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研讨展现广泛的HIV中和作用

11-0810

  疫苗诱导抗原结合热区抗体谱系展现广泛的HIV中和作用

  美国国立卫生研讨院John R. Mascola研讨组获得一项新打破。他们发现具有疫苗诱导的抗原结合热区的抗体谱系,可以中和广泛的hiv病毒。 2019年7月25日,世界闻名学术期刊《细胞》宣布了这一效果。

  为了了解怎么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辨认、判定并盯梢了靶向HIV-1-交融肽(FP)的5个中和抗体谱系。遗传和结构剖析显现,其间两个谱系归于一个可重现的类别,可以中和208种不同病毒株中的59%。B细胞剖析标明,这5个谱系都是经过FP-载体致敏发动和扩增的,经过包膜(Env)-三聚体促进诱导穿插反响中和。这些抗体的结合能热区会集在FP,而独自的Env三聚体免疫诱导的几种FP定向抗体则较少会集在FP,且具有较弱的广谱中和性。使用FP等保存的亚区致敏,可以诱导出结合能热区与方针亚区共同的抗体,并具有广泛的中和才能。

  据了解,经过疫苗介导,诱导出可以中和多种HIV-1毒株的抗体,一直是研讨者长时间的方针。

  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