Grobben Marloes, Bakker Margreet, Schriek Angela I, Levels Liesbeth J J, Umotoy Jeffrey C, Tejjani Khadija, van Breemen Mariëlle J, Lin Ryan N, de Taeye Steven W, Ozorowski Gabriel, Kootstra Neeltje A, Ward Andrew B, Kent Stephen J, Hogarth P Mark, Wines Bruce D, Sanders Rogier W, Chung Amy W, van Gils Marit J
Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Amsterdam, The Netherlands.
Amsterdam Institute for Immunology and Infectious Diseases, Amsterdam, The Netherlands.
PLoS Pathog. 2024 Dec 11;20(12):e1012739. doi: 10.1371/journal.ppat.1012739. eCollection 2024 Dec.
HIV-1 infection leads to chronic disease requiring life-long treatment and therefore alternative therapeutics, a cure and/or a protective vaccine are needed. Antibody-mediated effector functions could have a role in the fight against HIV-1. However, the properties underlying the potential beneficial effects of antibodies during HIV-1 infection are poorly understood. To identify a specific profile of antibody features associated with delayed disease progression, we studied antibody polyfunctionality during untreated HIV-1 infection in the well-documented Amsterdam Cohort Studies. Serum samples were analyzed from untreated individuals with HIV-1 at approximately 6 months (n = 166) and 3 years (n = 382) post-seroconversion (post-SC). A Luminex antibody Fc array was used to profile 15 different Fc features for serum antibodies against 20 different HIV-1 envelope glycoprotein antigens and the resulting data was also compared with data on neutralization breadth. We found that high HIV-1 specific IgG1 levels and low IgG2 and IgG4 levels at 3 years post-SC were associated with delayed disease progression. Moreover, delayed disease progression was associated with a broad and polyfunctional antibody response. Specifically, the capacity to interact with all Fc γ receptors (FcγRs) and C1q, and in particular with FcγRIIa, correlated positively with delayed disease progression. There were strong correlations between antibody Fc features and neutralization breadth and several antibody features that were associated with delayed disease progression were also associated with the development of broad and potent antibody neutralization. In summary, we identified a strong association between broad, polyfunctional antibodies and delayed disease progression. These findings contribute new information for the fight against HIV-1, especially for new antibody-based therapy and cure strategies.
HIV-1感染会导致慢性疾病，需要终身治疗，因此需要替代疗法、治愈方法和/或保护性疫苗。抗体介导的效应功能可能在对抗HIV-1中发挥作用。然而，人们对HIV-1感染期间抗体潜在有益作用的基础特性了解甚少。为了确定与疾病进展延迟相关的抗体特征的特定概况，我们在记录完备的阿姆斯特丹队列研究中，研究了未经治疗的HIV-1感染期间抗体的多功能性。分析了血清转化后约6个月（n = 166）和3年（n = 382）时未经治疗的HIV-1感染者的血清样本。使用Luminex抗体Fc阵列分析针对20种不同HIV-1包膜糖蛋白抗原的血清抗体的15种不同Fc特征，并将所得数据与中和广度数据进行比较。我们发现，血清转化后3年时高HIV-1特异性IgG1水平以及低IgG2和IgG4水平与疾病进展延迟相关。此外，疾病进展延迟与广泛且多功能的抗体反应相关。具体而言，与所有Fcγ受体（FcγRs）和C1q相互作用的能力，特别是与FcγRIIa相互作用的能力，与疾病进展延迟呈正相关。抗体Fc特征与中和广度之间存在很强的相关性，并且一些与疾病进展延迟相关的抗体特征也与广泛而有效的抗体中和作用的发展相关。总之，我们确定了广泛的多功能抗体与疾病进展延迟之间存在很强的关联。这些发现为对抗HIV-1的斗争提供了新信息，特别是对于基于抗体的新治疗方法和治愈策略。
