马赛克RBD纳米颗粒在动物模型中可抵御不同的沙贝病毒感染
2022-08-08   阅读:684  

美国加州理工学院Pamela J. Bjorkman课题组发现,马赛克RBD纳米颗粒在动物模型中可抵御不同的沙贝病毒感染。相关论文于2022年8月5日发表于国际学术期刊《科学》。

为了对抗未来的严重急性呼吸道综合征冠状病毒2(SARS-CoV-2)变种和威胁全球健康的SARS样β-冠状病毒属(沙贝病毒)的溢出,研究人员设计了马赛克纳米颗粒,呈现随机排列的沙贝病毒病毒突刺受体结合域(RBD),用于激发针对保守和相对闭塞的表位的抗体,而不是可变、免疫优势和暴露的表位。研究人员比较了小鼠和猕猴由马赛克-8(SARS-CoV-2和七种动物沙贝病毒)和同型(仅SARS-CoV-2)RBD纳米颗粒引起的免疫反应,观察到马赛克-8对不匹配(不在纳米颗粒上)的毒株,包括SARS-CoV和动物沙贝病毒引起的反应更强烈。
 
马赛克-8免疫显示了对SARS-CoV-2变体(包括Omicron)的同等中和作用,并保护其免受SARS-CoV-2和SARS-CoV的挑战,而同型的SARS-CoV-2免疫仅保护其免受SARS-CoV-2的挑战。表位图显示,马赛克-8免疫后保守表位的靶向性增加。这些结果共同表明,马赛克-8 RBD纳米颗粒可以保护人们免受SARS-CoV-2变体和未来沙贝病毒的蔓延。
 
附:英文原文

Title: Mosaic RBD nanoparticles protect against challenge by diverse sarbecoviruses in animal models

Author: Alexander A. Cohen, Neeltje van Doremalen, Allison J. Greaney, Hanne Andersen, Ankur Sharma, Tyler N. Starr, Jennifer R. Keeffe, Chengcheng Fan, Jonathan E. Schulz, Priyanthi N. P. Gnanapragasam, Leesa M. Kakutani, Anthony P. WestJr., Greg Saturday, Yu E. Lee, Han Gao, Claudia A. Jette, Mark G. Lewis, Tiong K. Tan, Alain R. Townsend, Jesse D. Bloom, Vincent J. Munster, Pamela J. Bjorkman

Issue&Volume: 2022-07-05

Abstract: To combat future severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and spillovers of SARS-like betacoronaviruses (sarbecoviruses) threatening global health, we designed mosaic nanoparticles that present randomly arranged sarbecovirus spike receptor-binding domains (RBDs) to elicit antibodies against epitopes that are conserved and relatively occluded rather than variable, immunodominant, and exposed. We compared immune responses elicited by mosaic-8 (SARS-CoV-2 and seven animal sarbecoviruses) and homotypic (only SARS-CoV-2) RBD nanoparticles in mice and macaques and observed stronger responses elicited by mosaic-8 to mismatched (not on nanoparticles) strains, including SARS-CoV and animal sarbecoviruses. Mosaic-8 immunization showed equivalent neutralization of SARS-CoV-2 variants, including Omicrons, and protected from SARS-CoV-2 and SARS-CoV challenges, whereas homotypic SARS-CoV-2 immunization protected only from SARS-CoV-2 challenge. Epitope mapping demonstrated increased targeting of conserved epitopes after mosaic-8 immunization. Together, these results suggest that mosaic-8 RBD nanoparticles could protect against SARS-CoV-2 variants and future sarbecovirus spillovers.

DOI: abq0839

 

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