Salmonella-Delivered COBRA-HA1 Antigen Derived from H1N1 Hemagglutinin Sequences Elicits Broad-Spectrum Protection Against Influenza A Subtypes
A universal vaccine is in high demand to address the uncertainties of antigenic drift and the reduced effectiveness of current influenza vaccines. In this study, a strategy called computationally optimized broadly reactive antigen (COBRA) was used to generate a consensus sequence of the hemagglutini...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-01-01
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| Series: | Engineering |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2095809923002989 |
| _version_ | 1797200916234895360 |
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| author | Ram Prasad Aganja Amal Senevirathne Chandran Sivasankar John Hwa Lee |
| author_facet | Ram Prasad Aganja Amal Senevirathne Chandran Sivasankar John Hwa Lee |
| author_sort | Ram Prasad Aganja |
| collection | DOAJ |
| description | A universal vaccine is in high demand to address the uncertainties of antigenic drift and the reduced effectiveness of current influenza vaccines. In this study, a strategy called computationally optimized broadly reactive antigen (COBRA) was used to generate a consensus sequence of the hemagglutinin globular head portion (HA1) of influenza virus samples collected from 1918 to 2021 to trace evolutionary changes and incorporate them into the designed constructs. Constructs carrying different HA1 regions were delivered into eukaryotic cells by Salmonella-mediated bactofection using a Semliki Forest virus RNA-dependent RNA polymerase (RdRp)-based eukaryotic expression system, pJHL204. Recombinant protein expression was confirmed by Western blot and immunofluorescence assays. Mice immunized with the designed constructs produced a humoral response, with a significant increase in immunoglobulin G (IgG) levels, and a cell-mediated immune response, including a 1.5-fold increase in CD4+ and CD8+ T cells. Specifically, constructs #1 and #5 increased the production of interferon-γ (IFN-γ) producing CD4+ and CD8+ T cells, skewing the response toward the T helper type 1 cell (Th1) pathway. Additionally, interleukin-4 (IL-4)-producing T cells were upregulated 4-fold. Protective efficacy was demonstrated, with up to 4-fold higher production of neutralizing antibodies and a hemagglutination inhibition titer > 40 against the selected viral strains. The designed constructs conferred a broadly protective immune response, resulting in a notable reduction in viral titer and minimal inflammation in the lungs of mice challenged with the influenza A/PR8/34, A/Brisbane/59/2007, A/California/07/2009, KBPV VR-92, and NCCP 43021 strains. This discovery revolutionizes influenza vaccine design and delivery; Salmonella-mediated COBRA-HA1 is a highly effective in vivo antigen presentation strategy. This approach can effectively combat seasonal H1N1 influenza strains and potential pandemic outbreaks. |
| first_indexed | 2024-04-24T07:39:15Z |
| format | Article |
| id | doaj.art-dbc7803b0e3a4568b418c56fc5487bb2 |
| institution | Directory Open Access Journal |
| issn | 2095-8099 |
| language | English |
| last_indexed | 2024-04-24T07:39:15Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Engineering |
| spelling | doaj.art-dbc7803b0e3a4568b418c56fc5487bb22024-04-20T04:17:21ZengElsevierEngineering2095-80992024-01-01324156Salmonella-Delivered COBRA-HA1 Antigen Derived from H1N1 Hemagglutinin Sequences Elicits Broad-Spectrum Protection Against Influenza A SubtypesRam Prasad Aganja0Amal Senevirathne1Chandran Sivasankar2John Hwa Lee3Department of Veterinary Public Health, College of Veterinary Medicine, Jeonbuk National University, Iksan 54596, Republic of KoreaDepartment of Preventive Medicine, College of Veterinary Medicine, Chungnam National University, Daejeon 34134, Republic of KoreaDepartment of Veterinary Public Health, College of Veterinary Medicine, Jeonbuk National University, Iksan 54596, Republic of KoreaDepartment of Veterinary Public Health, College of Veterinary Medicine, Jeonbuk National University, Iksan 54596, Republic of Korea; Corresponding author.A universal vaccine is in high demand to address the uncertainties of antigenic drift and the reduced effectiveness of current influenza vaccines. In this study, a strategy called computationally optimized broadly reactive antigen (COBRA) was used to generate a consensus sequence of the hemagglutinin globular head portion (HA1) of influenza virus samples collected from 1918 to 2021 to trace evolutionary changes and incorporate them into the designed constructs. Constructs carrying different HA1 regions were delivered into eukaryotic cells by Salmonella-mediated bactofection using a Semliki Forest virus RNA-dependent RNA polymerase (RdRp)-based eukaryotic expression system, pJHL204. Recombinant protein expression was confirmed by Western blot and immunofluorescence assays. Mice immunized with the designed constructs produced a humoral response, with a significant increase in immunoglobulin G (IgG) levels, and a cell-mediated immune response, including a 1.5-fold increase in CD4+ and CD8+ T cells. Specifically, constructs #1 and #5 increased the production of interferon-γ (IFN-γ) producing CD4+ and CD8+ T cells, skewing the response toward the T helper type 1 cell (Th1) pathway. Additionally, interleukin-4 (IL-4)-producing T cells were upregulated 4-fold. Protective efficacy was demonstrated, with up to 4-fold higher production of neutralizing antibodies and a hemagglutination inhibition titer > 40 against the selected viral strains. The designed constructs conferred a broadly protective immune response, resulting in a notable reduction in viral titer and minimal inflammation in the lungs of mice challenged with the influenza A/PR8/34, A/Brisbane/59/2007, A/California/07/2009, KBPV VR-92, and NCCP 43021 strains. This discovery revolutionizes influenza vaccine design and delivery; Salmonella-mediated COBRA-HA1 is a highly effective in vivo antigen presentation strategy. This approach can effectively combat seasonal H1N1 influenza strains and potential pandemic outbreaks.http://www.sciencedirect.com/science/article/pii/S2095809923002989COBRAInfluenza ASalmonellaVaccineBroad spectral protection |
| spellingShingle | Ram Prasad Aganja Amal Senevirathne Chandran Sivasankar John Hwa Lee Salmonella-Delivered COBRA-HA1 Antigen Derived from H1N1 Hemagglutinin Sequences Elicits Broad-Spectrum Protection Against Influenza A Subtypes Engineering COBRA Influenza A Salmonella Vaccine Broad spectral protection |
| title | Salmonella-Delivered COBRA-HA1 Antigen Derived from H1N1 Hemagglutinin Sequences Elicits Broad-Spectrum Protection Against Influenza A Subtypes |
| title_full | Salmonella-Delivered COBRA-HA1 Antigen Derived from H1N1 Hemagglutinin Sequences Elicits Broad-Spectrum Protection Against Influenza A Subtypes |
| title_fullStr | Salmonella-Delivered COBRA-HA1 Antigen Derived from H1N1 Hemagglutinin Sequences Elicits Broad-Spectrum Protection Against Influenza A Subtypes |
| title_full_unstemmed | Salmonella-Delivered COBRA-HA1 Antigen Derived from H1N1 Hemagglutinin Sequences Elicits Broad-Spectrum Protection Against Influenza A Subtypes |
| title_short | Salmonella-Delivered COBRA-HA1 Antigen Derived from H1N1 Hemagglutinin Sequences Elicits Broad-Spectrum Protection Against Influenza A Subtypes |
| title_sort | salmonella delivered cobra ha1 antigen derived from h1n1 hemagglutinin sequences elicits broad spectrum protection against influenza a subtypes |
| topic | COBRA Influenza A Salmonella Vaccine Broad spectral protection |
| url | http://www.sciencedirect.com/science/article/pii/S2095809923002989 |
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