PDF(Pubmed)
Abstract：
Viral infection generally induces polyclonal neutralizing antibody responses. However, how many lineages of antibody responses can fully represent the neutralization activities in sera has not been well studied. Using the newly designed stable HIV-1 Env trimer as hook, we isolated two distinct broadly neutralizing antibodies (bnAbs) from Chinese rhesus macaques infected with SHIV1157ipd3N4 for 5 years. One lineage of neutralizing antibodies (JT15 and JT16) targeted the V2-apex in the Env trimers, similar to the J038 lineage bnAbs identified in our previous study. The other lineage neutralizing antibody (JT18) targeted the V3 crown region in the Env, which strongly competed with human 447-52D. Each lineage antibody neutralized a different set of viruses. Interestingly, when the two neutralizing antibodies from different lineages isolated from the same macaque were combined, the mixture had a neutralization breath very similar to that from the cognate sera. Our study demonstrated that a minimum of two different neutralizing antibodies can fully recapitulate the serum neutralization breadth. This observation can have important implications in AIDS vaccine design.
摘要：
病毒感染通常诱导多克隆中和抗体应答。然而,有多少谱系的抗体反应可以完全代表血清中的中和活性还没有得到很好的研究。使用新设计的稳定的HIV-1Env三聚体作为钩子，我们从感染SHIV1157ipd3N4的中国恒河猴中分离出两种不同的广泛中和抗体（bnAb），为期5年。一种中和抗体（JT15和JT16）靶向Env三聚体中的V2顶点，与我们先前研究中鉴定的J038谱系bnAb相似。另一种谱系中和抗体（JT18）靶向Env中的V3冠区，与人类447-52D竞争激烈。每种谱系抗体中和一组不同的病毒。有趣的是,当从同一只猕猴中分离的来自不同谱系的两种中和抗体组合时，该混合物具有与同源血清非常相似的中和呼吸。我们的研究表明，至少两种不同的中和抗体可以完全概括血清中和宽度。这一观察结果对AIDS疫苗设计具有重要意义。
