Decoupling HIV-1 antiretroviral drug inhibition from plasma antibody activity to evaluate broadly neutralizing antibody therapeutics and vaccines.

IF 11.7 1区 医学 Q1 CELL BIOLOGY
Cell Reports Medicine Pub Date : 2024-09-17 Epub Date: 2024-08-30 DOI:10.1016/j.xcrm.2024.101702
Magdalena Schwarzmüller, Cristina Lozano, Merle Schanz, Irene A Abela, Silvan Grosse-Holz, Selina Epp, Martina Curcio, Jule Greshake, Peter Rusert, Michael Huber, Roger D Kouyos, Huldrych F Günthard, Alexandra Trkola
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Abstract

The development of broadly neutralizing antibody (bnAb)-based therapeutic HIV-1 vaccines and cure concepts depends on monitoring bnAb plasma activity in people with HIV (PWH) on suppressive antiretroviral therapy (ART). To enable this, analytical strategies must be defined to reliably distinguish antibody-based neutralization from drug inhibition. Here, we explore strategies that either utilize drug-resistant viruses or remove drugs from plasma. We develop ART-DEX (ART dissociation and size exclusion), an approach which quantitatively separates drugs from plasma proteins following pH-triggered release allowing accurate definition of antibody-based neutralization. We demonstrate that ART-DEX, alone or combined with ART-resistant viruses, provides a highly effective and scalable means of assessing antibody neutralization during ART. Implementation of ART-DEX in standard neutralization protocols should be considered to enhance the analytical capabilities of studies evaluating bnAb therapeutics and therapeutic vaccines, furthering the development of advanced ART and HIV-1 cure strategies.

Abstract Image

将 HIV-1 抗逆转录病毒药物抑制与血浆抗体活性解耦,以评估广谱中和抗体疗法和疫苗。
基于广谱中和抗体 (bnAb) 的治疗性 HIV-1 疫苗和治愈概念的开发取决于对接受抑制性抗逆转录病毒疗法 (ART) 的 HIV 感染者 (PWH) 的 bnAb 血浆活性的监测。为此,必须确定分析策略,以可靠地区分抗体中和与药物抑制。在此,我们探讨了利用抗药性病毒或从血浆中去除药物的策略。我们开发了 ART-DEX(ART 解离和大小排阻),这种方法能在 pH 触发释放后定量地将药物从血浆蛋白中分离出来,从而准确地定义抗体中和。我们证明,ART-DEX 可单独或与抗逆转录病毒结合使用,为评估抗逆转录病毒疗法期间的抗体中和提供了一种高效、可扩展的方法。应考虑在标准中和方案中使用 ART-DEX,以提高 bnAb 治疗剂和治疗性疫苗评估研究的分析能力,促进先进抗逆转录病毒疗法和 HIV-1 治愈策略的发展。
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来源期刊
Cell Reports Medicine
Cell Reports Medicine Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)
CiteScore
15.00
自引率
1.40%
发文量
231
审稿时长
40 days
期刊介绍: Cell Reports Medicine is an esteemed open-access journal by Cell Press that publishes groundbreaking research in translational and clinical biomedical sciences, influencing human health and medicine. Our journal ensures wide visibility and accessibility, reaching scientists and clinicians across various medical disciplines. We publish original research that spans from intriguing human biology concepts to all aspects of clinical work. We encourage submissions that introduce innovative ideas, forging new paths in clinical research and practice. We also welcome studies that provide vital information, enhancing our understanding of current standards of care in diagnosis, treatment, and prognosis. This encompasses translational studies, clinical trials (including long-term follow-ups), genomics, biomarker discovery, and technological advancements that contribute to diagnostics, treatment, and healthcare. Additionally, studies based on vertebrate model organisms are within the scope of the journal, as long as they directly relate to human health and disease.
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