STING and TLR9 agonists synergistically enhance the immunogenicity of SARS-CoV-2 subunit vaccine  

作　　者：Yang Li Ziwei Chen Xinyi Lu Jiufeng Sun Mengyu Guo Huige Zhou Ru Bai Yuliang Zhao Chunying Chen Yaling Wang 

机构地区：[1]CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience,National Center for Nanoscience and Technology,Beijing 100190,China [2]University of Chinese Academy of Sciences,Beijing 100049,China [3]The GBA National Institute for Nanotechnology Innovation,Guangzhou 510700,China [4]Guangdong Provincial Institute of Public Health,Guangdong Provincial Center for Disease Control and Prevention,Guangzhou 511430,China [5]Research Unit of Nanoscience and Technology,Chinese Academy of Medical Sciences,Beijing 100049,China

出　　处：《Nano Research》2023年第12期13322-13334,共13页纳米研究（英文版）

基　　金：supported by the National Basic Research Program of China(Nos.2022YFA1603701 and 2021YFA1200900);Strategic Priority Research Program of Chinese Academy of Sciences(No.XDB36000000);the National Natural Science Foundation of China(Nos.82341044 and 22027810);CAMS Innovation Fund for Medical Sciences(No.CIFMS 2019-I2M-5-018).

摘　　要：Vaccines that are reliable and efficacious are essential in the fight against the COVID-19 pandemic.In this study,we designed a dual-adjuvant system with two pathogen-associated molecular patterns(PAMPs),MnOx and CpG.This system can improve the retention of antigens at the injection site,facilitate pro-inflammatory cytokines secretion,further recruit and activate dendritic cells(DCs).As a result,antigens can be delivered to lymph nodes specifically,and adaptive immunity was strengthened.The immunized group showed an enhanced and broadened humoral and cellular immune response in systemic immunity and lung protection when combined with a tandem repeat-linked dimeric antigen version of the SARS-CoV-2 receptor binding domain(RBDdimer).Remarkably,even with a significant reduction in antigen dosage(three times lower)and a decrease in injection frequencies,our nanovaccine was able to produce the highest neutralizing antibody titers against various mutants.These titers were four-fold higher for the wild-type strain and two-fold higher for both the Beta and Omicron variants in comparison with those elicited by the Alum adjuvant group.In conclusion,our dual-adjuvant formulation presents a promising protein subunit-based candidate vaccine against SARS-CoV-2.

关 键 词：dual-adjuvant system synergistic immune activation antigen dosage reducing variants neutralizing 

分 类 号：R563.1[医药卫生—呼吸系统] R392[医药卫生—内科学]