Influenza Vaccine With Consensus Internal Antigens as Immunogens Provides Cross-Group Protection Against Influenza A Viruses
Given that continuing antigenic shift and drift of influenza A viruses result in the escape from previous vaccine-induced immune protection, a universal influenza vaccine has been actively sought. However, there were very few vaccines capable of eliciting cross-group ant-influenza immunity. Here, we...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-07-01
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| Series: | Frontiers in Microbiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fmicb.2019.01630/full |
| _version_ | 1811288253985193984 |
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| author | Xinci Xie Chen Zhao Qian He Tianyi Qiu Songhua Yuan Longfei Ding Lu Liu Lang Jiang Jing Wang Linxia Zhang Chao Zhang Xiang Wang Dongming Zhou Xiaoyan Zhang Jianqing Xu |
| author_facet | Xinci Xie Chen Zhao Qian He Tianyi Qiu Songhua Yuan Longfei Ding Lu Liu Lang Jiang Jing Wang Linxia Zhang Chao Zhang Xiang Wang Dongming Zhou Xiaoyan Zhang Jianqing Xu |
| author_sort | Xinci Xie |
| collection | DOAJ |
| description | Given that continuing antigenic shift and drift of influenza A viruses result in the escape from previous vaccine-induced immune protection, a universal influenza vaccine has been actively sought. However, there were very few vaccines capable of eliciting cross-group ant-influenza immunity. Here, we designed two novel composite immunogens containing highly conserved T-cell epitopes of six influenza A virus internal antigens, and expressed them in DNA, recombinant adenovirus-based (AdC68) and recombinant vaccinia vectors, respectively, to formulate three vaccine forms. The introduction of the two immunogens via a DNA priming and viral vectored vaccine boosting modality afforded cross-group protection from both PR8 and H7N9 influenza virus challenges in mice. Both respiratory residential and systemic T cells contributed to the protective efficacy. Intranasal but not intramuscular administration of AdC68 based vaccine was capable of raising both T cell subpopulations to confer a full protection from lethal PR8 and H7N9 challenges, and blocking the lymphatic egress of T cells during challenges attenuated the protection. Thus, by targeting highly conserved internal viral epitopes to efficiently generate both respiratory and systemic memory T cells, the sequential vaccination strategy reported here represented a new promising candidate for the development of T-cell based universal influenza vaccines. |
| first_indexed | 2024-04-13T03:33:51Z |
| format | Article |
| id | doaj.art-77be8fb5ace043d9b695b4001648f06a |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-04-13T03:33:51Z |
| publishDate | 2019-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-77be8fb5ace043d9b695b4001648f06a2022-12-22T03:04:23ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2019-07-011010.3389/fmicb.2019.01630470811Influenza Vaccine With Consensus Internal Antigens as Immunogens Provides Cross-Group Protection Against Influenza A VirusesXinci Xie0Chen Zhao1Qian He2Tianyi Qiu3Songhua Yuan4Longfei Ding5Lu Liu6Lang Jiang7Jing Wang8Linxia Zhang9Chao Zhang10Xiang Wang11Dongming Zhou12Xiaoyan Zhang13Jianqing Xu14Shanghai Public Health Clinical Center and Institutes of Biomedical Science, Shanghai Medical College, Fudan University, Shanghai, ChinaShanghai Public Health Clinical Center and Institutes of Biomedical Science, Shanghai Medical College, Fudan University, Shanghai, ChinaShanghai Public Health Clinical Center and Institutes of Biomedical Science, Shanghai Medical College, Fudan University, Shanghai, ChinaShanghai Public Health Clinical Center and Institutes of Biomedical Science, Shanghai Medical College, Fudan University, Shanghai, ChinaShanghai Public Health Clinical Center and Institutes of Biomedical Science, Shanghai Medical College, Fudan University, Shanghai, ChinaShanghai Public Health Clinical Center and Institutes of Biomedical Science, Shanghai Medical College, Fudan University, Shanghai, ChinaShanghai Public Health Clinical Center and Institutes of Biomedical Science, Shanghai Medical College, Fudan University, Shanghai, ChinaShanghai Public Health Clinical Center and Institutes of Biomedical Science, Shanghai Medical College, Fudan University, Shanghai, ChinaShanghai Public Health Clinical Center and Institutes of Biomedical Science, Shanghai Medical College, Fudan University, Shanghai, ChinaShanghai Public Health Clinical Center and Institutes of Biomedical Science, Shanghai Medical College, Fudan University, Shanghai, ChinaVaccine Research Center, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, ChinaVaccine Research Center, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, ChinaVaccine Research Center, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, ChinaShanghai Public Health Clinical Center and Institutes of Biomedical Science, Shanghai Medical College, Fudan University, Shanghai, ChinaShanghai Public Health Clinical Center and Institutes of Biomedical Science, Shanghai Medical College, Fudan University, Shanghai, ChinaGiven that continuing antigenic shift and drift of influenza A viruses result in the escape from previous vaccine-induced immune protection, a universal influenza vaccine has been actively sought. However, there were very few vaccines capable of eliciting cross-group ant-influenza immunity. Here, we designed two novel composite immunogens containing highly conserved T-cell epitopes of six influenza A virus internal antigens, and expressed them in DNA, recombinant adenovirus-based (AdC68) and recombinant vaccinia vectors, respectively, to formulate three vaccine forms. The introduction of the two immunogens via a DNA priming and viral vectored vaccine boosting modality afforded cross-group protection from both PR8 and H7N9 influenza virus challenges in mice. Both respiratory residential and systemic T cells contributed to the protective efficacy. Intranasal but not intramuscular administration of AdC68 based vaccine was capable of raising both T cell subpopulations to confer a full protection from lethal PR8 and H7N9 challenges, and blocking the lymphatic egress of T cells during challenges attenuated the protection. Thus, by targeting highly conserved internal viral epitopes to efficiently generate both respiratory and systemic memory T cells, the sequential vaccination strategy reported here represented a new promising candidate for the development of T-cell based universal influenza vaccines.https://www.frontiersin.org/article/10.3389/fmicb.2019.01630/fulluniversal influenza vaccineconsensus sequenceCD8+ T cell epitopecross-protectionlung residential T cells |
| spellingShingle | Xinci Xie Chen Zhao Qian He Tianyi Qiu Songhua Yuan Longfei Ding Lu Liu Lang Jiang Jing Wang Linxia Zhang Chao Zhang Xiang Wang Dongming Zhou Xiaoyan Zhang Jianqing Xu Influenza Vaccine With Consensus Internal Antigens as Immunogens Provides Cross-Group Protection Against Influenza A Viruses Frontiers in Microbiology universal influenza vaccine consensus sequence CD8+ T cell epitope cross-protection lung residential T cells |
| title | Influenza Vaccine With Consensus Internal Antigens as Immunogens Provides Cross-Group Protection Against Influenza A Viruses |
| title_full | Influenza Vaccine With Consensus Internal Antigens as Immunogens Provides Cross-Group Protection Against Influenza A Viruses |
| title_fullStr | Influenza Vaccine With Consensus Internal Antigens as Immunogens Provides Cross-Group Protection Against Influenza A Viruses |
| title_full_unstemmed | Influenza Vaccine With Consensus Internal Antigens as Immunogens Provides Cross-Group Protection Against Influenza A Viruses |
| title_short | Influenza Vaccine With Consensus Internal Antigens as Immunogens Provides Cross-Group Protection Against Influenza A Viruses |
| title_sort | influenza vaccine with consensus internal antigens as immunogens provides cross group protection against influenza a viruses |
| topic | universal influenza vaccine consensus sequence CD8+ T cell epitope cross-protection lung residential T cells |
| url | https://www.frontiersin.org/article/10.3389/fmicb.2019.01630/full |
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