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Nano Research 2023, 16(12): 13322-13334 https://doi.org/10.1007/s12274-023-6295-5
Research Article | Issue | Published: 02 December 2023

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

Show Author's Information Yang Li1,2,§,  Ziwei Chen1,2,§,  Xinyi Lu1,2,  Jiufeng Sun4,  Mengyu Guo1,  Huige Zhou1,  Ru Bai1,  Yuliang Zhao1,2,3,5,  Chunying Chen1,2,5( ),  Yaling Wang1,2( )
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
University of Chinese Academy of Sciences, Beijing 100049, China
The GBA National Institute for Nanotechnology Innovation, Guangzhou 510700, China
Guangdong Provincial Institute of Public Health, Guangdong Provincial Center for Disease Control and Prevention, Guangzhou 511430, China
Research Unit of Nanoscience and Technology, Chinese Academy of Medical Sciences, Beijing 100049, China

§ Yang Li and Ziwei Chen contributed equally to this work.

Keywords:
synergistic immune activation, dual-adjuvant system, antigen dosage reducing, variants neutralizing
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Nanobiotechnology
Cite this article:
Li Y, Chen Z, Lu X, et al. STING and TLR9 agonists synergistically enhance the immunogenicity of SARS-CoV-2 subunit vaccine. Nano Research, 2023, 16(12): 13322-13334. https://doi.org/10.1007/s12274-023-6295-5
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Abstract Full text Electronic supplementary material About this article

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.


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Abstract
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Electronic supplementary material
About this article

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

Show Author's information Yang Li1,2,§, Ziwei Chen1,2,§, Xinyi Lu1,2, Jiufeng Sun4, Mengyu Guo1, Huige Zhou1, Ru Bai1, Yuliang Zhao1,2,3,5, Chunying Chen1,2,5( ), Yaling Wang1,2( )
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
University of Chinese Academy of Sciences, Beijing 100049, China
The GBA National Institute for Nanotechnology Innovation, Guangzhou 510700, China
Guangdong Provincial Institute of Public Health, Guangdong Provincial Center for Disease Control and Prevention, Guangzhou 511430, China
Research Unit of Nanoscience and Technology, Chinese Academy of Medical Sciences, Beijing 100049, China

§ Yang Li and Ziwei Chen contributed equally to this work.

Abstract

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.

Keywords: synergistic immune activation, dual-adjuvant system, antigen dosage reducing, variants neutralizing

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Publication history
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Acknowledgements

Publication history

Received: 02 August 2023
Revised: 25 October 2023
Accepted: 30 October 2023
Published: 02 December 2023
Issue date: December 2023

Copyright

© Tsinghua University Press 2023

Acknowledgements

Acknowledgements

This work was 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), and CAMS Innovation Fund for Medical Sciences (No. CIFMS 2019-I2M-5-018).

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