Gray E S, Moore P L, Choge I A, Decker J M, Bibollet-Ruche F, Li H, Leseka N, Treurnicht F, Mlisana K, Shaw G M, Karim S S Abdool, Williamson C, Morris L
AIDS Virus Research Unit, National Institute for Communicable Diseases, Private Bag X4, Sandringham 2131, Johannesburg, South Africa.
J Virol. 2007 Jun;81(12):6187-96. doi: 10.1128/JVI.00239-07. Epub 2007 Apr 4.
The study of the evolution and specificities of neutralizing antibodies during the course of human immunodeficiency virus type 1 (HIV-1) infection may be important in the discovery of possible targets for vaccine design. In this study, we assessed the autologous and heterologous neutralization responses of 14 HIV-1 subtype C-infected individuals, using envelope clones obtained within the first 2 months postinfection. Our data show that potent but relatively strain-specific neutralizing antibodies develop within 3 to 12 months of HIV-1 infection. The magnitude of this response was associated with shorter V1-to-V5 envelope lengths and fewer glycosylation sites, particularly in the V1-V2 region. Anti-MPER antibodies were detected in 4 of 14 individuals within a year of infection, while antibodies to CD4-induced (CD4i) epitopes developed to high titers in 12 participants, in most cases before the development of autologous neutralizing antibodies. However, neither anti-MPER nor anti-CD4i antibody specificity conferred neutralization breadth. These data provide insights into the kinetics, potency, breadth, and epitope specificity of neutralizing antibody responses in acute HIV-1 subtype C infection.
研究人类免疫缺陷病毒1型(HIV-1)感染过程中中和抗体的演变和特异性,对于发现疫苗设计的潜在靶点可能具有重要意义。在本研究中,我们使用感染后前2个月内获得的包膜克隆,评估了14例HIV-1 C亚型感染者的自身中和反应和异源中和反应。我们的数据表明,在HIV-1感染后的3至12个月内会产生强效但相对具有毒株特异性的中和抗体。这种反应的强度与V1至V5包膜长度较短和糖基化位点较少有关,特别是在V1-V2区域。在感染后一年内,14例个体中有4例检测到抗膜近端外部区域(MPER)抗体,而12名参与者体内针对CD4诱导(CD4i)表位的抗体产生了高滴度,大多数情况下是在自身中和抗体产生之前。然而,抗MPER和抗CD4i抗体特异性均未赋予中和广度。这些数据为急性HIV-1 C亚型感染中中和抗体反应的动力学、效力、广度和表位特异性提供了见解。