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Safety, Immunogenicity and Efficacy of Heterologous Boost with an Aerosolized Ad5-nCoV after Two-Dose Priming with Inactivated COVID-19 Vaccines in Adults: A Multicenter, Open-Label Trial

25 Pages Posted: 7 Apr 2023

See all articles by Jing-Xin Li

Jing-Xin Li

Jiangsu Provincial Center for Disease Control and Prevention - NHC Key Laboratory of Enteric Pathogenic Microbiology

Li-Hua Hou

Academy of Military Medical Sciences - Institute of Biotechnology

Jin-Bo Gou

CanSino Biologics Inc.

Si-Yue Jia

Jiangsu Provincial Center for Disease Control and Prevention - NHC Key Laboratory of Enteric Pathogenic Microbiology

Zun-Dong Yin

Chinese Center for Disease Control and Prevention (China CDC) - National Immunization Program

Rong Tang

Jiangsu Provincial Center for Disease Control and Prevention - NHC Key Laboratory of Enteric Pathogenic Microbiology

Shi-Po Wu

Academy of Military Medical Sciences - Institute of Biotechnology

Fu-Zhen Wang

Chinese Center for Disease Control and Prevention (China CDC)

Zhe Zhang

Academy of Military Medical Sciences - Institute of Biotechnology

Hong-Xing Pan

Jiangsu Provincial Center for Disease Control and Prevention - NHC Key Laboratory of Enteric Pathogenic Microbiology

Li Zhang

Government of the People's Republic of China - Center of Disease Control and Prevention

Jia-Wei Xu

Chongqing Center for Disease Control and Prevention

Zhi-Hang Peng

Nanjing Medical University - School of Public Health

Ji-Hai Tang

Anhui Provincial Center for Disease Control and Prevention

Qing Wang

Chongqing Center for Disease Control and Prevention

Qing Xu

Anhui Provincial Center for Disease Control and Prevention

Yan Zheng

Yunan Provincial Center for Disease Control and Prevention

Tao Huang

Hunan Provincial Center for Disease Control and Prevention

Tao Li

Anhui Provincial Center for Disease Control and Prevention

Shu-Jun Liu

Hunan Provincial Center for Disease Control and Prevention

Cang-Ning Wang

Yunan Provincial Center for Disease Control and Prevention

Tao Zhu

CanSino Biologics Inc.

Hong-Bing Shen

Nanjing Medical University - Department of Epidemiology and Biostatistics

Wei Chen

Academy of Military Medical Sciences - Institute of Biotechnology

Feng-Cai Zhu

Jiangsu Provincial Center for Disease Control and Prevention - NHC Key Laboratory of Enteric Pathogenic Microbiology

More...

Abstract

Background: The aerosolized Ad5-nCoV is the first licensed mucosal respiratory vaccine against SARS-CoV-2 in the word. The safety and efficacy of the aerosolized Ad5-nCoV in large population has not been reported yet.

Methods: This is a multicenter, open-label trial, aiming to evaluate the safety and immunogenicity with aerosolized Ad5-nCoV in health adults ≥18 years of age, who had received two priming doses of Inactivated COVID-19 vaccine. Of them, at least 30% were equal to or over 60 years of age. This study contains a non-randomized safety cohort, and a randomized, parallel-controlled immunogenicity sub-cohort. The primary endpoints were the incidence of adverse reactions following the booster vaccination with aerosolized Ad5-nCoV and the levels of neutralizing antibodies at day 28 post-boost.

Findings: A total of 10059 participants who were boosted with the aerosolized Ad5-nCoV were involved in the safety analysis, while 416 participants were involved immunogenicity analysis. Adverse reactions were reported by 1299 (12.9%) participants within 28 days after receiving the booster vaccination with aerosolized Ad5-nCoV, but most of the adverse reactions reported were mild to moderate in severity. Participants receiving aerosolized Ad5-nCoV showed significantly higher level of the neutralizing antibodies against omicron BA.4/5 than those receiving inactivated vaccine at day 28 (107.7[95%CI 88.8-130.7] versus 17.2[95%CI 16.3-18.2]). The overall relative efficacy of the aerosolized Ad5-nCoV versus inactivated vaccine was 35.1% (95%CI 23.0-45.2) at about 12 months after the immunization.

Interpretation: The heterologous booster regimen with aerosolized Ad5-nCoV is safe and highly immunogenic, and provided a long-term protection against Omicron variants (ClinicalTrials.gov, NCT05204589).

Trial Registration: The study is registered at ClinicalTrials.gov, NCT05204589.

Funding: This work is funded by National Natural Science Foundation of China (grant number 82173584 and 82222062), Jiangsu Provincial Science Fund for Distinguished Young Scholars (grant number BK20220064), and Jiangsu Provincial Key Project of Science and Technology Plan (grant number BE2021738). CanSino Biologics Inc. contributed in providing investigational vaccines and the vapouring unit (Aerogen, Galway, Ireland) integrated by Suzhou Weiqi Biological Technology (Suzhou City, China) were used for this study.

Declaration of Interest: Jin-Bo Gou, and Tao Zhu are employees of CanSino Biologics. All the other authors declare no competing interests.

Ethical Approval: The trial was reviewed and approved by the Scientific Review Committee and the Ethics Committee of Jiangsu Provincial Center for Disease Control and Prevention. All the participants provided written informed consent before enrollment. The trial adhered to the principles of the Declaration of Helsinki, International Council for Harmonisation-Good Clinical Practice guidelines, and local guidelines.

Keywords: Safety, Immunogenicity, Long-term efficacy, Aerosolized Ad5-nCoV, Booster

Suggested Citation

Li, Jing-Xin and Hou, Li-Hua and Gou, Jin-Bo and Jia, Si-Yue and Yin, Zun-Dong and Tang, Rong and Wu, Shi-Po and Wang, Fu-Zhen and Zhang, Zhe and Pan, Hong-Xing and Zhang, Li and Xu, Jia-Wei and Peng, Zhi-Hang and Tang, Ji-Hai and Wang, Qing and Xu, Qing and Zheng, Yan and Huang, Tao and Li, Tao and Liu, Shu-Jun and Wang, Cang-Ning and Zhu, Tao and Shen, Hong-Bing and Chen, Wei and Zhu, Feng-Cai, Safety, Immunogenicity and Efficacy of Heterologous Boost with an Aerosolized Ad5-nCoV after Two-Dose Priming with Inactivated COVID-19 Vaccines in Adults: A Multicenter, Open-Label Trial. Available at SSRN: https://ssrn.com/abstract=4409350 or http://dx.doi.org/10.2139/ssrn.4409350

Jing-Xin Li

Jiangsu Provincial Center for Disease Control and Prevention - NHC Key Laboratory of Enteric Pathogenic Microbiology ( email )

Li-Hua Hou

Academy of Military Medical Sciences - Institute of Biotechnology ( email )

Beijing
China

Jin-Bo Gou

CanSino Biologics Inc. ( email )

Tianjin
China

Si-Yue Jia

Jiangsu Provincial Center for Disease Control and Prevention - NHC Key Laboratory of Enteric Pathogenic Microbiology ( email )

Zun-Dong Yin

Chinese Center for Disease Control and Prevention (China CDC) - National Immunization Program ( email )

155 Changbai Road
Changping District
Beijing, Changping District 102206
China

Rong Tang

Jiangsu Provincial Center for Disease Control and Prevention - NHC Key Laboratory of Enteric Pathogenic Microbiology ( email )

Nanjing
China

Shi-Po Wu

Academy of Military Medical Sciences - Institute of Biotechnology ( email )

Beijing
China

Fu-Zhen Wang

Chinese Center for Disease Control and Prevention (China CDC) ( email )

Zhe Zhang

Academy of Military Medical Sciences - Institute of Biotechnology

Hong-Xing Pan

Jiangsu Provincial Center for Disease Control and Prevention - NHC Key Laboratory of Enteric Pathogenic Microbiology ( email )

Nanjing
China

Li Zhang

Government of the People's Republic of China - Center of Disease Control and Prevention ( email )

Jia-Wei Xu

Chongqing Center for Disease Control and Prevention ( email )

Zhi-Hang Peng

Nanjing Medical University - School of Public Health ( email )

Ji-Hai Tang

Anhui Provincial Center for Disease Control and Prevention ( email )

Hefei, 12560
China

Qing Wang

Chongqing Center for Disease Control and Prevention ( email )

Qing Xu

Anhui Provincial Center for Disease Control and Prevention ( email )

Yan Zheng

Yunan Provincial Center for Disease Control and Prevention ( email )

Tao Huang

Hunan Provincial Center for Disease Control and Prevention ( email )

Tao Li

Anhui Provincial Center for Disease Control and Prevention ( email )

Hefei, 12560
China

Shu-Jun Liu

Hunan Provincial Center for Disease Control and Prevention ( email )

Changsha
China

Cang-Ning Wang

Yunan Provincial Center for Disease Control and Prevention ( email )

Tao Zhu

CanSino Biologics Inc. ( email )

Tianjin
China

Hong-Bing Shen

Nanjing Medical University - Department of Epidemiology and Biostatistics ( email )

Wei Chen

Academy of Military Medical Sciences - Institute of Biotechnology ( email )

Beijing
China

Feng-Cai Zhu (Contact Author)

Jiangsu Provincial Center for Disease Control and Prevention - NHC Key Laboratory of Enteric Pathogenic Microbiology ( email )

Nanjing
China

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