State Key Laboratory of Infectious Disease Prevention and Control, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Beijing 102206, PR China.
Departments of Experimental Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
Sci Rep. 2017 Apr 7;7:46308. doi: 10.1038/srep46308.
Characterizing neutralizing antibody (NAb) responses in individuals infected with diverse HIV-1 strains is necessary to reveal the novel targets for regional preventive and therapeutic strategies development. We evaluated the prevalence, breadth, and potency of NAb responses in 98 CRF07_BC-infected individuals using a large, multi-subtype panel of 30 tier 2-3 Env-pseudotyped viruses. Furthermore, we compared the neutralization pattern of CRF07_BC-infected people with that of subtype B'-infected individuals in China. Of the 98 plasma samples tested, 18% neutralized more than 80% of viruses in the panel, and 53% neutralized more than 50%, suggesting the presence of broadly NAbs in these individuals. A preferential intra-subtype neutralization of CRF07_BC was found. Notably, CRF07_BC-infected individuals generated higher neutralization titers against intra-subtype viruses than subtype B'-infected individuals with longer infection length. However, subtype B'-infected individuals mounted broader neutralization responses against inter-subtype viruses than CRF07_BC infection with shorter infection time, indicating the transition from narrow autologous to broad heterologous neutralization over time. Neutralization activity of the top six plasmas from each cohort was attributable to IgG fraction, and half of them developed CD4 binding site antibody reactivity. Heatmap analysis identified three statistically robust clusters of plasmas that offer valuable resources for further in-depth virological and immunological study.
对感染不同 HIV-1 毒株的个体中的中和抗体 (NAb) 反应进行特征分析，对于揭示新的区域性预防和治疗策略开发目标非常必要。我们使用一个包含 30 种 2-3 级包膜假型病毒的大型多亚型面板，评估了 98 名 CRF07_BC 感染者中 NAb 反应的流行率、广度和效力。此外，我们比较了中国 CRF07_BC 感染者与 B'亚型感染者的中和模式。在 98 个测试的血浆样本中，有 18%的样本能中和该面板中超过 80%的病毒，53%的样本能中和超过 50%的病毒，这表明这些个体中存在广泛的 NAb。发现 CRF07_BC 存在偏向于同亚型的中和。值得注意的是，与感染时间较长的 B'亚型感染者相比，CRF07_BC 感染者针对同亚型病毒产生了更高的中和滴度。然而，与 CRF07_BC 感染相比，感染时间较短的 B'亚型感染者对跨亚型病毒产生了更广泛的中和反应，表明随着时间的推移，从狭窄的自体中和向广泛的异体中和转变。来自每个队列的前六份血浆的中和活性归因于 IgG 部分，其中一半产生了 CD4 结合位点抗体反应性。热图分析确定了三个具有统计学意义的稳定血浆簇，为进一步深入的病毒学和免疫学研究提供了有价值的资源。
