可溶性和病毒SARS-CoV-2尖端蛋白的不一致的抗原特性
Sameer Kumar1, Souradip Dasgupta1, Mohammad M Sajadi1,2,3
1Division of Vaccine Research, Institute of Human Virology, University of Maryland School of Medicine, 725 West Lombard Street, Baltimore, MD 21201, USA.
Viruses
|March 28, 2024
概括
开发SARS-CoV-2疫苗需要了解尖端蛋白结构. 这项研究揭示了工程尖端修剪器和病毒相关尖端蛋白具有不同的抗原性,影响抗体结合和疫苗设计策略.
科学领域:
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
- 生物化学 生物化学
背景情况:
- 开发针对SARS-CoV-2的有效疫苗和免疫疗法需要准三基尖 (S) 蛋白.
- 目前的策略通常使用可溶性,稳定型三元体作为构造物,但它们的抗原性可能与原生维龙S蛋白不同.
- 以前的研究表明,可溶性S蛋白替代物与实际的SARS-CoV-2病毒之间抗体结合的差异.
研究的目的:
- 研究人类单克隆抗体 (mAbs) 对不同形式的SARS-CoV-2尖端蛋白的反应性.
- 为了比较抗S和抗甘氨酸mAbs与可溶性trimers,伪病毒和非活化的病毒的结合效率.
- 评估这些发现对设计未来SARS-CoV-2抗病毒策略的影响.
主要方法:
- 在生理学相关条件下使用单分子光相关谱学 (FCS).
- 评估mAbs的结合效率,使用可溶性S剪切剂,伪病毒和非活化的野生型SARS-CoV-2病毒.
- 测试了广泛中和和非中和的抗S mAbs,以及抗糖mAbs.
主要成果:
- 抗S和抗甘氨酸mAbs都显示出可变但高效的结合于稳定可溶性trimers.
- 溶性S结合效率与对非活化病毒的反应性正相关,但与伪病毒无关.
- 中和抗体强度与任何测试目标的结合效率无关;抗甘氨酸抗体没有显示中和活性.
结论:
- 维里昂表面显示了功能和非功能修剪剂的混合,中和抗体有利于功能性抗体.
- 洗剂释放的维S与抗甘氨酸抗体的反应性增加,但与抗S mAbs的反应性降低.
- 工程化可溶性修剪剂表现出对两种抗体类型反应的复合结构,突出显示了在疫苗设计中需要单个病毒分析的必要性.
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