Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Cell Rep. 2023 Dec 26;42(12):113450. doi: 10.1016/j.celrep.2023.113450. Epub 2023 Nov 28.
HIV gp120 engineered outer domain germline-targeting version 8 (eOD-GT8) was designed specifically to engage naive B cell precursors of VRC01-class antibodies. However, the frequency and affinity of naive B cell precursors able to recognize eOD-GT8 have been evaluated only in U.S. populations. HIV infection is disproportionally concentrated in sub-Saharan Africa, so we seek to characterize naive B cells able to recognize eOD-GT8 in sub-Saharan cohorts. We demonstrate that people from sub-Saharan Africa have a higher or equivalent frequency of naive B cells able to engage eOD-GT8 compared with people from the U.S. Genetically, the higher frequency of eOD-GT8-positive cells is accompanied by a higher level of naive B cells with gene signatures characteristic of the VRC01 class, as well as other CD4bs-directed antibodies. Our study demonstrates that vaccination with eOD-GT8 in sub-Saharan Africa could be successful at expanding and establishing a pool of CD4bs-directed memory B cells from naive precursors.
HIV gp120 工程外域种系靶向版本 8（eOD-GT8）专门设计用于与 VRC01 类抗体的原始 B 细胞前体结合。然而，能够识别 eOD-GT8 的原始 B 细胞前体的频率和亲和力仅在美国人群中进行了评估。艾滋病毒感染在撒哈拉以南非洲不成比例地集中，因此我们试图描述能够识别 eOD-GT8 的原始 B 细胞在撒哈拉以南人群中的特征。我们证明，与来自美国的人相比，来自撒哈拉以南非洲的人能够与 eOD-GT8 结合的原始 B 细胞的频率更高或相当。从遗传学上讲，eOD-GT8 阳性细胞的高频率伴随着高水平的原始 B 细胞，这些细胞具有 VRC01 类以及其他 CD4bs 定向抗体的特征性基因特征。我们的研究表明，在撒哈拉以南非洲地区接种 eOD-GT8 可以成功地从原始前体中扩增和建立 CD4bs 定向记忆 B 细胞池。
