HIV中和抗体的多反应性/自身反应性研究进展

Neutralizing antibodies and polyreactive/autoreactive antibodies of HIV infection

广谱高效中和抗体在对抗艾滋病病毒(HIV)感染的免疫中起关键作用。HIV感染后CD4+T淋巴细胞的缺失,使依赖于T细胞的B细胞体液免疫功能受抑制,多数HIV感染者无法通过自然途径产生广谱高效中和抗体,通过设计疫苗进行人工诱导仍是主要目标。近年研究表明,部分广谱高效中和抗体具有多反应性/自身反应性,且从HIV感染者体内HIV抗原特异性B细胞克隆表达的单克隆抗体也多是多反应性/自身反应性抗体,使得多反应性抗体在对抗HIV感染领域的研究成为热点。关于这些多反应性抗体是否可提供高效的免疫保护,因此可以作为人工疫苗的诱导靶点是现阶段需要解答的重要课题。文章介绍了目前HIV高效广谱中和抗体的种类和识别位点,针对多反应性/自身反应性的HIV抗体,对其产生机制和临床意义进行全面探讨,并展望其在疫苗设计中作为诱导靶点的潜在价值。

Broad and potent neutralizing antibodies（bnAbs）are crucial elements combating HIV.After HIV infection,CD4＋T cells are gradually depleted followed by the damaged humoral response of T-dependent B cell function.It is extremely rare that the infected body can generate bnAbs naturally.Therefore,inducing bnAbs through vaccines remains the ultimate approach to protect from HIV infection.Recent studies of established anti-HIV neutralizing antibodies and a large collection of recombinant anti-gp120 antibodies derived from HIV-infected individuals show that many of these antibodies display poly-/auto-reactivity.It is key to know whether these poly-/auto-reactive antibodies can contribute to combating HIV infection and act as a new inducing target in vaccine development.This review introduces the current discovered broad and potent anti-HIV neutralizing antibodies and their possibly existing poly-/auto-reactivity.We also discuss the potential underlying mechanisms of the generation of such poly-/autoreactive anti-HIV antibodies,and their clinical significance related to AIDS.Finally,we expect that polyreactive antibody may have important roles in immune protection and polyreactive antibody can be used as the inducing target in vaccine development.