Sorbonne Universités, UPMC Univ Paris 06, INSERM U1135, CNRS ERL 8255, Center for Immunology and Microbial Infections - CIMI-Paris, Paris, France.
INSERM UMR_S 1109, Centre de Recherche en Immunologie et Hématologie, Faculté de Médecine, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France.
EBioMedicine. 2017 Jul;21:158-169. doi: 10.1016/j.ebiom.2017.05.029. Epub 2017 May 31.
HIV-specific broadly neutralizing antibodies (bnAbs) have been isolated from patients with high viremia but also from HIV controllers that repress HIV-1 replication. In these elite controllers (ECs), multiple parameters contribute to viral suppression, including genetic factors and immune responses. Defining the immune correlates associated with the generation of bnAbs may help in designing efficient immunotherapies. In this study, in ECs either positive or negative for the HLA-B57 protective allele, in treated HIV-infected and HIV-negative individuals, we characterized memory B cell compartments and HIV-specific memory B cells responses using flow cytometry and ELISPOT. ECs preserved their memory B cell compartments and in contrast to treated patients, maintained detectable HIV-specific memory B cell responses. All ECs presented IgG1+ HIV-specific memory B cells but some individuals also preserved IgG2+ or IgG3+ responses. Importantly, we also analyzed the capacity of sera from ECs to neutralize a panel of HIV strains including transmitted/founder virus. 29% and 21% of HLA-B57+ and HLA-B57- ECs, respectively, neutralized at least 40% of the viral strains tested. Remarkably, in HLA-B57+ ECs the frequency of HIV-Env-specific memory B cells correlated positively with the neutralization breadth suggesting that preservation of HIV-specific memory B cells might contribute to the neutralizing responses in these patients.
HIV 特异性广泛中和抗体 (bnAbs) 已从高病毒血症患者中分离出来，但也从抑制 HIV-1 复制的 HIV 控制器中分离出来。在这些精英控制器 (ECs) 中，多种参数有助于病毒抑制，包括遗传因素和免疫反应。定义与 bnAbs 产生相关的免疫相关性可能有助于设计有效的免疫疗法。在这项研究中，在 HLA-B57 保护性等位基因阳性或阴性的 ECs 中，在接受治疗的 HIV 感染和 HIV 阴性个体中，我们使用流式细胞术和 ELISPOT 对记忆 B 细胞区室和 HIV 特异性记忆 B 细胞反应进行了表征。ECs 保留了其记忆 B 细胞区室，与接受治疗的患者相比，维持了可检测到的 HIV 特异性记忆 B 细胞反应。所有 ECs 均存在 IgG1+ HIV 特异性记忆 B 细胞，但有些个体也保留了 IgG2+ 或 IgG3+ 反应。重要的是，我们还分析了来自 ECs 的血清中和一组包括传播/原始病毒在内的 HIV 株的能力。分别有 29%和 21%的 HLA-B57+和 HLA-B57-ECs 中和了至少 40%的测试病毒株。值得注意的是，在 HLA-B57+ECs 中，HIV-Env 特异性记忆 B 细胞的频率与中和广度呈正相关，这表明 HIV 特异性记忆 B 细胞的保留可能有助于这些患者的中和反应。
