Delivery of dendritic cells targeting 3M2e-HA2 nanoparticles with a CpG adjuvant via lysosomal escape of Salmonella enhances protection against H9N2 avian influenza virus
Avian influenza virus (AIV) subtype H9N2 still poses a great threat to the poultry farming industry and public health worldwide, and the development of a new influenza vaccine that is safe and conservative and able to address influenza virus mutations is highly promising for application. HA2, the ne...
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Elsevier
2025-01-01
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| Series: | Poultry Science |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0032579124011945 |
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| author | Futing Jia Wenfeng Wang Yawen Tian Ainul Zahra Yingkai He Chongbo Ge Tongyu Zhang Mingyue Wang Jingshuo Gong Gerui Zhang Guilian Yang Wentao Yang Chunwei Shi Jianzhong Wang Haibin Huang Xin Cao Yang Zeng Nan Wang Zhannan Wang Chunfeng Wang Yanlong Jiang |
| author_facet | Futing Jia Wenfeng Wang Yawen Tian Ainul Zahra Yingkai He Chongbo Ge Tongyu Zhang Mingyue Wang Jingshuo Gong Gerui Zhang Guilian Yang Wentao Yang Chunwei Shi Jianzhong Wang Haibin Huang Xin Cao Yang Zeng Nan Wang Zhannan Wang Chunfeng Wang Yanlong Jiang |
| author_sort | Futing Jia |
| collection | DOAJ |
| description | Avian influenza virus (AIV) subtype H9N2 still poses a great threat to the poultry farming industry and public health worldwide, and the development of a new influenza vaccine that is safe and conservative and able to address influenza virus mutations is highly promising for application. HA2, the neck of the HA protein, and M2e, the extracellular N-terminal structural domain of the M2 protein, are conserved and effective protective antigens.In this study, the HA2 sequences were fused with three M2e copies (H9N2, H1N1 and H5N1) to the norovirus VP1 protein via the SpyTag-SpyCatcher platform to form self-assembled nanoparticles and display antigenic proteins on its surface, yielding pYL262. The chicken dendritic cells (DCs) targeting the nanobody phage-54 were then fused to HA2-3M2e to yield pYL327. Finally, a synthesized 20-repeat CpG adjuvant gene fragment was inserted into pYL327, resulting in the plasmid pYL331. All the constructed plasmids were then transformed into the sifA gene-deficient Salmonella vector χYL56 for oral immunization.The results showed that sifA-deficient Salmonella could efficiently increase antigen-specific mucosal sIgA antibody titers, especially in alveolar lavage samples, whereas the presence of the phage-54 nanobody could dramatically increase intracellular IFN-γ mRNA levels, indicating its ability to enhance the Th1-type immune response. Finally, the presence of the CpG adjuvant clearly increased T-cell proliferation and promoted DC activation, with elevated splenic TLR21 levels observed. Strikingly, after oral immunization with χYL56 (pYL331), chickens were protected against challenge with the G57 genotype H9N2 virus, which presented similar or even better levels of virus shedding and body weight gain compared with the commercial inactivated vaccine, providing a new option for controlling H9N2 virus infection in the future. |
| format | Article |
| id | doaj-art-9ff1ee416096473388a68d31d1f1d77a |
| institution | Kabale University |
| issn | 0032-5791 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Poultry Science |
| spelling | doaj-art-9ff1ee416096473388a68d31d1f1d77a2025-01-22T05:40:44ZengElsevierPoultry Science0032-57912025-01-011041104616Delivery of dendritic cells targeting 3M2e-HA2 nanoparticles with a CpG adjuvant via lysosomal escape of Salmonella enhances protection against H9N2 avian influenza virusFuting Jia0Wenfeng Wang1Yawen Tian2Ainul Zahra3Yingkai He4Chongbo Ge5Tongyu Zhang6Mingyue Wang7Jingshuo Gong8Gerui Zhang9Guilian Yang10Wentao Yang11Chunwei Shi12Jianzhong Wang13Haibin Huang14Xin Cao15Yang Zeng16Nan Wang17Zhannan Wang18Chunfeng Wang19Yanlong Jiang20These authors contribute equally to this work.; College of Animal Medicine, Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, Changchun, 130118, ChinaThese authors contribute equally to this work.; College of Animal Medicine, Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, Changchun, 130118, ChinaThese authors contribute equally to this work.; College of Animal Medicine, Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, Changchun, 130118, ChinaCollege of Animal Medicine, Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, Changchun, 130118, ChinaCollege of Animal Medicine, Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, Changchun, 130118, ChinaCollege of Animal Medicine, Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, Changchun, 130118, ChinaCollege of Animal Medicine, Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, Changchun, 130118, ChinaCollege of Animal Medicine, Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, Changchun, 130118, ChinaCollege of Animal Medicine, Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, Changchun, 130118, ChinaCollege of Animal Medicine, Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, Changchun, 130118, ChinaCollege of Animal Medicine, Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, Changchun, 130118, ChinaCollege of Animal Medicine, Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, Changchun, 130118, ChinaCollege of Animal Medicine, Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, Changchun, 130118, ChinaCollege of Animal Medicine, Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, Changchun, 130118, ChinaCollege of Animal Medicine, Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, Changchun, 130118, ChinaCollege of Animal Medicine, Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, Changchun, 130118, ChinaCollege of Animal Medicine, Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, Changchun, 130118, ChinaCollege of Animal Medicine, Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, Changchun, 130118, ChinaCorrespondence authors.; College of Animal Medicine, Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, Changchun, 130118, ChinaCorrespondence authors.; College of Animal Medicine, Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, Changchun, 130118, ChinaCorrespondence authors.; College of Animal Medicine, Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, Changchun, 130118, ChinaAvian influenza virus (AIV) subtype H9N2 still poses a great threat to the poultry farming industry and public health worldwide, and the development of a new influenza vaccine that is safe and conservative and able to address influenza virus mutations is highly promising for application. HA2, the neck of the HA protein, and M2e, the extracellular N-terminal structural domain of the M2 protein, are conserved and effective protective antigens.In this study, the HA2 sequences were fused with three M2e copies (H9N2, H1N1 and H5N1) to the norovirus VP1 protein via the SpyTag-SpyCatcher platform to form self-assembled nanoparticles and display antigenic proteins on its surface, yielding pYL262. The chicken dendritic cells (DCs) targeting the nanobody phage-54 were then fused to HA2-3M2e to yield pYL327. Finally, a synthesized 20-repeat CpG adjuvant gene fragment was inserted into pYL327, resulting in the plasmid pYL331. All the constructed plasmids were then transformed into the sifA gene-deficient Salmonella vector χYL56 for oral immunization.The results showed that sifA-deficient Salmonella could efficiently increase antigen-specific mucosal sIgA antibody titers, especially in alveolar lavage samples, whereas the presence of the phage-54 nanobody could dramatically increase intracellular IFN-γ mRNA levels, indicating its ability to enhance the Th1-type immune response. Finally, the presence of the CpG adjuvant clearly increased T-cell proliferation and promoted DC activation, with elevated splenic TLR21 levels observed. Strikingly, after oral immunization with χYL56 (pYL331), chickens were protected against challenge with the G57 genotype H9N2 virus, which presented similar or even better levels of virus shedding and body weight gain compared with the commercial inactivated vaccine, providing a new option for controlling H9N2 virus infection in the future.http://www.sciencedirect.com/science/article/pii/S0032579124011945H9N2 influenza virusSifA-mutant SalmonellaNanoparticle vaccineDendritic cell targetingCpG adjuvant |
| spellingShingle | Futing Jia Wenfeng Wang Yawen Tian Ainul Zahra Yingkai He Chongbo Ge Tongyu Zhang Mingyue Wang Jingshuo Gong Gerui Zhang Guilian Yang Wentao Yang Chunwei Shi Jianzhong Wang Haibin Huang Xin Cao Yang Zeng Nan Wang Zhannan Wang Chunfeng Wang Yanlong Jiang Delivery of dendritic cells targeting 3M2e-HA2 nanoparticles with a CpG adjuvant via lysosomal escape of Salmonella enhances protection against H9N2 avian influenza virus Poultry Science H9N2 influenza virus SifA-mutant Salmonella Nanoparticle vaccine Dendritic cell targeting CpG adjuvant |
| title | Delivery of dendritic cells targeting 3M2e-HA2 nanoparticles with a CpG adjuvant via lysosomal escape of Salmonella enhances protection against H9N2 avian influenza virus |
| title_full | Delivery of dendritic cells targeting 3M2e-HA2 nanoparticles with a CpG adjuvant via lysosomal escape of Salmonella enhances protection against H9N2 avian influenza virus |
| title_fullStr | Delivery of dendritic cells targeting 3M2e-HA2 nanoparticles with a CpG adjuvant via lysosomal escape of Salmonella enhances protection against H9N2 avian influenza virus |
| title_full_unstemmed | Delivery of dendritic cells targeting 3M2e-HA2 nanoparticles with a CpG adjuvant via lysosomal escape of Salmonella enhances protection against H9N2 avian influenza virus |
| title_short | Delivery of dendritic cells targeting 3M2e-HA2 nanoparticles with a CpG adjuvant via lysosomal escape of Salmonella enhances protection against H9N2 avian influenza virus |
| title_sort | delivery of dendritic cells targeting 3m2e ha2 nanoparticles with a cpg adjuvant via lysosomal escape of salmonella enhances protection against h9n2 avian influenza virus |
| topic | H9N2 influenza virus SifA-mutant Salmonella Nanoparticle vaccine Dendritic cell targeting CpG adjuvant |
| url | http://www.sciencedirect.com/science/article/pii/S0032579124011945 |
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