Boesch Austin W, Osei-Owusu Nana Yaw, Crowley Andrew R, Chu Thach H, Chan Ying N, Weiner Joshua A, Bharadwaj Pranay, Hards Rufus, Adamo Mark E, Gerber Scott A, Cocklin Sarah L, Schmitz Joern E, Miles Adam R, Eckman Joshua W, Belli Aaron J, Reimann Keith A, Ackerman Margaret E
Thayer School of Engineering, Dartmouth College , Hanover, NH , USA.
Molecular and Cellular Biology Program, Dartmouth College , Hanover, NH , USA.
Front Immunol. 2016 Dec 13;7:589. doi: 10.3389/fimmu.2016.00589. eCollection 2016.
Antibodies raised in Indian rhesus macaques [ (MM)] in many preclinical vaccine studies are often evaluated for titer, antigen-recognition breadth, neutralization potency, and/or effector function, and for potential associations with protection. However, despite reliance on this key animal model in translation of promising candidate vaccines for evaluation in first in man studies, little is known about the properties of MM immunoglobulin G (IgG) subclasses and how they may compare to human IgG subclasses. Here, we evaluate the binding of MM IgG1, IgG2, IgG3, and IgG4 to human Fc gamma receptors (FcγR) and their ability to elicit the effector functions of human FcγR-bearing cells, and unlike in humans, find a notable absence of subclasses with dramatically silent Fc regions. Biophysical, , and characterization revealed MM IgG1 exhibited the greatest effector function activity followed by IgG2 and then IgG3/4. These findings in rhesus are in contrast with the canonical understanding that IgG1 and IgG3 dominate effector function in humans, indicating that subclass-switching profiles observed in rhesus studies may not strictly recapitulate those observed in human vaccine studies.
在许多临床前疫苗研究中，在印度恒河猴（MM）体内产生的抗体通常会针对效价、抗原识别广度、中和效力和/或效应功能，以及与保护作用的潜在关联进行评估。然而，尽管在将有前景的候选疫苗转化为人体首次研究评估时依赖这种关键动物模型，但对于MM免疫球蛋白G（IgG）亚类的特性以及它们与人类IgG亚类的比较情况却知之甚少。在此，我们评估了MM IgG1、IgG2、IgG3和IgG4与人类Fcγ受体（FcγR）的结合情况，以及它们引发携带人类FcγR细胞效应功能的能力，并且与人类不同的是，我们发现明显缺乏Fc区域显著沉默的亚类。生物物理、[此处原文缺失相关内容]和[此处原文缺失相关内容]表征显示，MM IgG1表现出最大的效应功能活性，其次是IgG2，然后是IgG3/4。恒河猴的这些发现与IgG1和IgG3在人类中主导效应功能的传统认知形成对比，表明在恒河猴研究中观察到的亚类转换情况可能无法严格重现人类疫苗研究中观察到的情况。
