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Detection of SARS-CoV-2 Neutralizing Antibodies using High-Throughput Fluorescent Imaging of Pseudovirus Infection

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保护性非中和性抗N终端域mAb 保持Fc介导功能,对抗高达BA.2.86-JN.1的SARS-COV-2变种,因减弱病毒力而对JN.1进行多余的体内保护

Arman Izadi¹, Magdalena Godzwon², Anna Söderlund Strand³

¹Department of Clinical Sciences Lund, Division of Infection Medicine, Faculty of Medicine, Lund University, Lund, Sweden.

Journal of immunology (Baltimore, Md. : 1950)

|July 17, 2024

概括

针对SARS-CoV-2尖端蛋白变体的两个非中和抗体保留了对Omicron亚变体的功能. 然而,一个抗体对BA.2.86失去了有效性,而另一个抗体则对不那么致命的JN.1菌株产生了保护作用.

科学领域:

免疫学免疫学免疫学
病毒学病毒学
传染性疾病传染性疾病

背景情况:

抗尖峰抗体的fc介导的效应因子功能对于对SARS-CoV-2的保护至关重要.
此前已确定的非中和性,声单克隆抗体 (mAbs) Ab81 (准受体结合域) 和 Ab94 (准N终端域) 在K18-hACE2小鼠中证明了对致命的武汉SARS-CoV-2的保护.

研究的目的:

调查非中和mAbs (Ab81和Ab94) 针对演变的SARS-CoV-2变种的功能和结合能力.
评估这些mAbs对Omicron及其子系的Fc介导功能和抗原结合.
在小鼠模型中评估Ab94与JN.1变异的体内疗效.

主要方法:

评估了mAbs Ab81和Ab94对各种SARS-CoV-2变体的抗原结合亲和力和Fc介导的效应因子功能,包括Omicron亚系.
使用K18-hACE2小鼠模型进行体内疗效研究,用严格剂量的SARS-CoV-2变种进行注射.
采用临床评分系统来评估治疗与对照组的疾病表现和保护.

主要成果:

Ab81和Ab94保持了纳米分子亲和力和Fc介导的功能,可以对抗Omicron和子变种 (BA.2,BA.4,BA.5,XBB,XBB1.5,BQ1.1).
Ab81对严重突变的BA.2.86失去了功能,而Ab94仍然具有功能.
在体内研究中,使用Ab94对抗JN.1在对照小鼠中显示出较低的疾病表现,但接受Ab94治疗的小鼠表现出更好的保护,表明保留了Fc介导的益处.
在K18-hACE2模型中,与之前的SARS-CoV-2菌株相比,JN.1在体内毒性显著降低.

结论:

非中和抗受体结合域mAb (Ab81) 对BA.2.86失去反应性,突出突变对抗体功能的影响.
反N终端域mAb (Ab94) 与测试的变体相比保留了功能,这表明可能有更广泛的覆盖范围.
非中和抗体的Fc介导功能仍然是有益的,即使对像JN.1这样的不那么致命的SARS-CoV-2菌株也是如此.
SARS-CoV-2 的演变会影响抗体的有效性,这强调了需要持续监测和开发广泛的保护性治疗方法的需要.

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