美国国立卫生研究院John R. Mascola研究组取得一项新突破。他们发现具有疫苗诱导的抗原结合热区的抗体谱系，能够中和广泛的艾滋病毒。 2019年7月25日，国际知名学术期刊《细胞》发表了这一成果。

为了了解如何诱导广泛性中和抗体(bNAbs)，该课题组人员在接种疫苗的猕猴中识别、鉴定并跟踪了靶向HIV-1-融合肽(FP)的5个中和抗体谱系。遗传和结构分析显示，其中两个谱系属于一个可重现的类别，能够中和208种不同病毒株中的59%。B细胞分析表明，这5个谱系都是通过FP-载体致敏启动和扩增的，通过包膜(Env)-三聚体促进诱导交叉反应中和。这些抗体的结合能热区集中在FP，而单独的Env三聚体免疫诱导的几种FP定向抗体则较少集中在FP，且具有较弱的广谱中和性。利用FP等保守的亚区致敏，可以诱导出结合能热区与目标亚区一致的抗体，并具有广泛的中和能力。

据了解，通过疫苗介导，诱导出能够中和多种HIV-1毒株的抗体，一直是研究者长期的目标。

附：英文原文

Title: Antibody Lineages with Vaccine-Induced Antigen-Binding Hotspots Develop Broad HIV Neutralization

Author: Rui Kong, Hongying Duan, Zizhang Sheng, Lawrence Shapiro, Peter D. Kwong, John R. Mascola, et al

Issue&Volume: 25 JULY 2019

Abstract: The vaccine-mediated elicitation of antibodies (Abs) capable of neutralizing diverse HIV-1 strains has been a long-standing goal. To understand how broadly neutralizing antibodies (bNAbs) can be elicited, we identified, characterized, and tracked five neutralizing Ab lineages targeting the HIV-1-fusion peptide (FP) in vaccinated macaques over time. Genetic and structural analyses revealed two of these lineages to belong to a reproducible class capable of neutralizing up to 59% of 208 diverse viral strains. B cell analysis indicated each of the five lineages to have been initiated and expanded by FP-carrier priming, with envelope (Env)-trimer boosts inducing cross-reactive neutralization. These Abs had binding-energy hotspots focused on FP, whereas several FP-directed Abs induced by immunization with Env trimer-only were less FP-focused and less broadly neutralizing. Priming with a conserved subregion, such as FP, can thus induce Abs with binding-energy hotspots coincident with the target subregion and capable of broad neutralization.

DOI: https://doi.org/10.1016/j.cell.2019.06.030

Source: https://www.cell.com/cell/fulltext/S0092-8674(19)30733-0