tetano
Editor, Senior Moderator
Nat Commun
. 2025 Aug 7;16(1):7281.
doi: 10.1038/s41467-025-62698-7. Safety and Immunogenicity of aerosolized adenovirus-vectored COVID-19 vaccine and intramuscular mRNA vaccine bivalent boosters: a randomized open-label clinical trial
Shipo Wu[SUP] #[/SUP][SUP] 1 [/SUP], Jianying Huang[SUP] #[/SUP][SUP] 2 [/SUP], Busen Wang[SUP] #[/SUP][SUP] 1 [/SUP], Jianhua Li[SUP] #[/SUP][SUP] 3 [/SUP], Jianyuan Wu[SUP] 2 [/SUP], Zhe Zhang[SUP] 1 [/SUP], Lin Luo[SUP] 2 [/SUP], Jinlong Zhang[SUP] 1 [/SUP], Nan Huo[SUP] 1 [/SUP], Jianglan Long[SUP] 1 [/SUP], He Huang[SUP] 1 [/SUP], Zhengshan Chen[SUP] 1 [/SUP], Mengyao Zhang[SUP] 1 [/SUP], Zhenghao Zhao[SUP] 1 [/SUP], Junyan Dan[SUP] 1 [/SUP], Xiaohong Song[SUP] 1 [/SUP], Haiyan Mao[SUP] 3 [/SUP], Shengyuan Huo[SUP] 1 [/SUP], Hao Yan[SUP] 3 [/SUP], Yanjun Zhang[SUP] 4 [/SUP], Xinghuan Wang[SUP] 5 6 [/SUP], Lihua Hou[SUP] 7 [/SUP]
Affiliations
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.
. 2025 Aug 7;16(1):7281.
doi: 10.1038/s41467-025-62698-7. Safety and Immunogenicity of aerosolized adenovirus-vectored COVID-19 vaccine and intramuscular mRNA vaccine bivalent boosters: a randomized open-label clinical trial
Shipo Wu[SUP] #[/SUP][SUP] 1 [/SUP], Jianying Huang[SUP] #[/SUP][SUP] 2 [/SUP], Busen Wang[SUP] #[/SUP][SUP] 1 [/SUP], Jianhua Li[SUP] #[/SUP][SUP] 3 [/SUP], Jianyuan Wu[SUP] 2 [/SUP], Zhe Zhang[SUP] 1 [/SUP], Lin Luo[SUP] 2 [/SUP], Jinlong Zhang[SUP] 1 [/SUP], Nan Huo[SUP] 1 [/SUP], Jianglan Long[SUP] 1 [/SUP], He Huang[SUP] 1 [/SUP], Zhengshan Chen[SUP] 1 [/SUP], Mengyao Zhang[SUP] 1 [/SUP], Zhenghao Zhao[SUP] 1 [/SUP], Junyan Dan[SUP] 1 [/SUP], Xiaohong Song[SUP] 1 [/SUP], Haiyan Mao[SUP] 3 [/SUP], Shengyuan Huo[SUP] 1 [/SUP], Hao Yan[SUP] 3 [/SUP], Yanjun Zhang[SUP] 4 [/SUP], Xinghuan Wang[SUP] 5 6 [/SUP], Lihua Hou[SUP] 7 [/SUP]
Affiliations
- PMID: 40775215
- DOI: 10.1038/s41467-025-62698-7
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.