Safety and Immunogenicity of aerosolized adenovirus-vectored COVID-19 vaccine and intramuscular mRNA vaccine bivalent boosters: a randomized open-label clinical trial
Abstract Both SARS-CoV-2 mRNA and mucosal vaccines induce protective immunity against COVID-19 but showed different immune profiles. We conducted a longitudinal head-to-head analysis of the safety and immunogenicity of the aerosolized adenovirus-vectored and mRNA COVID-19 vaccines. 450 participants...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-08-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-62698-7 |
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| author | Shipo Wu Jianying Huang Busen Wang Jianhua Li Jianyuan Wu Zhe Zhang Lin Luo Jinlong Zhang Nan Huo Jianglan Long He Huang Zhengshan Chen Mengyao Zhang Zhenghao Zhao Junyan Dan Xiaohong Song Haiyan Mao Shengyuan Huo Hao Yan Yanjun Zhang Xinghuan Wang Lihua Hou |
| author_facet | Shipo Wu Jianying Huang Busen Wang Jianhua Li Jianyuan Wu Zhe Zhang Lin Luo Jinlong Zhang Nan Huo Jianglan Long He Huang Zhengshan Chen Mengyao Zhang Zhenghao Zhao Junyan Dan Xiaohong Song Haiyan Mao Shengyuan Huo Hao Yan Yanjun Zhang Xinghuan Wang Lihua Hou |
| author_sort | Shipo Wu |
| collection | DOAJ |
| description | Abstract Both SARS-CoV-2 mRNA and mucosal vaccines induce protective immunity against COVID-19 but showed different immune profiles. We conducted a longitudinal head-to-head analysis of the safety and immunogenicity of the aerosolized adenovirus-vectored and mRNA COVID-19 vaccines. 450 participants were enrolled and randomly assigned into three groups to be vaccinated with an aerosolized Ad5-vectored bivalent vaccine (wild-type and BA.5, Ad5-CoV5T), an intramuscular bivalent mRNA vaccine (mbO5), and an aerosolized wild-type Ad5-vectored vaccine (Ad5-nCoV). The primary outcomes were adverse reactions within 28 days and anti-XBB.1.5-specific neutralizing antibody titers at day 28 after vaccination. The secondary outcome assessed safety within 30 min, serious adverse event within 6 months, and the persistence of anti-XBB.1.5/BA.5-specific neutralizing antibodies during the 6 months. Both the vaccines were well tolerated, but participants vaccinated with mbO5 reported more adverse reactions (73.3% mbO5 vaccinees vs. 28.7% aerosol vaccinees). No serious adverse events were recorded. The Ad5-CoV5T vaccine induced a superior anti-XBB.1.5-specific neutralizing titer than Ad5-nCoV at day 28 (geometric mean titer ratio of 1.48, 95% CI 1.12–1.97), while the mbO5 vaccine induced the highest antibody titer. The neutralizing antibodies were declined at month 6 and were similar across the three groups. In the pre-specified exploratory analysis, the mbO5 and the aerosolized vaccines induced comparable antigen-specific memory B cells but the latter stimulated higher frequency of IgA isotype and higher expression of CXCR3. This trial met the main hypothesis; the findings may provide insights for the development of the next-generation COVID-19 vaccines. Clinical Trials.gov identifier: NCT05886790. |
| format | Article |
| id | doaj-art-e96f24faae34412fb21a05d7e360de95 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-e96f24faae34412fb21a05d7e360de952025-08-20T03:43:27ZengNature PortfolioNature Communications2041-17232025-08-0116111510.1038/s41467-025-62698-7Safety and Immunogenicity of aerosolized adenovirus-vectored COVID-19 vaccine and intramuscular mRNA vaccine bivalent boosters: a randomized open-label clinical trialShipo Wu0Jianying Huang1Busen Wang2Jianhua Li3Jianyuan Wu4Zhe Zhang5Lin Luo6Jinlong Zhang7Nan Huo8Jianglan Long9He Huang10Zhengshan Chen11Mengyao Zhang12Zhenghao Zhao13Junyan Dan14Xiaohong Song15Haiyan Mao16Shengyuan Huo17Hao Yan18Yanjun Zhang19Xinghuan Wang20Lihua Hou21Laboratory of Advanced Biotechnology, Beijing Institute of BiotechnologyClinical Trial Center, Zhongnan Hospital of Wuhan UniversityLaboratory of Advanced Biotechnology, Beijing Institute of BiotechnologyDepartment of Microbiology, Zhejiang Key Laboratory of Public Health Detection and Pathogenesis Research, Zhejiang Provincial Center for Disease Control and PreventionClinical Trial Center, Zhongnan Hospital of Wuhan UniversityLaboratory of Advanced Biotechnology, Beijing Institute of BiotechnologyClinical Trial Center, Zhongnan Hospital of Wuhan UniversityLaboratory of Advanced Biotechnology, Beijing Institute of BiotechnologyLaboratory of Advanced Biotechnology, Beijing Institute of BiotechnologyLaboratory of Advanced Biotechnology, Beijing Institute of BiotechnologyLaboratory of Advanced Biotechnology, Beijing Institute of BiotechnologyLaboratory of Advanced Biotechnology, Beijing Institute of BiotechnologyLaboratory of Advanced Biotechnology, Beijing Institute of BiotechnologyLaboratory of Advanced Biotechnology, Beijing Institute of BiotechnologyLaboratory of Advanced Biotechnology, Beijing Institute of BiotechnologyLaboratory of Advanced Biotechnology, Beijing Institute of BiotechnologyDepartment of Microbiology, Zhejiang Key Laboratory of Public Health Detection and Pathogenesis Research, Zhejiang Provincial Center for Disease Control and PreventionLaboratory of Advanced Biotechnology, Beijing Institute of BiotechnologyDepartment of Microbiology, Zhejiang Key Laboratory of Public Health Detection and Pathogenesis Research, Zhejiang Provincial Center for Disease Control and PreventionDepartment of Microbiology, Zhejiang Key Laboratory of Public Health Detection and Pathogenesis Research, Zhejiang Provincial Center for Disease Control and PreventionClinical Trial Center, Zhongnan Hospital of Wuhan UniversityLaboratory of Advanced Biotechnology, Beijing Institute of BiotechnologyAbstract Both SARS-CoV-2 mRNA and mucosal vaccines induce protective immunity against COVID-19 but showed different immune profiles. We conducted a longitudinal head-to-head analysis of the safety and immunogenicity of the aerosolized adenovirus-vectored and mRNA COVID-19 vaccines. 450 participants were enrolled and randomly assigned into three groups to be vaccinated with an aerosolized Ad5-vectored bivalent vaccine (wild-type and BA.5, Ad5-CoV5T), an intramuscular bivalent mRNA vaccine (mbO5), and an aerosolized wild-type Ad5-vectored vaccine (Ad5-nCoV). The primary outcomes were adverse reactions within 28 days and anti-XBB.1.5-specific neutralizing antibody titers at day 28 after vaccination. The secondary outcome assessed safety within 30 min, serious adverse event within 6 months, and the persistence of anti-XBB.1.5/BA.5-specific neutralizing antibodies during the 6 months. Both the vaccines were well tolerated, but participants vaccinated with mbO5 reported more adverse reactions (73.3% mbO5 vaccinees vs. 28.7% aerosol vaccinees). No serious adverse events were recorded. The Ad5-CoV5T vaccine induced a superior anti-XBB.1.5-specific neutralizing titer than Ad5-nCoV at day 28 (geometric mean titer ratio of 1.48, 95% CI 1.12–1.97), while the mbO5 vaccine induced the highest antibody titer. The neutralizing antibodies were declined at month 6 and were similar across the three groups. In the pre-specified exploratory analysis, the mbO5 and the aerosolized vaccines induced comparable antigen-specific memory B cells but the latter stimulated higher frequency of IgA isotype and higher expression of CXCR3. This trial met the main hypothesis; the findings may provide insights for the development of the next-generation COVID-19 vaccines. Clinical Trials.gov identifier: NCT05886790.https://doi.org/10.1038/s41467-025-62698-7 |
| spellingShingle | Shipo Wu Jianying Huang Busen Wang Jianhua Li Jianyuan Wu Zhe Zhang Lin Luo Jinlong Zhang Nan Huo Jianglan Long He Huang Zhengshan Chen Mengyao Zhang Zhenghao Zhao Junyan Dan Xiaohong Song Haiyan Mao Shengyuan Huo Hao Yan Yanjun Zhang Xinghuan Wang Lihua Hou Safety and Immunogenicity of aerosolized adenovirus-vectored COVID-19 vaccine and intramuscular mRNA vaccine bivalent boosters: a randomized open-label clinical trial Nature Communications |
| title | Safety and Immunogenicity of aerosolized adenovirus-vectored COVID-19 vaccine and intramuscular mRNA vaccine bivalent boosters: a randomized open-label clinical trial |
| title_full | Safety and Immunogenicity of aerosolized adenovirus-vectored COVID-19 vaccine and intramuscular mRNA vaccine bivalent boosters: a randomized open-label clinical trial |
| title_fullStr | Safety and Immunogenicity of aerosolized adenovirus-vectored COVID-19 vaccine and intramuscular mRNA vaccine bivalent boosters: a randomized open-label clinical trial |
| title_full_unstemmed | Safety and Immunogenicity of aerosolized adenovirus-vectored COVID-19 vaccine and intramuscular mRNA vaccine bivalent boosters: a randomized open-label clinical trial |
| title_short | Safety and Immunogenicity of aerosolized adenovirus-vectored COVID-19 vaccine and intramuscular mRNA vaccine bivalent boosters: a randomized open-label clinical trial |
| title_sort | safety and immunogenicity of aerosolized adenovirus vectored covid 19 vaccine and intramuscular mrna vaccine bivalent boosters a randomized open label clinical trial |
| url | https://doi.org/10.1038/s41467-025-62698-7 |
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