Intranasally administered whole virion inactivated vaccine against clade 2.3.4.4b H5N1 influenza virus with optimized antigen and increased cross-protection
Abstract The global spread, frequent antigenic changes, and pandemic potential of clade 2.3.4.4b highly pathogenic avian influenza H5N1 underscore the urgent need for robust cross-protective vaccines. Here, we developed a clade 2.3.4.4b H5N1 whole inactivated virus (WIV) vaccine strain with improved...
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BMC
2025-05-01
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| Series: | Virology Journal |
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| Online Access: | https://doi.org/10.1186/s12985-025-02760-4 |
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| author | Jin-Ha Song Seung-Eun Son Ho-Won Kim Seung-Ji Kim Se-Hee An Chung-Young Lee Hyuk-Joon Kwon Kang-Seuk Choi |
| author_facet | Jin-Ha Song Seung-Eun Son Ho-Won Kim Seung-Ji Kim Se-Hee An Chung-Young Lee Hyuk-Joon Kwon Kang-Seuk Choi |
| author_sort | Jin-Ha Song |
| collection | DOAJ |
| description | Abstract The global spread, frequent antigenic changes, and pandemic potential of clade 2.3.4.4b highly pathogenic avian influenza H5N1 underscore the urgent need for robust cross-protective vaccines. Here, we developed a clade 2.3.4.4b H5N1 whole inactivated virus (WIV) vaccine strain with improved structural stability, productivity, and safety. By analyzing the evolutionary trends of clade 2.3.4.4b H5N1 viruses, we identified a key mutation (R90K) that increases heat stability while preserving antigenicity. Additionally, the PB2 gene of PR8 was replaced with a prototypical avian PB2 gene to increase replication efficiency in embryonated chicken eggs and reduce replication efficiency in mammalian cells, thereby improving productivity and biosafety. We found that our optimized clade 2.3.4.4b H5N1 vaccine strain (22W_KY), inactivated with binary ethylenimine (BEI), had superior antigen internalization into respiratory epithelial cells compared to those inactivated with formaldehyde or beta-propiolactone. Following intranasal administration to mice, the BEI-inactivated 22W_KY also elicited significantly stronger systemic IgG, mucosal IgA, and T-cell responses, especially in the lungs. Protective efficacy studies revealed that the BEI-inactivated 22W_KY vaccine provided complete protection against heterologous viral challenges and significant protection against heterosubtypic viral challenges, with no weight loss and complete suppression of the viral load in the respiratory tract in 2 of 3 mice. These results indicate that the BEI-inactivated 22W_KY vaccine could serve as a promising candidate for a safe, stable, cost-efficient, and broadly protective intranasal influenza vaccine against zoonotic and pandemic threats. |
| format | Article |
| id | doaj-art-2dd70f9791e8406f978e0ee89b5d1dc0 |
| institution | OA Journals |
| issn | 1743-422X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Virology Journal |
| spelling | doaj-art-2dd70f9791e8406f978e0ee89b5d1dc02025-08-20T01:51:59ZengBMCVirology Journal1743-422X2025-05-0122112510.1186/s12985-025-02760-4Intranasally administered whole virion inactivated vaccine against clade 2.3.4.4b H5N1 influenza virus with optimized antigen and increased cross-protectionJin-Ha Song0Seung-Eun Son1Ho-Won Kim2Seung-Ji Kim3Se-Hee An4Chung-Young Lee5Hyuk-Joon Kwon6Kang-Seuk Choi7Laboratory of Avian Diseases, College of Veterinary Medicine, Seoul National UniversityLaboratory of Avian Diseases, College of Veterinary Medicine, Seoul National UniversityLaboratory of Avian Diseases, College of Veterinary Medicine, Seoul National UniversityLaboratory of Avian Diseases, College of Veterinary Medicine, Seoul National UniversityAvian Influenza Research & Diagnostic Division, Animal and Plant Quarantine AgencyDepartment of Microbiology, College of Medicine, Kyungpook National UniversityLaboratory of Poultry Medicine, Department of Farm Animal Medicine, College of Veterinary Medicine, BK21 PLUS for Veterinary Science, Seoul National UniversityLaboratory of Avian Diseases, College of Veterinary Medicine, Seoul National UniversityAbstract The global spread, frequent antigenic changes, and pandemic potential of clade 2.3.4.4b highly pathogenic avian influenza H5N1 underscore the urgent need for robust cross-protective vaccines. Here, we developed a clade 2.3.4.4b H5N1 whole inactivated virus (WIV) vaccine strain with improved structural stability, productivity, and safety. By analyzing the evolutionary trends of clade 2.3.4.4b H5N1 viruses, we identified a key mutation (R90K) that increases heat stability while preserving antigenicity. Additionally, the PB2 gene of PR8 was replaced with a prototypical avian PB2 gene to increase replication efficiency in embryonated chicken eggs and reduce replication efficiency in mammalian cells, thereby improving productivity and biosafety. We found that our optimized clade 2.3.4.4b H5N1 vaccine strain (22W_KY), inactivated with binary ethylenimine (BEI), had superior antigen internalization into respiratory epithelial cells compared to those inactivated with formaldehyde or beta-propiolactone. Following intranasal administration to mice, the BEI-inactivated 22W_KY also elicited significantly stronger systemic IgG, mucosal IgA, and T-cell responses, especially in the lungs. Protective efficacy studies revealed that the BEI-inactivated 22W_KY vaccine provided complete protection against heterologous viral challenges and significant protection against heterosubtypic viral challenges, with no weight loss and complete suppression of the viral load in the respiratory tract in 2 of 3 mice. These results indicate that the BEI-inactivated 22W_KY vaccine could serve as a promising candidate for a safe, stable, cost-efficient, and broadly protective intranasal influenza vaccine against zoonotic and pandemic threats.https://doi.org/10.1186/s12985-025-02760-4Highly pathogenic avian influenza virusHeat stabilityWhole inactivated virus vaccineBinary ethylenimineIntranasal administrationCross-protection |
| spellingShingle | Jin-Ha Song Seung-Eun Son Ho-Won Kim Seung-Ji Kim Se-Hee An Chung-Young Lee Hyuk-Joon Kwon Kang-Seuk Choi Intranasally administered whole virion inactivated vaccine against clade 2.3.4.4b H5N1 influenza virus with optimized antigen and increased cross-protection Virology Journal Highly pathogenic avian influenza virus Heat stability Whole inactivated virus vaccine Binary ethylenimine Intranasal administration Cross-protection |
| title | Intranasally administered whole virion inactivated vaccine against clade 2.3.4.4b H5N1 influenza virus with optimized antigen and increased cross-protection |
| title_full | Intranasally administered whole virion inactivated vaccine against clade 2.3.4.4b H5N1 influenza virus with optimized antigen and increased cross-protection |
| title_fullStr | Intranasally administered whole virion inactivated vaccine against clade 2.3.4.4b H5N1 influenza virus with optimized antigen and increased cross-protection |
| title_full_unstemmed | Intranasally administered whole virion inactivated vaccine against clade 2.3.4.4b H5N1 influenza virus with optimized antigen and increased cross-protection |
| title_short | Intranasally administered whole virion inactivated vaccine against clade 2.3.4.4b H5N1 influenza virus with optimized antigen and increased cross-protection |
| title_sort | intranasally administered whole virion inactivated vaccine against clade 2 3 4 4b h5n1 influenza virus with optimized antigen and increased cross protection |
| topic | Highly pathogenic avian influenza virus Heat stability Whole inactivated virus vaccine Binary ethylenimine Intranasal administration Cross-protection |
| url | https://doi.org/10.1186/s12985-025-02760-4 |
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