Roslyn A Taylor, Sixia Xiao, Ann M Carias, Michael D McRaven, Divya N Thakkar, Mariluz Araínga, Ramon Lorenzo-Redondo, Edward J Allen, Kenneth A Rogers, Sidath C Kumarapperuma, Siqi Gong, Meegan R Anderson, Yanique Thomas, Patrick J Madden, Davide Corti, Elisabetta Cameroni, Antonio Lanzavecchia, Beth Goins, Peter Fox, Francois J Villinger, Ruth M Ruprecht, Thomas J Hope
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We combined Positron Emission Tomography imaging and fluorescent microscopy of <sup>64</sup>Cu-labeled, photoactivatable-green fluorescent protein HIV (PA-GFP-BaL) and fluorescently labeled HGN194 IgG1 to determine whether intravenously instilled IgG influences viral interaction with mucosal barriers and viral penetration in colorectal tissue 2 h after rectal viral challenge. Our results show that IgG1 did not alter the number of virions found throughout the colon or viral penetration into the epithelium of the rectum or descending colon. A minor increase in virions was observed in the transverse colon of IgG1 treated animals. Overall, the number of viral particles found in the mesenteric lymph nodes was low. However, IgG1 administration resulted in a significant reduction of virions found in mesenteric lymph nodes. 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引用次数: 0
摘要
中和单克隆抗体在预防人类免疫缺陷病毒(HIV)感染方面具有巨大潜力。IgG 是人类血清中含量最高的抗体,半衰期长,具有强大的效应功能,因此是预防 HIV 治疗的首选。我们结合正电子发射断层扫描(PET)成像和荧光显微镜观察 64Cu 标记的光活化-GFP HIV(PA-GFP-BaL)和荧光标记的 HGN194 IgG1,以确定静脉注射 IgG 是否会影响病毒与粘膜屏障的相互作用以及直肠病毒挑战两小时后病毒在结肠直肠组织中的穿透。我们的研究结果表明,IgG1 不会改变整个结肠中发现的病毒数量,也不会改变病毒对直肠或降结肠上皮的穿透。经 IgG1 处理的动物横结肠中的病毒数量略有增加。总体而言,在肠系膜淋巴结中发现的病毒颗粒数量较少。然而,IgG1 的施用导致肠系膜淋巴结中发现的病毒颗粒显著减少。综上所述,我们的研究结果表明,HGN194 IgG1 并不能阻止病毒穿透结肠直肠粘膜,但可能会干扰 HIV 病毒进入淋巴系统。
PET/CT Targeted Tissue Sampling Reveals Intravenously Administered HGN194 IgG1 Affects HIV Distribution after Rectal Exposure.
Neutralizing monoclonal antibodies hold great potential for prevention of human immunodeficiency virus (HIV) acquisition. IgG is the most abundant antibody in human serum, has a long half-life, and potent effector functions, making it a prime candidate for an HIV prevention therapeutic. We combined Positron Emission Tomography imaging and fluorescent microscopy of 64Cu-labeled, photoactivatable-green fluorescent protein HIV (PA-GFP-BaL) and fluorescently labeled HGN194 IgG1 to determine whether intravenously instilled IgG influences viral interaction with mucosal barriers and viral penetration in colorectal tissue 2 h after rectal viral challenge. Our results show that IgG1 did not alter the number of virions found throughout the colon or viral penetration into the epithelium of the rectum or descending colon. A minor increase in virions was observed in the transverse colon of IgG1 treated animals. Overall, the number of viral particles found in the mesenteric lymph nodes was low. However, IgG1 administration resulted in a significant reduction of virions found in mesenteric lymph nodes. Taken together, our results show that HGN194 IgG1 does not prevent virions from penetrating into the colorectal mucosa but may perturb HIV virion access to the lymphatic system.
期刊介绍:
AIDS Research and Human Retroviruses was the very first AIDS publication in the field over 30 years ago, and today it is still the critical resource advancing research in retroviruses, including AIDS. The Journal provides the broadest coverage from molecular biology to clinical studies and outcomes research, focusing on developments in prevention science, novel therapeutics, and immune-restorative approaches. Cutting-edge papers on the latest progress and research advances through clinical trials and examination of targeted antiretroviral agents lead to improvements in translational medicine for optimal treatment outcomes.
AIDS Research and Human Retroviruses coverage includes:
HIV cure research
HIV prevention science
- Vaccine research
- Systemic and Topical PreP
Molecular and cell biology of HIV and SIV
Developments in HIV pathogenesis and comorbidities
Molecular biology, immunology, and epidemiology of HTLV
Pharmacology of HIV therapy
Social and behavioral science
Rapid publication of emerging sequence information.