Development of a novel adenovirus type 4 vector as a promising respiratory vaccine vehicle
IntroductionAdenovirus (Ad) vectors are widely used for gene delivery, and some of them have been approved for vaccine development. In particular, the recombinant COVID-19 vaccine for inhalation, which was developed using adenovirus type 5 (Ad5), represents a milestone in respiratory immunization. O...
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Frontiers Media S.A.
2025-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1572081/full |
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| author | Jinghan Xu Busen Wang Zhenghao Zhao Shipo Wu Zhe Zhang Shuling Liu Nan Huo Wanru Zheng Yi Chen Zhiqiang Gao Zuyuan Jia Tianyu Liu Li Zhu Lihua Hou |
| author_facet | Jinghan Xu Busen Wang Zhenghao Zhao Shipo Wu Zhe Zhang Shuling Liu Nan Huo Wanru Zheng Yi Chen Zhiqiang Gao Zuyuan Jia Tianyu Liu Li Zhu Lihua Hou |
| author_sort | Jinghan Xu |
| collection | DOAJ |
| description | IntroductionAdenovirus (Ad) vectors are widely used for gene delivery, and some of them have been approved for vaccine development. In particular, the recombinant COVID-19 vaccine for inhalation, which was developed using adenovirus type 5 (Ad5), represents a milestone in respiratory immunization. Owing to the high pre-existing immunity (PEI) to Ad5, the development of an adenoviral vector with lower PEI and higher immunogenicity has been explored. However, the majority of the developed novel Ad vectors showed suboptimal immunogenicity compared to Ad5 in animal models.MethodIn this study, we constructed a novel replication-deficient viral vector based on human adenovirus type 4 (Ad4), which has long been used as a live virus vaccine with a favorable safety profile in the U.S. military. The mice were immunized intramuscularly or intranasally with an Ad4-vectored vaccine to verify immune responses and protective efficacy.ResultsCompared with Ad5, the novel Ad4 vector showed comparable viral growth kinetics and transgene expression in cells and similar exogenous protein expression and distribution in mice. Furthermore, the Ad4-vectored vaccine elicited superior humoral and cellular responses and protective effects when vaccinated intranasally than those triggered by the Ad5-vectored vaccine. Finally, the heterologous Ad5 prime and Ad4 boost immunization showed better immunogenicity and protective efficacy.DiscussionThis study broadens the research trajectory of adenovirus-vectored vaccines and offers a new option for the development of recombinant viral-vectored vaccines. |
| format | Article |
| id | doaj-art-e2bcd32016c04d708702ea0ffc24c81d |
| institution | DOAJ |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-e2bcd32016c04d708702ea0ffc24c81d2025-08-20T03:08:37ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-04-011610.3389/fimmu.2025.15720811572081Development of a novel adenovirus type 4 vector as a promising respiratory vaccine vehicleJinghan XuBusen WangZhenghao ZhaoShipo WuZhe ZhangShuling LiuNan HuoWanru ZhengYi ChenZhiqiang GaoZuyuan JiaTianyu LiuLi ZhuLihua HouIntroductionAdenovirus (Ad) vectors are widely used for gene delivery, and some of them have been approved for vaccine development. In particular, the recombinant COVID-19 vaccine for inhalation, which was developed using adenovirus type 5 (Ad5), represents a milestone in respiratory immunization. Owing to the high pre-existing immunity (PEI) to Ad5, the development of an adenoviral vector with lower PEI and higher immunogenicity has been explored. However, the majority of the developed novel Ad vectors showed suboptimal immunogenicity compared to Ad5 in animal models.MethodIn this study, we constructed a novel replication-deficient viral vector based on human adenovirus type 4 (Ad4), which has long been used as a live virus vaccine with a favorable safety profile in the U.S. military. The mice were immunized intramuscularly or intranasally with an Ad4-vectored vaccine to verify immune responses and protective efficacy.ResultsCompared with Ad5, the novel Ad4 vector showed comparable viral growth kinetics and transgene expression in cells and similar exogenous protein expression and distribution in mice. Furthermore, the Ad4-vectored vaccine elicited superior humoral and cellular responses and protective effects when vaccinated intranasally than those triggered by the Ad5-vectored vaccine. Finally, the heterologous Ad5 prime and Ad4 boost immunization showed better immunogenicity and protective efficacy.DiscussionThis study broadens the research trajectory of adenovirus-vectored vaccines and offers a new option for the development of recombinant viral-vectored vaccines.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1572081/fulladenovirusviral vectorvaccinemucosal immunityimmune response |
| spellingShingle | Jinghan Xu Busen Wang Zhenghao Zhao Shipo Wu Zhe Zhang Shuling Liu Nan Huo Wanru Zheng Yi Chen Zhiqiang Gao Zuyuan Jia Tianyu Liu Li Zhu Lihua Hou Development of a novel adenovirus type 4 vector as a promising respiratory vaccine vehicle Frontiers in Immunology adenovirus viral vector vaccine mucosal immunity immune response |
| title | Development of a novel adenovirus type 4 vector as a promising respiratory vaccine vehicle |
| title_full | Development of a novel adenovirus type 4 vector as a promising respiratory vaccine vehicle |
| title_fullStr | Development of a novel adenovirus type 4 vector as a promising respiratory vaccine vehicle |
| title_full_unstemmed | Development of a novel adenovirus type 4 vector as a promising respiratory vaccine vehicle |
| title_short | Development of a novel adenovirus type 4 vector as a promising respiratory vaccine vehicle |
| title_sort | development of a novel adenovirus type 4 vector as a promising respiratory vaccine vehicle |
| topic | adenovirus viral vector vaccine mucosal immunity immune response |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1572081/full |
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