Y. R. Gaitonde Center for AIDS Research and Education (YRG CARE), Rajiv Gandhi Road, Taramani, Chennai 600113, India.
Laboratory-based department, UniKL Royal College of Medicine Perak (UniKL RCMP), Universiti Kuala Lumpur, Jalan Greentown, Ipoh 30450, Malaysia.
Pathog Dis. 2019 Jun 1;77(4). doi: 10.1093/femspd/ftz044.
HIV-1 vaccine functioning relies on successful induction of broadly neutralizing antibodies (bNAbs). CXCR3- circulatory T-follicular helper (cTfh) cells are necessary for inducing B-cells for generating bNAbs. Recent studies have suggested that CXCR3+ Tfh cells might also influence bNAb production. Plasma samples from 34 ART-Naïve HIV-1 infected individuals [long-term nonprogressors (LTNP)-19; Progressors-13] were tested against a heterologous virus panel (n = 11) from subtypes A, B, C, G, AC, BC and AE. Frequencies of CXCR3+ and CXCR3- cTfh-like cells in peripheral circulation were studied using flow cytometry. LTNP showed significantly lower CXCR3+ and higher CXCR3- cTfh-like cell frequencies, while neutralization breadth was observed to be broader in progressors. A positive correlation was observed between bNAb breadth and potency with CXCR3+PD-1+ cTfh-like cells in LTNP. Based on neutralization breadth, 9 HIV-1 infected individuals were classified as 'top neutralizers' and 23 as 'low neutralizers' and they did not show any correlations with CXCR3+ and CXCR3- cTfh-like cells. These preliminary data suggest that CXCR3+ similar to CXCR3- might possess significant functional properties for driving B-cells to produce bNAbs. Hence, an HIV vaccine which is capable of optimal induction of CXCR3+ cTfh cells at germinal centers might confer superior protection against HIV.
HIV-1 疫苗的作用依赖于成功诱导广泛中和抗体 (bNAbs)。CXCR3-循环滤泡辅助 T 细胞 (cTfh) 对于诱导 B 细胞产生 bNAbs 是必需的。最近的研究表明,CXCR3+Tfh 细胞也可能影响 bNAb 的产生。对 34 名未经抗逆转录病毒治疗 (ART) 的 HIV-1 感染个体 [长期非进展者 (LTNP)-19;进展者-13] 的血浆样本进行了检测,使用的是来自亚型 A、B、C、G、AC、BC 和 AE 的异源病毒组 (n=11)。使用流式细胞术研究外周循环中 CXCR3+和 CXCR3-cTfh 样细胞的频率。LTNP 表现出明显更低的 CXCR3+和更高的 CXCR3-cTfh 样细胞频率,而进展者的中和广度则观察到更宽。在 LTNP 中,观察到 bNAb 广度和效力与 CXCR3+PD-1+cTfh 样细胞之间存在正相关。基于中和广度,将 9 名 HIV-1 感染者归类为“顶级中和者”,23 名归类为“低中和者”,他们与 CXCR3+和 CXCR3-cTfh 样细胞没有任何相关性。这些初步数据表明,CXCR3+与 CXCR3-类似,可能具有显著的功能特性,可驱动 B 细胞产生 bNAb。因此,能够在生发中心最佳诱导 CXCR3+cTfh 细胞的 HIV 疫苗可能会提供针对 HIV 的卓越保护。
Front Immunol. 2019-7-2