Enhanced mucosal immune responses and reduced viral load in the respiratory tract of ferrets to intranasal lipid nanoparticle-based SARS-CoV-2 proteins and mRNA vaccines
Abstract Background Unlike the injectable vaccines, intranasal lipid nanoparticle (NP)-based adjuvanted vaccine is promising to protect against local infection and viral transmission. Infection of ferrets with SARS-CoV-2 results in typical respiratory disease and pathology akin to in humans, suggest...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-02-01
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| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12951-023-01816-3 |
| _version_ | 1827982882417672192 |
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| author | Patricia A. Boley Carolyn M. Lee Jennifer Schrock Kush Kumar Yadav Veerupaxagouda Patil Raksha Suresh Songqing Lu Maoqi Mark Feng Juliette Hanson Rudra Channappanavar Scott P. Kenney Gourapura J. Renukaradhya |
| author_facet | Patricia A. Boley Carolyn M. Lee Jennifer Schrock Kush Kumar Yadav Veerupaxagouda Patil Raksha Suresh Songqing Lu Maoqi Mark Feng Juliette Hanson Rudra Channappanavar Scott P. Kenney Gourapura J. Renukaradhya |
| author_sort | Patricia A. Boley |
| collection | DOAJ |
| description | Abstract Background Unlike the injectable vaccines, intranasal lipid nanoparticle (NP)-based adjuvanted vaccine is promising to protect against local infection and viral transmission. Infection of ferrets with SARS-CoV-2 results in typical respiratory disease and pathology akin to in humans, suggesting that the ferret model may be ideal for intranasal vaccine studies. Results We developed SARS-CoV-2 subunit vaccine containing both Spike receptor binding domain (S-RBD) and Nucleocapsid (N) proteins (NP-COVID-Proteins) or their mRNA (NP-COVID-mRNA) and NP-monosodium urate adjuvant. Both the candidate vaccines in intranasal vaccinated aged ferrets substantially reduced the replicating virus in the entire respiratory tract. Specifically, the NP-COVID-Proteins vaccine did relatively better in clearing the virus from the nasal passage early post challenge infection. The immune gene expression in NP-COVID-Proteins vaccinates indicated increased levels of mRNA of IFNα, MCP1 and IL-4 in lungs and nasal turbinates, and IFNγ and IL-2 in lungs; while proinflammatory mediators IL-1β and IL-8 mRNA levels in lungs were downregulated. In NP-COVID-Proteins vaccinated ferrets S-RBD and N protein specific IgG antibodies in the serum were substantially increased at both day post challenge (DPC) 7 and DPC 14, while the virus neutralizing antibody titers were relatively better induced by mRNA versus the proteins-based vaccine. In conclusion, intranasal NP-COVID-Proteins vaccine induced balanced Th1 and Th2 immune responses in the respiratory tract, while NP-COVID-mRNA vaccine primarily elicited antibody responses. Conclusions Intranasal NP-COVID-Proteins vaccine may be an ideal candidate to elicit increased breadth of immunity against SARS-CoV-2 variants. |
| first_indexed | 2024-04-09T22:38:58Z |
| format | Article |
| id | doaj.art-1511380eced54d55a8e15b05d169202d |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-04-09T22:38:58Z |
| publishDate | 2023-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-1511380eced54d55a8e15b05d169202d2023-03-22T12:16:46ZengBMCJournal of Nanobiotechnology1477-31552023-02-0121111610.1186/s12951-023-01816-3Enhanced mucosal immune responses and reduced viral load in the respiratory tract of ferrets to intranasal lipid nanoparticle-based SARS-CoV-2 proteins and mRNA vaccinesPatricia A. Boley0Carolyn M. Lee1Jennifer Schrock2Kush Kumar Yadav3Veerupaxagouda Patil4Raksha Suresh5Songqing Lu6Maoqi Mark Feng7Juliette Hanson8Rudra Channappanavar9Scott P. Kenney10Gourapura J. Renukaradhya11Center for Food Animal Health, Department of Animal Sciences, The Ohio State UniversityCenter for Food Animal Health, Department of Animal Sciences, The Ohio State UniversityCenter for Food Animal Health, Department of Animal Sciences, The Ohio State UniversityCenter for Food Animal Health, Department of Animal Sciences, The Ohio State UniversityCenter for Food Animal Health, Department of Animal Sciences, The Ohio State UniversityCenter for Food Animal Health, Department of Animal Sciences, The Ohio State UniversityDynamic Entropy Technology LLCDynamic Entropy Technology LLCCenter for Food Animal Health, Department of Animal Sciences, The Ohio State UniversityDepartment of Veterinary Pathobiology, Oklahoma Center for Respiratory and Infectious Diseases, Oklahoma State UniversityCenter for Food Animal Health, Department of Animal Sciences, The Ohio State UniversityCenter for Food Animal Health, Department of Animal Sciences, The Ohio State UniversityAbstract Background Unlike the injectable vaccines, intranasal lipid nanoparticle (NP)-based adjuvanted vaccine is promising to protect against local infection and viral transmission. Infection of ferrets with SARS-CoV-2 results in typical respiratory disease and pathology akin to in humans, suggesting that the ferret model may be ideal for intranasal vaccine studies. Results We developed SARS-CoV-2 subunit vaccine containing both Spike receptor binding domain (S-RBD) and Nucleocapsid (N) proteins (NP-COVID-Proteins) or their mRNA (NP-COVID-mRNA) and NP-monosodium urate adjuvant. Both the candidate vaccines in intranasal vaccinated aged ferrets substantially reduced the replicating virus in the entire respiratory tract. Specifically, the NP-COVID-Proteins vaccine did relatively better in clearing the virus from the nasal passage early post challenge infection. The immune gene expression in NP-COVID-Proteins vaccinates indicated increased levels of mRNA of IFNα, MCP1 and IL-4 in lungs and nasal turbinates, and IFNγ and IL-2 in lungs; while proinflammatory mediators IL-1β and IL-8 mRNA levels in lungs were downregulated. In NP-COVID-Proteins vaccinated ferrets S-RBD and N protein specific IgG antibodies in the serum were substantially increased at both day post challenge (DPC) 7 and DPC 14, while the virus neutralizing antibody titers were relatively better induced by mRNA versus the proteins-based vaccine. In conclusion, intranasal NP-COVID-Proteins vaccine induced balanced Th1 and Th2 immune responses in the respiratory tract, while NP-COVID-mRNA vaccine primarily elicited antibody responses. Conclusions Intranasal NP-COVID-Proteins vaccine may be an ideal candidate to elicit increased breadth of immunity against SARS-CoV-2 variants.https://doi.org/10.1186/s12951-023-01816-3Lipid nanoparticlesIntranasal vaccinationSubunit antigensmRNAFerrets |
| spellingShingle | Patricia A. Boley Carolyn M. Lee Jennifer Schrock Kush Kumar Yadav Veerupaxagouda Patil Raksha Suresh Songqing Lu Maoqi Mark Feng Juliette Hanson Rudra Channappanavar Scott P. Kenney Gourapura J. Renukaradhya Enhanced mucosal immune responses and reduced viral load in the respiratory tract of ferrets to intranasal lipid nanoparticle-based SARS-CoV-2 proteins and mRNA vaccines Journal of Nanobiotechnology Lipid nanoparticles Intranasal vaccination Subunit antigens mRNA Ferrets |
| title | Enhanced mucosal immune responses and reduced viral load in the respiratory tract of ferrets to intranasal lipid nanoparticle-based SARS-CoV-2 proteins and mRNA vaccines |
| title_full | Enhanced mucosal immune responses and reduced viral load in the respiratory tract of ferrets to intranasal lipid nanoparticle-based SARS-CoV-2 proteins and mRNA vaccines |
| title_fullStr | Enhanced mucosal immune responses and reduced viral load in the respiratory tract of ferrets to intranasal lipid nanoparticle-based SARS-CoV-2 proteins and mRNA vaccines |
| title_full_unstemmed | Enhanced mucosal immune responses and reduced viral load in the respiratory tract of ferrets to intranasal lipid nanoparticle-based SARS-CoV-2 proteins and mRNA vaccines |
| title_short | Enhanced mucosal immune responses and reduced viral load in the respiratory tract of ferrets to intranasal lipid nanoparticle-based SARS-CoV-2 proteins and mRNA vaccines |
| title_sort | enhanced mucosal immune responses and reduced viral load in the respiratory tract of ferrets to intranasal lipid nanoparticle based sars cov 2 proteins and mrna vaccines |
| topic | Lipid nanoparticles Intranasal vaccination Subunit antigens mRNA Ferrets |
| url | https://doi.org/10.1186/s12951-023-01816-3 |
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