RBD-displaying OMV nanovaccine boosts immunity against SARS-CoV-2
Abstract Background Since the emergence of SARS-CoV-2, the causative agent of COVID-19, the global health landscape has confronted an unprecedented and formidable challenge. The SARS-CoV-2 receptor-binding domain (RBD) is a key antigen in vaccine design. However, its low immunogenicity has been a hu...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-02-01
|
| Series: | Journal of Nanobiotechnology |
| Online Access: | https://doi.org/10.1186/s12951-025-03191-7 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1823861680410460160 |
|---|---|
| author | Rang Feng Ruo-Yi Xue Chang Liu Guo-Cheng Li Yan Deng Zhe Jin Jing-Yi Liu Shan-Shan Zhang Hao Cheng Man-Ying Guo Quan-Ming Zou Hai-Bo Li |
| author_facet | Rang Feng Ruo-Yi Xue Chang Liu Guo-Cheng Li Yan Deng Zhe Jin Jing-Yi Liu Shan-Shan Zhang Hao Cheng Man-Ying Guo Quan-Ming Zou Hai-Bo Li |
| author_sort | Rang Feng |
| collection | DOAJ |
| description | Abstract Background Since the emergence of SARS-CoV-2, the causative agent of COVID-19, the global health landscape has confronted an unprecedented and formidable challenge. The SARS-CoV-2 receptor-binding domain (RBD) is a key antigen in vaccine design. However, its low immunogenicity has been a hurdle, resulting in the production of minimal anti-RBD antibodies even when combined with alum adjuvant. Outer membrane vesicles (OMVs), secreted by Gram-negative bacteria, are nanospherical structures that can display or deliver antigens while also providing adjuvant activity through pathogen-associated molecular patterns (PAMPs). Results In this study, we utilized the SpyTag (ST)/SpyCatcher (SC) bioconjugation system to couple OMV and SARS-CoV-2 RBD in vitro. We successfully prepared a ‘plug-and-display’ nanovaccine OMV-RBD, which demonstrated good safety profiles and promoted the uptake of antigens by DCs and the maturation of BMDCs by activating TLR3 and NOD2 signaling pathways. Both intranasal and intramuscular immunization with OMV-RBD vaccine elicited robust antigen-specific humoral and cellular immune responses. Importantly, the induced antibodies effectively inhibited the binding of RBD to human angiotensin-converting enzyme 2 (hACE2) and neutralized SARS-CoV-2 pseudoviruses. Conclusions This vaccine platform offers an alternative strategy for developing recombinant subunit vaccines against SARS-CoV-2, potentially enhancing immune responses and improving vaccine efficacy. Graphical abstract |
| format | Article |
| id | doaj-art-d32ec5c3d46842578e3a0a3811aae6b3 |
| institution | Kabale University |
| issn | 1477-3155 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj-art-d32ec5c3d46842578e3a0a3811aae6b32025-02-09T12:52:59ZengBMCJournal of Nanobiotechnology1477-31552025-02-0123111910.1186/s12951-025-03191-7RBD-displaying OMV nanovaccine boosts immunity against SARS-CoV-2Rang Feng0Ruo-Yi Xue1Chang Liu2Guo-Cheng Li3Yan Deng4Zhe Jin5Jing-Yi Liu6Shan-Shan Zhang7Hao Cheng8Man-Ying Guo9Quan-Ming Zou10Hai-Bo Li11National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University (Army Medical University)National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University (Army Medical University)National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University (Army Medical University)National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University (Army Medical University)National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University (Army Medical University)National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University (Army Medical University)National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University (Army Medical University)National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University (Army Medical University)National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University (Army Medical University)Department of Laboratory Pathology, Chinese People’s Liberation Army No. 72 HospitalNational Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University (Army Medical University)National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University (Army Medical University)Abstract Background Since the emergence of SARS-CoV-2, the causative agent of COVID-19, the global health landscape has confronted an unprecedented and formidable challenge. The SARS-CoV-2 receptor-binding domain (RBD) is a key antigen in vaccine design. However, its low immunogenicity has been a hurdle, resulting in the production of minimal anti-RBD antibodies even when combined with alum adjuvant. Outer membrane vesicles (OMVs), secreted by Gram-negative bacteria, are nanospherical structures that can display or deliver antigens while also providing adjuvant activity through pathogen-associated molecular patterns (PAMPs). Results In this study, we utilized the SpyTag (ST)/SpyCatcher (SC) bioconjugation system to couple OMV and SARS-CoV-2 RBD in vitro. We successfully prepared a ‘plug-and-display’ nanovaccine OMV-RBD, which demonstrated good safety profiles and promoted the uptake of antigens by DCs and the maturation of BMDCs by activating TLR3 and NOD2 signaling pathways. Both intranasal and intramuscular immunization with OMV-RBD vaccine elicited robust antigen-specific humoral and cellular immune responses. Importantly, the induced antibodies effectively inhibited the binding of RBD to human angiotensin-converting enzyme 2 (hACE2) and neutralized SARS-CoV-2 pseudoviruses. Conclusions This vaccine platform offers an alternative strategy for developing recombinant subunit vaccines against SARS-CoV-2, potentially enhancing immune responses and improving vaccine efficacy. Graphical abstracthttps://doi.org/10.1186/s12951-025-03191-7 |
| spellingShingle | Rang Feng Ruo-Yi Xue Chang Liu Guo-Cheng Li Yan Deng Zhe Jin Jing-Yi Liu Shan-Shan Zhang Hao Cheng Man-Ying Guo Quan-Ming Zou Hai-Bo Li RBD-displaying OMV nanovaccine boosts immunity against SARS-CoV-2 Journal of Nanobiotechnology |
| title | RBD-displaying OMV nanovaccine boosts immunity against SARS-CoV-2 |
| title_full | RBD-displaying OMV nanovaccine boosts immunity against SARS-CoV-2 |
| title_fullStr | RBD-displaying OMV nanovaccine boosts immunity against SARS-CoV-2 |
| title_full_unstemmed | RBD-displaying OMV nanovaccine boosts immunity against SARS-CoV-2 |
| title_short | RBD-displaying OMV nanovaccine boosts immunity against SARS-CoV-2 |
| title_sort | rbd displaying omv nanovaccine boosts immunity against sars cov 2 |
| url | https://doi.org/10.1186/s12951-025-03191-7 |
| work_keys_str_mv | AT rangfeng rbddisplayingomvnanovaccineboostsimmunityagainstsarscov2 AT ruoyixue rbddisplayingomvnanovaccineboostsimmunityagainstsarscov2 AT changliu rbddisplayingomvnanovaccineboostsimmunityagainstsarscov2 AT guochengli rbddisplayingomvnanovaccineboostsimmunityagainstsarscov2 AT yandeng rbddisplayingomvnanovaccineboostsimmunityagainstsarscov2 AT zhejin rbddisplayingomvnanovaccineboostsimmunityagainstsarscov2 AT jingyiliu rbddisplayingomvnanovaccineboostsimmunityagainstsarscov2 AT shanshanzhang rbddisplayingomvnanovaccineboostsimmunityagainstsarscov2 AT haocheng rbddisplayingomvnanovaccineboostsimmunityagainstsarscov2 AT manyingguo rbddisplayingomvnanovaccineboostsimmunityagainstsarscov2 AT quanmingzou rbddisplayingomvnanovaccineboostsimmunityagainstsarscov2 AT haiboli rbddisplayingomvnanovaccineboostsimmunityagainstsarscov2 |