使用SARS-CoV-2尖峰和SARS-CoV核囊的联合免疫保护K18-hACE2小鼠,但增加了肺病理
Jaekwan Kim1, Alla Kachko1, Prabhuanand Selvaraj1
1Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
NPJ vaccines
|February 13, 2025
概括
结合SARS-CoV-2尖峰和核囊蛋白的下一代疫苗提供了保护. 然而,使用一种变异性核囊抗原可能会增加肺病理,尽管病毒控制.
科学领域:
- 免疫学 免疫学 免疫学
- 疫苗学 疫苗学 疫苗学
- 病毒学 病毒学
背景情况:
- 目前的SARS-CoV-2疫苗针对的是尖端蛋白,但变种降低了它们的有效性.
- 核囊蛋白在SARS-CoV-2变种中保存,是T细胞免疫的潜在目标.
- 之前对SARS-CoV的研究表明,核囊免疫可能会增强疾病.
研究的目的:
- 评估结合SARS-CoV-2尖端和核囊蛋白的下一代疫苗的安全性和有效性.
- 为了比较免疫反应和使用SARS-CoV核体 (N1) 与SARS-CoV-2核体 (N2) 的疫苗所赋予的保护.
- 在小鼠模型中评估核囊免疫对疾病增强的影响.
主要方法:
- 使用K18-hACE2小鼠模型进行SARS-CoV-2感染研究.
- 接种了SARS-CoV变体核囊 (N1) 的免疫小鼠,单独使用或使用SARS-CoV-2尖端蛋白.
- 基于N1的疫苗与含有SARS-CoV-2核体 (N2) 和尖端蛋白的疫苗进行了比较.
- 评估了肺部和大脑的保护,肺部病理,以及T和B细胞在挑战前和之后的反应.
主要成果:
- 与对照组相比,尖核囊疫苗保护了肺和大脑免受SARS-CoV-2的感染,并减少了肺病理.
- 用N1 (单独或与尖端) 免疫的小鼠在挑战前显示出更高的T和B细胞反应.
- 与尖峰免疫或N2免疫相比,N1免疫导致肺病理增加.
- 在N1免疫组中观察到病毒控制,但高肺病理的权衡.
结论:
- 尖核囊疫苗是安全有效的,即使有不同的核囊序列.
- 在这个模型中,核囊抗原的免疫性可以导致肺部病理增加,尽管它能够控制病毒.
- 未来的疫苗开发应该考虑免疫主导性和与核囊抗原相关的增强病理的可能性.
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