期间如何在体内进化可能为下一代HIV-1疫苗的开发提供见解。通过研究HIV-1感染个体的队列（SPARTAC）中的纵向血清应答，我们鉴定了开发靶向N332/V3表位Env的bNAb的供体（SJU供体）。该供体感染了分化体C病毒，并在感染后1-2年后产生了bNAb。尽管产生了bnAb应答，但SJU供体被第二种HIV-1病毒双重感染。该供体提供了研究bnAb发育和研究bnAb逃逸的重要机会。对这些领域的进一步了解将有助于HIV-1免疫原的合理设计。

HIV-1 Envelope (Env) is the sole target for neutralizing antibodies and therefore the primary candidate for vaccine development. HIV-1 rapidly mutates in response to the host immune system leading to a high-diversity in Env sequence which represents a major challenge for vaccine development. However, 10-30% of HIV-1 infected patients after 2-3 years of infection will develop broadly neutralizing antibodies (bnAbs) that are capable of neutralizing a wide number of HIV-1 strains offering some promise that an HIV-1 vaccine with broad protection might be achieved. Isolation of bnAbs from chronically infected patients has allowed identification and characterisation of the neutralization epitopes on HIV-1 Env. However, attempts to develop an HIV-1 vaccine that is able to elicit bnAbs have thus far been unsuccessful. Therefore, a more detailed knowledge on how HIV-1 bnAbs evolve in vivo during infection may provide insights into development of next generation HIV-1 vaccines. Through studying longitudinal serum responses in a cohort (SPARTAC) of HIV-1 infected individuals, we have identified a donor (SJU donor) who developed bNAbs targeting the N332/V3 epitope Env. This donor was infected with a Clade C virus and developed bNAbs after 1-2 years after infection. Despite generation of a bnAb response, SJU donor became superinfected with a second HIV-1 virus. This donor presents an important opportunity to study bnAb development and study bnAb escape. Further understanding in these areas will aid in the rational design of HIV-1 immunogens.