A novel simian adenovirus-vectored COVID-19 vaccine elicits effective mucosal and systemic immunity in mice by intranasal and intramuscular vaccination regimens
ABSTRACT The failure of COVID-19 vaccines to prevent SARS-CoV-2 infection and transmission, a possibly critical reason was the lack of protective mucosal immunity in the respiratory tract. Here, we evaluated the effects of mucosal and systemic immunity from a novel simian adenovirus-vectored COVID-1...
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2023-12-01
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| Series: | Microbiology Spectrum |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.01794-23 |
| _version_ | 1797393638913736704 |
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| author | Panli Zhang Shengxue Luo Peng Zou Qitao Deng Cong Wang Jinfeng Li Peiqiao Cai Ling Zhang Chengyao Li Tingting Li |
| author_facet | Panli Zhang Shengxue Luo Peng Zou Qitao Deng Cong Wang Jinfeng Li Peiqiao Cai Ling Zhang Chengyao Li Tingting Li |
| author_sort | Panli Zhang |
| collection | DOAJ |
| description | ABSTRACT The failure of COVID-19 vaccines to prevent SARS-CoV-2 infection and transmission, a possibly critical reason was the lack of protective mucosal immunity in the respiratory tract. Here, we evaluated the effects of mucosal and systemic immunity from a novel simian adenovirus-vectored COVID-19 vaccine (Sad23L-nCoV-S) in mice in comparison with Ad5-nCoV-S by intranasal (IN) drip and intramuscular (IM) injection vaccinations. As good as the well-known Ad5-nCoV-S vaccine, a single-dose IN inoculation of 1 × 109 PFU Sad23L-nCoV-S vaccine induced a similar level of IgG S-binding antibody (S-BAb) and neutralizing antibody (NAb) and higher IgA in serum, while IN route raised significantly higher IgG and IgA S-BAb and NAb in bronchoalveolar lavage (BAL), and specific IFN-γ secreting T-cell response in lung compared with IM route, but lower T-cell response in spleen. By prime-boost vaccination regimens with different combinations of IN and IM inoculations of Sad23L-nCoV-S vaccine, the IN-involved vaccination stimulated higher protective mucosal or local immunity in BAL and lung, while the IM-involved immunization induced higher systemic immunity in serum and spleen. A long-term sustained mucosal and systemic NAb and T- cell immunity to SARS-CoV-2 was maintained at high level over 32 weeks by prime-boost vaccination regimens with IN and IM routes. In conclusion, priming or boosting immunization with IN inoculation of Sad23L-nCoV-S vaccine could induce effective mucosal immunity and in combination of IM route could additionally achieve systemic immunity, which provided an important reference for vaccination regimens against respiratory virus infection. IMPORTANCE The essential goal of vaccination is to generate potent and long-term protection against diseases. Several factors including vaccine vector, delivery route, and boosting regimen influence the outcome of prime-boost immunization approaches. The immunization regimens by constructing a novel simian adenovirus-vectored COVID-19 vaccine and employing combination of intranasal and intramuscular inoculations could elicit mucosal neutralizing antibodies against five mutant strains in the respiratory tract and strong systemic immunity. Immune protection could last for more than 32 weeks. Vectored vaccine construction and immunization regimens have positively impacted respiratory disease prevention. |
| first_indexed | 2024-03-09T00:06:43Z |
| format | Article |
| id | doaj.art-e8ef3981dfea44ec83fb843025ebb425 |
| institution | Directory Open Access Journal |
| issn | 2165-0497 |
| language | English |
| last_indexed | 2024-03-09T00:06:43Z |
| publishDate | 2023-12-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | Microbiology Spectrum |
| spelling | doaj.art-e8ef3981dfea44ec83fb843025ebb4252023-12-12T13:17:19ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972023-12-0111610.1128/spectrum.01794-23A novel simian adenovirus-vectored COVID-19 vaccine elicits effective mucosal and systemic immunity in mice by intranasal and intramuscular vaccination regimensPanli Zhang0Shengxue Luo1Peng Zou2Qitao Deng3Cong Wang4Jinfeng Li5Peiqiao Cai6Ling Zhang7Chengyao Li8Tingting Li9Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University , Guangzhou, ChinaDepartment of Pediatrics, Shenzhen Hospital, Southern Medical University , Shenzhen, ChinaDepartment of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University , Guangzhou, ChinaDepartment of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University , Guangzhou, ChinaDepartment of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University , Guangzhou, ChinaShenzhen Bao'an District Central Blood Station , Shenzhen, ChinaDepartment of Bioengineering, School of Medicine and College of Engineering, University of Washington , Seattle, Washington, USADepartment of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University , Guangzhou, ChinaDepartment of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University , Guangzhou, ChinaDepartment of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University , Guangzhou, ChinaABSTRACT The failure of COVID-19 vaccines to prevent SARS-CoV-2 infection and transmission, a possibly critical reason was the lack of protective mucosal immunity in the respiratory tract. Here, we evaluated the effects of mucosal and systemic immunity from a novel simian adenovirus-vectored COVID-19 vaccine (Sad23L-nCoV-S) in mice in comparison with Ad5-nCoV-S by intranasal (IN) drip and intramuscular (IM) injection vaccinations. As good as the well-known Ad5-nCoV-S vaccine, a single-dose IN inoculation of 1 × 109 PFU Sad23L-nCoV-S vaccine induced a similar level of IgG S-binding antibody (S-BAb) and neutralizing antibody (NAb) and higher IgA in serum, while IN route raised significantly higher IgG and IgA S-BAb and NAb in bronchoalveolar lavage (BAL), and specific IFN-γ secreting T-cell response in lung compared with IM route, but lower T-cell response in spleen. By prime-boost vaccination regimens with different combinations of IN and IM inoculations of Sad23L-nCoV-S vaccine, the IN-involved vaccination stimulated higher protective mucosal or local immunity in BAL and lung, while the IM-involved immunization induced higher systemic immunity in serum and spleen. A long-term sustained mucosal and systemic NAb and T- cell immunity to SARS-CoV-2 was maintained at high level over 32 weeks by prime-boost vaccination regimens with IN and IM routes. In conclusion, priming or boosting immunization with IN inoculation of Sad23L-nCoV-S vaccine could induce effective mucosal immunity and in combination of IM route could additionally achieve systemic immunity, which provided an important reference for vaccination regimens against respiratory virus infection. IMPORTANCE The essential goal of vaccination is to generate potent and long-term protection against diseases. Several factors including vaccine vector, delivery route, and boosting regimen influence the outcome of prime-boost immunization approaches. The immunization regimens by constructing a novel simian adenovirus-vectored COVID-19 vaccine and employing combination of intranasal and intramuscular inoculations could elicit mucosal neutralizing antibodies against five mutant strains in the respiratory tract and strong systemic immunity. Immune protection could last for more than 32 weeks. Vectored vaccine construction and immunization regimens have positively impacted respiratory disease prevention.https://journals.asm.org/doi/10.1128/spectrum.01794-23adenoviral vectorintranasal immunizationmucosal immunityrespiratory virusvaccination regimen |
| spellingShingle | Panli Zhang Shengxue Luo Peng Zou Qitao Deng Cong Wang Jinfeng Li Peiqiao Cai Ling Zhang Chengyao Li Tingting Li A novel simian adenovirus-vectored COVID-19 vaccine elicits effective mucosal and systemic immunity in mice by intranasal and intramuscular vaccination regimens Microbiology Spectrum adenoviral vector intranasal immunization mucosal immunity respiratory virus vaccination regimen |
| title | A novel simian adenovirus-vectored COVID-19 vaccine elicits effective mucosal and systemic immunity in mice by intranasal and intramuscular vaccination regimens |
| title_full | A novel simian adenovirus-vectored COVID-19 vaccine elicits effective mucosal and systemic immunity in mice by intranasal and intramuscular vaccination regimens |
| title_fullStr | A novel simian adenovirus-vectored COVID-19 vaccine elicits effective mucosal and systemic immunity in mice by intranasal and intramuscular vaccination regimens |
| title_full_unstemmed | A novel simian adenovirus-vectored COVID-19 vaccine elicits effective mucosal and systemic immunity in mice by intranasal and intramuscular vaccination regimens |
| title_short | A novel simian adenovirus-vectored COVID-19 vaccine elicits effective mucosal and systemic immunity in mice by intranasal and intramuscular vaccination regimens |
| title_sort | novel simian adenovirus vectored covid 19 vaccine elicits effective mucosal and systemic immunity in mice by intranasal and intramuscular vaccination regimens |
| topic | adenoviral vector intranasal immunization mucosal immunity respiratory virus vaccination regimen |
| url | https://journals.asm.org/doi/10.1128/spectrum.01794-23 |
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