A Model H5N2 Vaccine Strain for Dual Protection Against H5N1 and H9N2 Avian Influenza Viruses
<b>Background/Objective:</b> Highly pathogenic (HP) H5Nx and low-pathogenicity (LP) H9N2 avian influenza viruses (AIVs) pose global threats to the poultry industry and public health, highlighting the critical need for a dual-protective vaccine. <b>Methods:</b> In this study,...
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MDPI AG
2024-12-01
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| Online Access: | https://www.mdpi.com/2076-393X/13/1/22 |
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| author | Jin-Ha Song Seung-Eun Son Ho-Won Kim Se-Hee An Chung-Young Lee Hyuk-Joon Kwon Kang-Seuk Choi |
| author_facet | Jin-Ha Song Seung-Eun Son Ho-Won Kim Se-Hee An Chung-Young Lee Hyuk-Joon Kwon Kang-Seuk Choi |
| author_sort | Jin-Ha Song |
| collection | DOAJ |
| description | <b>Background/Objective:</b> Highly pathogenic (HP) H5Nx and low-pathogenicity (LP) H9N2 avian influenza viruses (AIVs) pose global threats to the poultry industry and public health, highlighting the critical need for a dual-protective vaccine. <b>Methods:</b> In this study, we generated a model PR8-derived recombinant H5N2 vaccine strain with hemagglutinin (HA) and neuraminidase (NA) genes from clade 2.3.2.1c H5N1 and Y439-like H9N2 viruses, respectively. To enhance the immunogenicity of the recombinant H5N2 vaccine strain, N-glycans of the HA2 subunit, NA, and M2e were modified. Additionally, we replaced M2e with avian M2e to enhance the antigenic homogeneity of AIVs for better protection. We also replaced PR8 PB2 with 01310 PB2, which is the PB2 gene derived from an LP H9N2 avian influenza virus, to eliminate pathogenicity in mammals. The productivity of the model vaccine strain (rvH5N2-aM2e-vPB2) in embryonated chicken eggs (ECEs), its potential risk of mammalian infection, and the immunogenicity associated with different inactivation methods (formaldehyde (F/A) vs. binary ethyleneimine (BEI)) were evaluated. <b>Results:</b> The rvH5N2-aM2e-vPB2 strain demonstrated high productivity in ECEs and exhibited complete inhibition of replication in mammalian cells. Furthermore, compared with using F/A inactivation, inactivation using BEI significantly enhanced the immune response, particularly against NA. This enhancement resulted in increased virus neutralization titers, supporting its efficacy for dual protection against H5Nx and H9N2 avian influenza viruses. Furthermore, we demonstrated that M2e-specific immune responses, difficult to induce with inactivated vaccines, can be effectively elicited with live vaccines, suggesting a strategy to enhance M2e immunogenicity in whole influenza virus vaccines. <b>Conclusions:</b> Finally, the successful development of the model rH5N2 vaccine strain is described; this strain provides dual protection, has potential applicability in regions where avian influenza is endemic, and can be used to promote the development of versatile H5N2 recombinant vaccines for effective avian influenza control. |
| format | Article |
| id | doaj-art-bc38998eeff94924832e8751c0ab2fa2 |
| institution | Kabale University |
| issn | 2076-393X |
| language | English |
| publishDate | 2024-12-01 |
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| series | Vaccines |
| spelling | doaj-art-bc38998eeff94924832e8751c0ab2fa22025-01-24T13:51:41ZengMDPI AGVaccines2076-393X2024-12-011312210.3390/vaccines13010022A Model H5N2 Vaccine Strain for Dual Protection Against H5N1 and H9N2 Avian Influenza VirusesJin-Ha Song0Seung-Eun Son1Ho-Won Kim2Se-Hee An3Chung-Young Lee4Hyuk-Joon Kwon5Kang-Seuk Choi6Laboratory of Avian Diseases, College of Veterinary Medicine, Seoul National University, Seoul 08826, Republic of KoreaLaboratory of Avian Diseases, College of Veterinary Medicine, Seoul National University, Seoul 08826, Republic of KoreaLaboratory of Avian Diseases, College of Veterinary Medicine, Seoul National University, Seoul 08826, Republic of KoreaAvian Influenza Research & Diagnostic Division, Animal and Plant Quarantine Agency, Gimcheon-si 39660, Republic of KoreaDepartment of Microbiology, College of Medicine, Kyungpook National University, Daegu 41944, Republic of KoreaResearch Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul 08826, Republic of KoreaLaboratory of Avian Diseases, College of Veterinary Medicine, Seoul National University, Seoul 08826, Republic of Korea<b>Background/Objective:</b> Highly pathogenic (HP) H5Nx and low-pathogenicity (LP) H9N2 avian influenza viruses (AIVs) pose global threats to the poultry industry and public health, highlighting the critical need for a dual-protective vaccine. <b>Methods:</b> In this study, we generated a model PR8-derived recombinant H5N2 vaccine strain with hemagglutinin (HA) and neuraminidase (NA) genes from clade 2.3.2.1c H5N1 and Y439-like H9N2 viruses, respectively. To enhance the immunogenicity of the recombinant H5N2 vaccine strain, N-glycans of the HA2 subunit, NA, and M2e were modified. Additionally, we replaced M2e with avian M2e to enhance the antigenic homogeneity of AIVs for better protection. We also replaced PR8 PB2 with 01310 PB2, which is the PB2 gene derived from an LP H9N2 avian influenza virus, to eliminate pathogenicity in mammals. The productivity of the model vaccine strain (rvH5N2-aM2e-vPB2) in embryonated chicken eggs (ECEs), its potential risk of mammalian infection, and the immunogenicity associated with different inactivation methods (formaldehyde (F/A) vs. binary ethyleneimine (BEI)) were evaluated. <b>Results:</b> The rvH5N2-aM2e-vPB2 strain demonstrated high productivity in ECEs and exhibited complete inhibition of replication in mammalian cells. Furthermore, compared with using F/A inactivation, inactivation using BEI significantly enhanced the immune response, particularly against NA. This enhancement resulted in increased virus neutralization titers, supporting its efficacy for dual protection against H5Nx and H9N2 avian influenza viruses. Furthermore, we demonstrated that M2e-specific immune responses, difficult to induce with inactivated vaccines, can be effectively elicited with live vaccines, suggesting a strategy to enhance M2e immunogenicity in whole influenza virus vaccines. <b>Conclusions:</b> Finally, the successful development of the model rH5N2 vaccine strain is described; this strain provides dual protection, has potential applicability in regions where avian influenza is endemic, and can be used to promote the development of versatile H5N2 recombinant vaccines for effective avian influenza control.https://www.mdpi.com/2076-393X/13/1/22dual protectionhighly pathogenic avian influenza virusH9N2 avian influenza virusbinary ethylenimine inactivationN-glycosylationNA immunity |
| spellingShingle | Jin-Ha Song Seung-Eun Son Ho-Won Kim Se-Hee An Chung-Young Lee Hyuk-Joon Kwon Kang-Seuk Choi A Model H5N2 Vaccine Strain for Dual Protection Against H5N1 and H9N2 Avian Influenza Viruses Vaccines dual protection highly pathogenic avian influenza virus H9N2 avian influenza virus binary ethylenimine inactivation N-glycosylation NA immunity |
| title | A Model H5N2 Vaccine Strain for Dual Protection Against H5N1 and H9N2 Avian Influenza Viruses |
| title_full | A Model H5N2 Vaccine Strain for Dual Protection Against H5N1 and H9N2 Avian Influenza Viruses |
| title_fullStr | A Model H5N2 Vaccine Strain for Dual Protection Against H5N1 and H9N2 Avian Influenza Viruses |
| title_full_unstemmed | A Model H5N2 Vaccine Strain for Dual Protection Against H5N1 and H9N2 Avian Influenza Viruses |
| title_short | A Model H5N2 Vaccine Strain for Dual Protection Against H5N1 and H9N2 Avian Influenza Viruses |
| title_sort | model h5n2 vaccine strain for dual protection against h5n1 and h9n2 avian influenza viruses |
| topic | dual protection highly pathogenic avian influenza virus H9N2 avian influenza virus binary ethylenimine inactivation N-glycosylation NA immunity |
| url | https://www.mdpi.com/2076-393X/13/1/22 |
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