HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.
Virology. 2012 Nov 25;433(2):410-20. doi: 10.1016/j.virol.2012.08.033. Epub 2012 Sep 18.
Neutralizing (nAbs) and high affinity binding antibodies may be critical for an efficacious HIV-1 vaccine. We characterized virus-specific nAbs and binding antibody responses over 21 months in eight HIV-1 subtype C chronically infected individuals with heterogeneous rates of disease progression. Autologous nAb titers of study exit plasma against study entry viruses were significantly higher than contemporaneous responses at study entry (p=0.002) and exit (p=0.01). NAb breadth and potencies against subtype C viruses were significantly higher than for subtype A (p=0.03 and p=0.01) or B viruses (p=0.03; p=0.05) respectively. Gp41-IgG binding affinity was higher than gp120-IgG (p=0.0002). IgG-FcγR1 affinity was significantly higher than FcγRIIIa (p<0.005) at study entry and FcγRIIb (p<0.05) or FcγRIIIa (p<0.005) at study exit. Evolving IgG binding suggests alteration of immune function mediated by binding antibodies. Evolution of nAbs was a potential marker of HIV-1 disease progression.
中和 (nAbs) 和高亲和力结合抗体可能对有效的 HIV-1 疫苗至关重要。我们在 8 名 HIV-1 亚型 C 慢性感染者中，在 21 个月的时间内对病毒特异性 nAbs 和结合抗体反应进行了特征描述，这些感染者的疾病进展速度存在差异。与研究开始时的病毒相比，研究结束时的个体自身 nAb 滴度对研究进入病毒的反应明显更高（p=0.002）和退出（p=0.01）。与亚型 A（p=0.03 和 p=0.01）或 B（p=0.03；p=0.05）病毒相比，nAb 的广度和对亚型 C 病毒的效力明显更高。gp41-IgG 结合亲和力高于 gp120-IgG（p=0.0002）。在研究开始时，IgG-FcγR1 亲和力明显高于 FcγRIIIa（p<0.005），在研究结束时，FcγRIIb（p<0.05）或 FcγRIIIa（p<0.005）。不断演变的 IgG 结合表明结合抗体介导的免疫功能发生改变。nAbs 的进化可能是 HIV-1 疾病进展的潜在标志物。
