Department of Cell and Developmental Biology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
New Iberia Research Center, University of Louisiana at Lafayette, Lafayette, Louisiana, USA.
AIDS Res Hum Retroviruses. 2024 Nov;40(11):637-648. doi: 10.1089/AID.2024.0019. Epub 2024 Aug 28.
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 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. 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.
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 是人体血清中含量最丰富的抗体,半衰期长,具有强大的效应功能,使其成为 HIV 预防治疗的首选候选药物。我们结合正电子发射断层扫描成像和 Cu 标记的光活化绿色荧光蛋白 HIV(PA-GFP-BaL)的荧光显微镜以及荧光标记的 HGN194 IgG1,以确定静脉注射 IgG 是否会影响病毒与黏膜屏障的相互作用以及病毒在直肠病毒攻击后 2 小时内穿透结直肠组织。我们的结果表明,IgG1 并没有改变整个结肠中发现的病毒粒子的数量,也没有改变病毒穿透直肠或降结肠上皮的程度。在 IgG1 处理动物的横结肠中观察到病毒粒子略有增加。总的来说,肠系膜淋巴结中发现的病毒颗粒数量较少。然而,IgG1 的给药导致肠系膜淋巴结中发现的病毒粒子数量显著减少。总之,我们的结果表明 HGN194 IgG1 不能阻止病毒粒子穿透结直肠黏膜,但可能会干扰 HIV 病毒粒子进入淋巴系统。