Immunization and Immune Monitoring

免疫和免疫监测

• 批准号: 7896719
• 负责人: David C Montefiori
• 金额: $ 179.55万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7896719
• 关键词: Acute; Antibodies; Antibody Formation; Antibody Specificity; Autologous; Beds; Blood Banks; Data; Enzyme-Linked Immunosorbent Assay; Epitopes; Evolution; HIV vaccine; HIV-1; Immunization; Immunologic Monitoring; Immunology; Individual; Infection; Kinetics; Length; Maps; Mediating; Participant; Plasma; Sampling; Serum; Site; South Africa; Specificity; Vaccine Design; Virus; Work; glycosylation; insight; neutralizing antibody; response; vaccine development

Neutralizing antibody responses in acute HIV-1 subtype C infection The study of the evolution and specificities of neutralizing antibodies during the course of 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 response in 14 HIV-1 subtype C infected individuals using envelope clones obtained within the first 2 months post-infection. Our data shows that potent, but relatively strain-specific, neutralizing antibodies develop within 3-12 months of HIV-1 infection. The magnitude of this response was associated with shorter envelope length 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 epitopes developed to high titer in 12 participants and in most cases before autologous neutralizing antibodies. However, neither anti-MPER nor anti-CD4i antibody specificities conferred neutralization breadth, at least within the first year of infection. These data provide insights into the kinetics, potency, breadth, and epitope specificity of neutralizing antibody responses in acute HIV-1 subtype C infection. Mapping the specificity of broadly neutralizing sera HIV-1 positive plasma samples obtained from the South Africa blood bank were used to determine whether neutralization breadth was associated with anti-CD4i or anti-MPER antibodies. The BED ELISA was performed to exclude samples from donors with recent infection which may confound the analysis.

急性 HIV-1 C 亚型感染中的中和抗体反应 HIV-1感染过程中中和抗体的演变和特异性研究 对于发现疫苗设计的可能目标可能很重要。在这项研究中，我们评估了 使用 14 名 HIV-1 C 亚型感染者的自体和异体中和反应 感染后前 2 个月内获得的包膜克隆。我们的数据表明，有效但相对而言 HIV-1 感染后 3-12 个月内会产生毒株特异性中和抗体。这件事的严重程度 反应与较短的包膜长度和较少的糖基化位点相关，特别是在 V1-V2 中 地区。感染一年内，14 人中有 4 人检测到抗 MPER 抗体，而抗体 在 12 名参与者中，CD4 诱导的表位已发展到高滴度，并且大多数情况下是在自体同源之前 中和抗体。然而，抗 MPER 和抗 CD4i 抗体均未赋予特异性。 中和广度，至少在感染的第一年内。这些数据提供了对动力学的见解， 急性 HIV-1 C 亚型中和抗体反应的效力、广度和表位特异性 感染。 绘制广泛中和血清的特异性 使用从南非血库获得的 HIV-1 阳性血浆样本来确定是否 中和广度与抗 CD4i 或抗 MPER 抗体相关。 BED ELISA 是 这样做是为了排除来自近期感染的捐赠者的样本，这可能会混淆分析。