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辅助组合和抗原多元化形状中和抗体和T细胞对SARS-CoV-2 RBD亚单元疫苗的反应

João Pedro da Silva Nunes¹, Mariângela de Oliveira Silva², Juliana de Souza Apostolico¹

¹Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo-Escola Paulista de Medicina (UNIFESP/EPM), São Paulo, Brazil.

Frontiers in immunology

|August 1, 2025

概括

优化COVID-19疫苗,多元化受体结合域 (RBD) 抗原与特定辅助剂相结合,显著增强了免疫反应和对SARS-CoV-2变种的更广泛的中和.

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:

COVID-19疫苗开发面临不平等和新出现的SARS-CoV-2令人担忧的变种 (VOC) 的挑战.
尖端蛋白的受体结合域 (RBD) 是中和抗体的关键目标,也是子单位疫苗的有希望的抗原.
提高RBD免疫性需要使用抗原多元化和辅助剂添加等策略.

研究的目的:

为了比较武汉RBD单体,同型和异型三聚体 (Delta,Beta,Gamma变体) 的免疫性质.
选辅助剂以优化针对SARS-CoV-2的幽默和细胞免疫力.
为了确定诱导T细胞反应的特定RBD表位.

主要方法:

用RBD单体,二元体和三元体配方免疫小鼠.
选辅助剂,包括AddaS03和Poly I:C,单独和组合.
评估幽默免疫 (抗体反应,中和) 和细胞免疫 (T细胞反应,细胞因子产生).
在挑战后的小鼠肺部病毒复制的分析.

主要成果:

带有AddaS03辅助剂的RBD二元和三元配方诱导了更高的幽默反应和更广泛的中和.
在小鼠中,RBD-trimer免疫显示出更有效的病毒复制抑制.
AddaS03和Poly I:C辅助剂的组合显示出协同效应,增强抗体亲和力并产生长寿命的血细胞.
特定的RBD被确定为免疫主导的CD4 (12),CD8 (28,29) T细胞表位.

结论:

抗原多元化,特别是使用trimers,显著提高疫苗免疫性.
辅助剂的战略组合,如AddaS03和Poly I:C,可以协同增强幽默和细胞免疫力.
已识别的T细胞表位为开发下一代SARS-CoV-2疫苗提供了目标.

关键词:

在RBD中,RBD是RBD.这就是SARS-CoV-2病毒.一个辅助的辅助者.重组蛋白质蛋白质的重组蛋白质是什么?疫苗疫苗疫苗疫苗

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