HIV-1抗体的进化

marine0425030

Maturation and Diversity of the VRC01-Antibody Lineage over 15 Years of Chronic HIV-1 Infection

Cell, Volume 161, Issue3,  p470–485, 23 April 2015

Highlights

• A diverse multi-clade antibody repertoire can develop from a single B cell
• Rate of antibody evolution in long-lived lineages is similar to that of HIV-1
• High lineage evolutionary rate over years enables extraordinary antibody diversity
• An antibody lineage can encompass divergent loop and disulfide structures
  

Summary
HIV-1-neutralizing antibodies develop in most HIV-1-infected individuals, although highly effective antibodies are generally observed only after years of chronic infection. Here, we characterize the rate of maturation and extent of diversity for the lineage that produced the broadly neutralizing antibody VRC01 through longitudinal sampling of peripheral B cell transcripts over 15 years and co-crystal structures of lineage members. Next-generation sequencing identified VRC01-lineage transcripts, which encompassed diverse antibodies organized into distinct phylogenetic clades. Prevalent clades maintained characteristic features of antigen recognition, though each evolved binding loops and disulfides that formed distinct recognition surfaces. Over the course of the study period, VRC01-lineage clades showed continuous evolution, with rates of ∼2 substitutions per 100 nucleotides per year, comparable to that of HIV-1 evolution. This high rate of antibody evolution provides a mechanism by which antibody lineages can achieve extraordinary diversity and, over years of chronic infection, develop effective HIV-1 neutralization.

marine0425030

HIV抗体研究热点：1.利用广谱抗体进行治疗，2.还有就是类似与上文的，去追溯抗体的形成，再尝试着如何利用好的抗原去诱导出广谱抗体来，进而利用与疫苗开发。