First-in-human immunoPET imaging of HIV-1 infection using (89)Zr-labeled VRC01 broadly neutralizing antibody.
First-in-human immunoPET imaging of HIV-1 infection using (89)Zr-labeled VRC01 broadly neutralizing antibody.
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DOI：
10.1038/s41467-022-28727-5
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发表时间：
2022-03-09
影响因子：
16.6
通讯作者：
Henrich TJ
中科院分区：
文献类型：
--
作者：
Beckford-Vera DR;Flavell RR;Seo Y;Martinez-Ortiz E;Aslam M;Thanh C;Fehrman E;Pardons M;Kumar S;Deitchman AN;Ravanfar V;Schulte B;Wu IK;Pan T;Reeves JD;Nixon CC;Iyer NS;Torres L;Munter SE;Hyunh T;Petropoulos CJ;Hoh R;Franc BL;Gama L;Koup RA;Mascola JR;Chomont N;Deeks SG;VanBrocklin HF;Henrich TJ
实现HIV感染的长期抗逆转录病毒（ART）免费缓解或功能性治愈的主要障碍是存在建立长寿病毒库的持续感染细胞。然而，艾滋病毒主要存在于常规采样无法到达的解剖区域，迫切需要非侵入性方法来了解艾滋病毒持久性的纵向组织范围内的负担。正电子发射断层扫描（PET）成像是一种很有前途的战略，以确定和表征的组织范围内的艾滋病毒的负担。在这里，我们评估了使用免疫PET成像来表征HIV储库的有效性，并使用放射性标记的HIV Env特异性广泛中和抗体89 Zr-VRC 01在具有可检测的病毒血症和抑制性ART的HIV感染个体中与未感染对照相比识别持续病毒转录活性的解剖学病灶（NCT 03729752）。我们还评估了PET示踪剂在组织中的摄取和ART启动时间之间的关系，以及从淋巴结活检获得的CD 4 T细胞中的直接HIV蛋白表达。我们观察到与未感染的对照组（N = 5）相比，在具有可检测的病毒血症的HIV感染个体（N = 5）和抑制性ART（N = 5）中，各种组织（包括淋巴结和肠道）中的89 Zr-VRC 01摄取显著增加。重要的是，病毒血症和ART抑制参与者腹股沟淋巴结中的PET示踪剂摄取与组织中直接测量的HIV蛋白表达显著正相关。我们的策略可以允许残留的HIV感染的非侵入性纵向表征，并奠定了框架，在各种其他感染性疾病的免疫PET成像的发展。在这里，作者应用正电子发射断层扫描（PET）成像，使用放射性标记的广泛中和抗体89 Zr-VRC 01可视化感染个体的HIV组织范围负荷，并显示PET示踪剂淋巴结摄取与直接从这些组织获得的细胞中测量的HIV蛋白水平呈正相关。这种策略可以允许在治疗干预的设置中对残留的HIV感染进行非侵入性表征。
A major obstacle to achieving long-term antiretroviral (ART) free remission or functional cure of HIV infection is the presence of persistently infected cells that establish a long-lived viral reservoir. HIV largely resides in anatomical regions that are inaccessible to routine sampling, however, and non-invasive methods to understand the longitudinal tissue-wide burden of HIV persistence are urgently needed. Positron emission tomography (PET) imaging is a promising strategy to identify and characterize the tissue-wide burden of HIV. Here, we assess the efficacy of using immunoPET imaging to characterize HIV reservoirs and identify anatomical foci of persistent viral transcriptional activity using a radiolabeled HIV Env-specific broadly neutralizing antibody, 89Zr-VRC01, in HIV-infected individuals with detectable viremia and on suppressive ART compared to uninfected controls (NCT03729752). We also assess the relationship between PET tracer uptake in tissues and timing of ART initiation and direct HIV protein expression in CD4 T cells obtained from lymph node biopsies. We observe significant increases in 89Zr-VRC01 uptake in various tissues (including lymph nodes and gut) in HIV-infected individuals with detectable viremia (N = 5) and on suppressive ART (N = 5) compared to uninfected controls (N = 5). Importantly, PET tracer uptake in inguinal lymph nodes in viremic and ART-suppressed participants significantly and positively correlates with HIV protein expression measured directly in tissue. Our strategy may allow non-invasive longitudinal characterization of residual HIV infection and lays the framework for the development of immunoPET imaging in a variety of other infectious diseases. Here, the authors apply positron emission tomography (PET) imaging to visualize HIV tissue-wide burden in infected individuals using a radiolabeled broadly neutralizing antibody, 89Zr-VRC01, and show that PET tracer lymph node uptake positively correlates with HIV protein levels measured directly from cells obtained from these tissues. This strategy may allow non-invasive characterization of residual HIV infection in the setting of therapeutic interventions.
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DOI：
10.1007/s00259-019-04307-6
发表时间：
2019-07-01
影响因子：
9.1
作者：
Hofheinz, Frank;Li, Yimin;Zschaeck, Sebastian
通讯作者：
Zschaeck, Sebastian
影响因子：
6.4
作者：
Henrich, Timothy J.;Hanhauser, Emily;Kuritzkes, Daniel R.
通讯作者：
Kuritzkes, Daniel R.
影响因子：
9.3
作者：
Hofheinz, Frank;Apostolova, Ivayla;van den Hoff, Joerg
通讯作者：
van den Hoff, Joerg
影响因子：
9.3
作者：
Jauw, Yvonne W. S.;O'Donoghue, Joseph A.;Huisman, Marc C.
通讯作者：
Huisman, Marc C.
DOI：
10.1016/j.str.2015.07.020
发表时间：
2015-10-06
期刊：
Structure (London, England : 1993)
影响因子：
--
作者：
Lee JH;de Val N;Lyumkis D;Ward AB
通讯作者：
Ward AB