Horwitz Joshua A, Bar-On Yotam, Lu Ching-Lan, Fera Daniela, Lockhart Ainsley A K, Lorenzi Julio C C, Nogueira Lilian, Golijanin Jovana, Scheid Johannes F, Seaman Michael S, Gazumyan Anna, Zolla-Pazner Susan, Nussenzweig Michel C
Laboratory of Molecular Immunology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA; Laboratory of Structural Cell Biology, Harvard Medical School, 250 Longwood Avenue, Boston, MA 02115, USA; Whelan Laboratory, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
Laboratory of Molecular Immunology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
Cell. 2017 Aug 10;170(4):637-648.e10. doi: 10.1016/j.cell.2017.06.048. Epub 2017 Jul 27.
Non-neutralizing antibodies (nnAbs) to HIV-1 show little measurable activity in prevention or therapy in animal models yet were the only correlate of protection in the RV144 vaccine trial. To investigate the role of nnAbs on HIV-1 infection in vivo, we devised a replication-competent HIV-1 reporter virus that expresses a heterologous HA-tag on the surface of infected cells and virions. Anti-HA antibodies bind to, but do not neutralize, the reporter virus in vitro. However, anti-HA protects against infection in humanized mice and strongly selects for nnAb-resistant viruses in an entirely Fc-dependent manner. Similar results were also obtained with tier 2 HIV-1 viruses using a human anti-gp41 nnAb, 246D. While nnAbs are demonstrably less effective than broadly neutralizing antibodies (bNAbs) against HIV-1 in vitro and in vivo, the data show that nnAbs can protect against and alter the course of HIV-1 infection in vivo. PAPERCLIP.
针对HIV-1的非中和抗体（nnAbs）在动物模型的预防或治疗中几乎没有可测量的活性，但却是RV144疫苗试验中唯一的保护相关因素。为了研究nnAbs在体内对HIV-1感染的作用，我们设计了一种具有复制能力的HIV-1报告病毒，该病毒在受感染细胞和病毒粒子的表面表达一种异源HA标签。抗HA抗体在体外可与报告病毒结合，但不能中和该病毒。然而，抗HA可保护人源化小鼠免受感染，并以完全依赖Fc的方式强烈选择对nnAb耐药的病毒。使用人抗gp41 nnAb 246D对2型HIV-1病毒进行实验也获得了类似结果。虽然在体外和体内，nnAbs对HIV-1的有效性明显低于广泛中和抗体（bNAbs），但数据表明nnAbs在体内可预防并改变HIV-1感染的进程。回形针。
