Cationic crosslinked carbon dots-adjuvanted intranasal vaccine induces protective immunity against Omicron-included SARS-CoV-2 variants
Abstract Mucosal immunity plays a significant role in the first-line defense against viruses transmitted and infected through the respiratory system, such as SARS-CoV-2. However, the lack of effective and safe adjuvants currently limits the development of COVID-19 mucosal vaccines. In the current st...
Main Authors: | , , , , , , , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Nature Portfolio
2023-05-01
|
Series: | Nature Communications |
Online Access: | https://doi.org/10.1038/s41467-023-38066-8 |
_version_ | 1827948048324493312 |
---|---|
author | Hong Lei Aqu Alu Jingyun Yang Xi He Cai He Wenyan Ren Zimin Chen Weiqi Hong Li Chen Xuemei He Li Yang Jiong Li Zhenling Wang Wei Wang Yuquan Wei Shuaiyao Lu Guangwen Lu Xiangrong Song Xiawei Wei |
author_facet | Hong Lei Aqu Alu Jingyun Yang Xi He Cai He Wenyan Ren Zimin Chen Weiqi Hong Li Chen Xuemei He Li Yang Jiong Li Zhenling Wang Wei Wang Yuquan Wei Shuaiyao Lu Guangwen Lu Xiangrong Song Xiawei Wei |
author_sort | Hong Lei |
collection | DOAJ |
description | Abstract Mucosal immunity plays a significant role in the first-line defense against viruses transmitted and infected through the respiratory system, such as SARS-CoV-2. However, the lack of effective and safe adjuvants currently limits the development of COVID-19 mucosal vaccines. In the current study, we prepare an intranasal vaccine containing cationic crosslinked carbon dots (CCD) and a SARS-CoV-2 antigen, RBD-HR with spontaneous antigen particlization. Intranasal immunization with CCD/RBD-HR induces high levels of antibodies with broad-spectrum neutralization against authentic viruses/pseudoviruses of Omicron-included variants and protects immunized female BALB/c mice from Omicron infection. Despite strong systemic cellular immune response stimulation, the intranasal CCD/RBD-HR vaccine also induces potent mucosal immunity as determined by the generation of tissue-resident T cells in the lungs and airway. Moreover, CCD/RBD-HR not only activates professional antigen-presenting cells (APCs), dendritic cells, but also effectively targets nasal epithelial cells, promotes antigen binding via sialic acid, and surprisingly provokes the antigen-presenting of nasal epithelial cells. We demonstrate that CCD is a promising intranasal vaccine adjuvant for provoking strong mucosal immunity and might be a candidate adjuvant for intranasal vaccine development for many types of infectious diseases, including COVID-19. |
first_indexed | 2024-04-09T12:48:16Z |
format | Article |
id | doaj.art-4c7a1a957b664368a7ddf9665976879b |
institution | Directory Open Access Journal |
issn | 2041-1723 |
language | English |
last_indexed | 2024-04-09T12:48:16Z |
publishDate | 2023-05-01 |
publisher | Nature Portfolio |
record_format | Article |
series | Nature Communications |
spelling | doaj.art-4c7a1a957b664368a7ddf9665976879b2023-05-14T11:21:58ZengNature PortfolioNature Communications2041-17232023-05-0114111710.1038/s41467-023-38066-8Cationic crosslinked carbon dots-adjuvanted intranasal vaccine induces protective immunity against Omicron-included SARS-CoV-2 variantsHong Lei0Aqu Alu1Jingyun Yang2Xi He3Cai He4Wenyan Ren5Zimin Chen6Weiqi Hong7Li Chen8Xuemei He9Li Yang10Jiong Li11Zhenling Wang12Wei Wang13Yuquan Wei14Shuaiyao Lu15Guangwen Lu16Xiangrong Song17Xiawei Wei18Laboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityLaboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityLaboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityLaboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityLaboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityLaboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityLaboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityLaboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityLaboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityLaboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityLaboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityLaboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityLaboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityLaboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityLaboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityNational Kunming High-level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeLaboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityLaboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityLaboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityAbstract Mucosal immunity plays a significant role in the first-line defense against viruses transmitted and infected through the respiratory system, such as SARS-CoV-2. However, the lack of effective and safe adjuvants currently limits the development of COVID-19 mucosal vaccines. In the current study, we prepare an intranasal vaccine containing cationic crosslinked carbon dots (CCD) and a SARS-CoV-2 antigen, RBD-HR with spontaneous antigen particlization. Intranasal immunization with CCD/RBD-HR induces high levels of antibodies with broad-spectrum neutralization against authentic viruses/pseudoviruses of Omicron-included variants and protects immunized female BALB/c mice from Omicron infection. Despite strong systemic cellular immune response stimulation, the intranasal CCD/RBD-HR vaccine also induces potent mucosal immunity as determined by the generation of tissue-resident T cells in the lungs and airway. Moreover, CCD/RBD-HR not only activates professional antigen-presenting cells (APCs), dendritic cells, but also effectively targets nasal epithelial cells, promotes antigen binding via sialic acid, and surprisingly provokes the antigen-presenting of nasal epithelial cells. We demonstrate that CCD is a promising intranasal vaccine adjuvant for provoking strong mucosal immunity and might be a candidate adjuvant for intranasal vaccine development for many types of infectious diseases, including COVID-19.https://doi.org/10.1038/s41467-023-38066-8 |
spellingShingle | Hong Lei Aqu Alu Jingyun Yang Xi He Cai He Wenyan Ren Zimin Chen Weiqi Hong Li Chen Xuemei He Li Yang Jiong Li Zhenling Wang Wei Wang Yuquan Wei Shuaiyao Lu Guangwen Lu Xiangrong Song Xiawei Wei Cationic crosslinked carbon dots-adjuvanted intranasal vaccine induces protective immunity against Omicron-included SARS-CoV-2 variants Nature Communications |
title | Cationic crosslinked carbon dots-adjuvanted intranasal vaccine induces protective immunity against Omicron-included SARS-CoV-2 variants |
title_full | Cationic crosslinked carbon dots-adjuvanted intranasal vaccine induces protective immunity against Omicron-included SARS-CoV-2 variants |
title_fullStr | Cationic crosslinked carbon dots-adjuvanted intranasal vaccine induces protective immunity against Omicron-included SARS-CoV-2 variants |
title_full_unstemmed | Cationic crosslinked carbon dots-adjuvanted intranasal vaccine induces protective immunity against Omicron-included SARS-CoV-2 variants |
title_short | Cationic crosslinked carbon dots-adjuvanted intranasal vaccine induces protective immunity against Omicron-included SARS-CoV-2 variants |
title_sort | cationic crosslinked carbon dots adjuvanted intranasal vaccine induces protective immunity against omicron included sars cov 2 variants |
url | https://doi.org/10.1038/s41467-023-38066-8 |
work_keys_str_mv | AT honglei cationiccrosslinkedcarbondotsadjuvantedintranasalvaccineinducesprotectiveimmunityagainstomicronincludedsarscov2variants AT aqualu cationiccrosslinkedcarbondotsadjuvantedintranasalvaccineinducesprotectiveimmunityagainstomicronincludedsarscov2variants AT jingyunyang cationiccrosslinkedcarbondotsadjuvantedintranasalvaccineinducesprotectiveimmunityagainstomicronincludedsarscov2variants AT xihe cationiccrosslinkedcarbondotsadjuvantedintranasalvaccineinducesprotectiveimmunityagainstomicronincludedsarscov2variants AT caihe cationiccrosslinkedcarbondotsadjuvantedintranasalvaccineinducesprotectiveimmunityagainstomicronincludedsarscov2variants AT wenyanren cationiccrosslinkedcarbondotsadjuvantedintranasalvaccineinducesprotectiveimmunityagainstomicronincludedsarscov2variants AT ziminchen cationiccrosslinkedcarbondotsadjuvantedintranasalvaccineinducesprotectiveimmunityagainstomicronincludedsarscov2variants AT weiqihong cationiccrosslinkedcarbondotsadjuvantedintranasalvaccineinducesprotectiveimmunityagainstomicronincludedsarscov2variants AT lichen cationiccrosslinkedcarbondotsadjuvantedintranasalvaccineinducesprotectiveimmunityagainstomicronincludedsarscov2variants AT xuemeihe cationiccrosslinkedcarbondotsadjuvantedintranasalvaccineinducesprotectiveimmunityagainstomicronincludedsarscov2variants AT liyang cationiccrosslinkedcarbondotsadjuvantedintranasalvaccineinducesprotectiveimmunityagainstomicronincludedsarscov2variants AT jiongli cationiccrosslinkedcarbondotsadjuvantedintranasalvaccineinducesprotectiveimmunityagainstomicronincludedsarscov2variants AT zhenlingwang cationiccrosslinkedcarbondotsadjuvantedintranasalvaccineinducesprotectiveimmunityagainstomicronincludedsarscov2variants AT weiwang cationiccrosslinkedcarbondotsadjuvantedintranasalvaccineinducesprotectiveimmunityagainstomicronincludedsarscov2variants AT yuquanwei cationiccrosslinkedcarbondotsadjuvantedintranasalvaccineinducesprotectiveimmunityagainstomicronincludedsarscov2variants AT shuaiyaolu cationiccrosslinkedcarbondotsadjuvantedintranasalvaccineinducesprotectiveimmunityagainstomicronincludedsarscov2variants AT guangwenlu cationiccrosslinkedcarbondotsadjuvantedintranasalvaccineinducesprotectiveimmunityagainstomicronincludedsarscov2variants AT xiangrongsong cationiccrosslinkedcarbondotsadjuvantedintranasalvaccineinducesprotectiveimmunityagainstomicronincludedsarscov2variants AT xiaweiwei cationiccrosslinkedcarbondotsadjuvantedintranasalvaccineinducesprotectiveimmunityagainstomicronincludedsarscov2variants |