Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98195, USA.
Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98195, USA; Medical Scientist Training Program, University of Washington School of Medicine, Seattle, WA 98195, USA.
Cell Rep. 2018 Apr 17;23(3):682-691. doi: 10.1016/j.celrep.2018.03.082.
Eliciting broad and potent HIV-specific neutralizing antibody responses represents the holy grail of HIV vaccine efforts. Data from singly infected individuals with broad and potent plasma neutralizing activity targeting one epitope have guided our understanding of how these responses develop. However, far less is known about responses developed by superinfected individuals who acquire two distinct HIV strains. Here, we isolated HIV-specific mAbs from a superinfected individual with a broad plasma response. In this superinfection case, neutralizing activity resulted from multiple distinct B cell lineages that arose in response to either the initial or the superinfecting virus, including an antibody that targets the N332 supersite. This nAb, QA013.2, was specific to the superinfecting virus and was associated with eventual reemergence of the initial infecting virus. The complex dynamic between viruses in superinfection may drive development of a unique collection of polyclonal nAbs that present a higher barrier to escape than monoclonal responses.
诱导广泛而有效的 HIV 特异性中和抗体反应是 HIV 疫苗研究的圣杯。具有针对单一表位的广泛而有效的血浆中和活性的单一感染个体的数据指导了我们对这些反应如何发展的理解。然而，对于通过再次感染获得两种不同 HIV 毒株的个体所产生的反应，我们了解得要少得多。在这里，我们从一名具有广泛血浆反应的再次感染个体中分离出 HIV 特异性单克隆抗体。在这种再次感染的情况下，中和活性来自于多个不同的 B 细胞谱系，这些谱系是针对初始病毒或再次感染病毒而产生的，包括一种针对 N332 超位点的抗体。这种 nAb，QA013.2，是针对再次感染病毒的，并且与初始感染病毒的最终再次出现有关。再次感染中病毒之间的复杂动态可能会促使产生独特的多克隆 nAb 集合，这些 nAb 比单克隆反应具有更高的逃逸障碍。
