Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.
Sanofi, 640 Memorial Drive, Cambridge, MA, USA.
Cell Rep. 2022 Jan 4;38(1):110199. doi: 10.1016/j.celrep.2021.110199.
Broadly neutralizing antibodies (bNAbs) represent an alternative to drug therapy for the treatment of HIV-1 infection. Immunotherapy with single bNAbs often leads to emergence of escape variants, suggesting a potential benefit of combination bNAb therapy. Here, a trispecific bNAb reduces viremia 100- to 1000-fold in viremic SHIV-infected macaques. After treatment discontinuation, viremia rebounds transiently and returns to low levels, through CD8-mediated immune control. These viruses remain sensitive to the trispecific antibody, despite loss of sensitivity to one of the parental bNAbs. Similarly, the trispecific bNAb suppresses the emergence of resistance in viruses derived from HIV-1-infected subjects, in contrast to parental bNAbs. Trispecific HIV-1 neutralizing antibodies, therefore, mediate potent antiviral activity in vivo and may minimize the potential for immune escape.
广谱中和抗体（bnAbs）为治疗 HIV-1 感染提供了一种替代药物治疗的方法。使用单一 bnAb 进行免疫治疗通常会导致逃逸变异体的出现，这表明联合使用 bnAb 治疗可能具有潜在益处。在这里，一种三特异性 bnAb 可使感染 SHIV 的猕猴的病毒血症减少 100 至 1000 倍。治疗停止后，病毒血症会短暂反弹，并通过 CD8 介导的免疫控制恢复到低水平。尽管这些病毒对其中一种亲本 bnAb 的敏感性丧失，但它们仍然对三特异性抗体敏感。同样，与亲本 bnAbs 相比，三特异性 bnAb 抑制了源自 HIV-1 感染受试者的病毒产生耐药性。因此，三特异性 HIV-1 中和抗体在体内具有强大的抗病毒活性，并且可能最大限度地减少免疫逃逸的可能性。
